Publicado

2022-04-01

Clinical Practice Guideline for the management of community-acquired pneumonia

Guía de práctica clínica para el manejo de la neumonía adquirida en la comunidad

DOI:

https://doi.org/10.15446/revfacmed.v70n2.93814

Palabras clave:

Clinical guidelines as Topic, Pneumonia, Respiratory tract infections, Community-Acquired Infections, Colombia (en)
Guías de Práctica Clínica como Asunto, Neumonía, Infecciones del sistema respiratorio, Infecciones comunitarias adquiridas, Colombia (es)

Autores/as

  • Jorge Alberto Cortés Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Hospital Universitario Nacional de Colombia - Comité de Infecciones Asociadas a la Atención en Salud - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-0882-9652
  • Sonia Isabel Cuervo-Maldonado Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. https://orcid.org/0000-0001-5676-880X
  • Laura Cristina Nocua-Báez Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-2869-2339
  • Martha Carolina Valderrama Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-4971-9692
  • Edgar Alberto Sánchez Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Hospital Universitario Nacional de Colombia - Unidad de Neumología - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-5518-8149
  • Alfredo Saavedra Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Hospital Universitario Nacional de Colombia - Unidad de Neumología - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-4292-803X
  • July Vianneth Torres Hospital Universitario Nacional de Colombia - Unidad de Neumología - Bogotá D.C. - Colombia. https://orcid.org/0000-0001-7311-2132
  • Diana Paola Forero Hospital Universitario Nacional de Colombia - Unidad de Neumología - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-9011-230X
  • Carlos Arturo Álvarez-Moreno Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. https://orcid.org/0000-0001-5419-4494
  • Aura Lucía Leal Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Microbiología - Bogotá D.C. - Colombia. | Fundación Santa Fe de Bogotá - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Fundación Santa Fe de Bogotá - Departamento de Patología y Laboratorios - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-3063-3821
  • Jairo Enrique Pérez Fundación Cardioinfantil - Instituto de Cardiología - Bogotá D.C. - Colombia. https://orcid.org/0000-0001-6009-4019
  • Iván Arturo Rodríguez Hospital San Vicente Fundación Rionegro - Rionegro - Colombia. https://orcid.org/0000-0002-5381-9816
  • Fredy Orlando Guevara Clínica Colsanitas - Clínica Reina Sofía - Departamento de Vigilancia, Control y Prevención de Enfermedades Infecciosas - Bogotá D.C. - Colombia. | Fundación Santa Fé de Bogotá - Sección de Enfermedades Infecciosas - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-6256-4130
  • Carlos Humberto Saavedra Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-0068-6631
  • Erika Paola Vergara Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Hospital Universitario Nacional de Colombia - Comité de Infecciones Asociadas a la Atención en Salud - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-5906-9593
  • Franco Eduardo Montúfar Universidad de Antioquia - Clínica León XIII - Medellín - Colombia. https://orcid.org/0000-0002-8491-6686
  • Tatiana Espinosa Clínica Cardiovascular del Caribe - Montería - Colombia. https://orcid.org/0000-0002-7296-9238
  • Walter Chaves Hospital de San José de Bogotá - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Fundación Universitaria de Ciencias de la Salud - Departamento de Medicina Interna - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-3446-9048
  • Jorge Armando Carrizosa Fundación Santa Fe de Bogotá - Unidad de Cuidado Neurocrítico - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-0412-5452
  • Sugeich Del Mar Meléndez Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Hospital Universitario Nacional de Colombia - Subdirección de Clínicas Médicas - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-4593-3125
  • Carmelo José Espinosa Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia. | Hospital Universitario Nacional de Colombia - Dirección de Cuidado Intensivo - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-9148-1289
  • Felipe García-López Hospital Universitario Nacional de Colombia - Departamento de Auditoría - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-2623-1689
  • Ingrid Jany Guzmán Hospital Universitario Nacional de Colombia - Dirección de Rehabilitación y Desarrollo Humano - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-2293-8617
  • Sergio Leonardo Cortés Hospital Universitario Nacional de Colombia - Dirección de Rehabilitación y Desarrollo Humano - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-8092-0813
  • Jorge Augusto Díaz Universidad Nacional de Colombia - Facultad de Ciencias - Departamento de Farmacia - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-0875-4846
  • Nathaly González Hospital Universitario Nacional de Colombia - Departamento de Enfermería - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-3486-7046

Pneumonia continues to be one of the main causes of consultation and hospitalization to which, besides its high impact on morbidity and mortality, the current problem of antimicrobial resistance is added; thus, establishing guidelines that allow its adequate diagnosis and treatment is of great importance to obtain better clinical outcomes and promote a rational use of antibiotics in these patients. This clinical practice guideline (CPG) contains evidence-based recommendations for the diagnosis and treatment of community-acquired pneumonia in adult population; these recommendations were made by means of the process of adaptation of evidence-based CPGs for the Colombian context.

La neumonía sigue siendo una de las principales causas de consulta y de hospitalización a la que, además de su un alto impacto en términos de morbilidad y mortalidad, se suma la actual problemática de resistencia a los antimicrobianos, por lo que establecer directrices que permitan su adecuado diagnóstico y tratamiento es de gran importancia para obtener mejores desenlaces clínicos y promover un uso racional de antibióticos en estos pacientes. La presente guía de práctica clínica (GPC) contiene recomendaciones basadas en la evidencia para el diagnóstico y tratamiento de la neumonía adquirida en la comunidad en adultos, las cuales fueron realizadas mediante el proceso de adaptación de GPC basadas en la evidencia para el contexto colombiano.

93814_En

Clinical practice guideline

Clinical practice guideline for the management of community-acquired pneumonia

Guía de práctica clínica para el manejo de la neumonía adquirida en la comunidad

Jorge Alberto Cortés1,2 Sonia Isabel Cuervo-Maldonado 1 Laura Cristina Nocua-Báez1 Martha Carolina Valderrama1 Edgar Alberto Sánchez1,3 Alfredo Saavedra1,3 July Vianneth Torres3 Diana Paola Forero3 Carlos Arturo Álvarez-Moreno1 Aura Lucía Leal4,5,6 Jairo Enrique Pérez7 Iván Arturo Rodríguez8 Fredy Orlando Guevara9,10 Carlos Humberto Saavedra1 Erika Paola Vergara1,2 Franco Eduardo Montúfar11 Tatiana Espinosa12 Walter Chaves13,14 Jorge Armando Carrizosa15 Sugeich Del Mar Meléndez1,16 Carmelo José Espinosa1,17 Felipe García-López18 Ingrid Jany Guzmán19 Sergio Leonardo Cortés19 Jorge Augusto Díaz20 Nathaly González21

1 Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Internal Medicine - Bogotá D.C. - Colombia.

2 Hospital Universitario Nacional de Colombia - Healthcare-Associated Infection Committee - Bogotá D.C. - Colombia.

3 Hospital Universitario Nacional de Colombia - Pulmonology Unit - Bogotá D.C. - Colombia.

4 Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Microbiology - Bogotá D.C. - Colombia.

5 Fundación Santa Fé de Bogotá - Department of Internal Medicine - Bogotá D.C. - Colombia.

6 Fundación Santa Fé de Bogotá - Department of Pathology and Clinical Laboratories - Bogotá D.C. - Colombia.

7 Fundación Cardioinfantil - Institute of Cardiology - Bogotá D.C. - Colombia.

8 Hospital San Vicente Fundación Rionegro - Rionegro - Colombia.

9 Clínica Colsanitas - Clínica Reina Sofía - Department of Surveillance, Control, and Prevention of Infectious Diseases - Bogotá D.C. - Colombia.

10 Fundación Santa Fé de Bogotá - Infectious Diseases Section - Bogotá D.C. - Colombia.

11 Universidad de Antioquia - Clínica León XIII - Medellín - Colombia.

12 Clínica Cardiovascular del Caribe - Montería - Colombia.

13 Hospital de San José de Bogotá - Department of Internal Medicine - Bogotá D.C. - Colombia.

14 Fundación Universitaria de Ciencias de la Salud - Department of Internal Medicine - Bogotá D.C. - Colombia.

15 Fundación Santa Fé de Bogotá - Neurocritical Care Unit - Bogotá D.C. - Colombia.

16 Hospital Universitario Nacional de Colombia - Assistant Directorate of Medical Clinics - Bogotá D.C. - Colombia.

17 Hospital Universitario Nacional de Colombia - Intensive Care Division - Bogotá D.C. - Colombia.

18 Hospital Universitario Nacional de Colombia - Auditing Department - Bogotá D.C. - Colombia.

19 Hospital Universitario Nacional de Colombia - Rehabilitation and Human Development Directorate - Bogotá D.C. - Colombia.

20 Universidad Nacional de Colombia - Bogotá Campus - Faculty of Sciences - Department of Pharmacy - Bogotá D.C. - Colombia.

21 Hospital Universitario Nacional de Colombia - Nursing Department - Bogotá D.C. - Colombia.

Open access

Received: 22/02/2021

Accepted: 11/11/2021

Corresponding author: Jorge Alberto Cortés. Departamento de Medicina Interna, Facultad de Medicina, Universidad Nacional de Colombia. Bogotá D.C. Colombia. Email: jacortesl@unal.edu.co.

Keywords: Clinical guidelines as Topic; Pneumonia; Respiratory tract infections; Community-Acquired Infections; Colombia (MeSH).

Palabras clave: Guías de Práctica Clínica como Asunto; Neumonía; Infecciones del sistema respiratorio; Infecciones comunitarias adquiridas; Colombia (DeCS).

How to cite: Cortés JA, Cuervo-Maldonado SI, Nocua-Báez LC, Valderrama MC, Sánchez EA, Saavedra A, et al. Clinical practice guideline for the management of community-acquired pneumonia. Rev. Fac. Med. 2022;70(2):e93814. English. doi: https://doi.org/10.15446/revfacmed.v70n2.93814.

Cómo citar: Cortés JA, Cuervo-Maldonado SI, Nocua-Báez LC, Valderrama MC, Sánchez EA, Saavedra A, et al. [Guía de práctica clínica para el manejo de la neumonía adquirida en la comunidad]. Rev. Fac. Med. 2022;70(2):e93814. English. doi: https://doi.org/10.15446/revfacmed.v70n2.93814.

Copyright: Copyright: ©2022 Universidad Nacional de Colombia. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, as long as the original author and source are credited.

Abstract

Pneumonia continues to be one of the main causes of consultation and hospitalization. Besides having a high impact in terms of morbidity and mortality, it is further aggravated by the current problem of antimicrobial resistance. Thus, establishing guidelines that allow adequate diagnosis and treatment is of great importance to obtain better clinical outcomes and promote a rational use of antibiotics in these patients. This clinical practice guideline (CPG) contains evidence-based recommendations for the diagnosis and treatment of community-acquired pneumonia in the adult population, which were developed by means of an evidence-based CPG adaptation process for the Colombian context.

Resumen

La neumonía sigue siendo una de las principales causas de consulta y de hospitalización a la que, además de su un alto impacto en términos de morbilidad y mortalidad, se suma la actual problemática de resistencia a los antimicrobianos, por lo que establecer directrices que permitan su adecuado diagnóstico y tratamiento es de gran importancia para obtener mejores desenlaces clínicos y promover un uso racional de antibióticos en estos pacientes. La presente guía de práctica clínica (GPC) contiene recomendaciones basadas en la evidencia para el diagnóstico y tratamiento de la neumonía adquirida en la comunidad en adultos, las cuales fueron realizadas mediante el proceso de adaptación de GPC basadas en la evidencia para el contexto colombiano.

Introduction

Pneumonia is an infection that can affect one or both lungs and presents with symptoms ranging from mild to severe, including cough (with or without mucus), fever, chills, and shortness of breath. The degree of severity of pneumonia depends on factors such as age, general health condition, and the origin of the infection.1 Although pneumonia can occur in people of all ages, the age groups most at risk for developing pneumonia and of it becoming severe are children aged 2 years and younger, and persons over 65 years of age.1 In fact, it has been reported that, compared to other age groups, the highest overall pneumonia mortality rate is reported in people aged 70 years or older, with 261 pneumonia deaths per 100 000 people in 2017 for this age group.2 Moreover, also in 2017, the overall mortality rate for pneumonia was 15 deaths per 100 000 people.2

In the United States, pneumonia was the most common primary diagnosis in hospitalized patients in 2014 (41.2% in intensive care unit [ICU] patients and 36.6% in inpatients), and respiratory diseases were the most common cause of death in patients with two or more prior emergency department visits (36.1%) and the second most common cause in those with one prior emergency department visit (25.9%).3 In Colombia, in 2010, the population aged 80 years or older was the age group with the highest annual consultation and hospitalization rates (873 consultations and 100 hospitalizations per 1 000 person-years, respectively), while lower respiratory tract infection was the disease with the second highest annual incidence rate (2 232 new cases per 100 000 persons).4

Besides its impact in terms of morbidity and mortality, and because the use of antimicrobials is one of the therapeutic options to be considered in pneumonia, its proper diagnosis and treatment has an impact on the development of antimicrobial resistance. Since 2014, this situation has been considered a public health problem by the World Health Organization (WHO),5 which included community-acquired microorganisms such as Streptococcus pneumoniae, one of the main etiological agents of community-acquired pneumonia (CAP), in the list of species of greatest concern for antimicrobial resistance.6 CAP is defined as acute parenchymal lung infection that is acquired in a community setting and is not associated with health care in a hospital, nursing home, or other health care setting.7

Therefore, establishing guidelines to direct the treatment of this group of patients is important in order to obtain better clinical outcomes and promote a rational use of antibiotics in this setting. In Colombia, the last national guideline for the management of CAP was published in 2013,8 so it is necessary to review and update the recommendations for the management of this infection in the country, without overlooking the specific recommendations for the care of COVID-19 patients,9 which, depending on the need or appearance of new evidence, may be reviewed and updated eventually.

Scope of the clinical practice guideline (CPG)

This CPG is intended for health care workers involved in the care of adult patients (>18 years of age) with a clinical suspicion or confirmed diagnosis of CAP and for decision makers or entities involved in the generation of health policies related to the management of this condition. This CPG includes recommendations for the diagnosis and treatment of CAP in the Colombian context.

Objective of the clinical practice guideline

To systematically generate evidence-based clinical recommendations for the diagnosis and treatment of adult patients with a clinical suspicion or confirmed diagnosis of CAP in order to optimize the quality of health care provided to these patients in the country and, thus, obtain better clinical outcomes and promote the appropriate and safe use of antimicrobials in the treatment of this population.

Population targeted by the CPG

The recommendations contained in this CPG address the following patient groups:

  • Adult patients (>18 years)
  • Patients with clinical suspicion or confirmed diagnosis of CAP.
  • Patients with clinical suspicion or confirmed diagnosis of aspiration pneumonia.

Population not targeted by the CPG

The recommendations contained in this CPG do not include the following population groups:

  • Pediatric population (<18 years of age).
  • Pregnant women
  • Patients with clinical suspicion or confirmed diagnosis of health care-associated pneumonia.
  • Patients with clinical suspicion or confirmed diagnosis of ventilator-associated pneumonia.
  • Patients with acute exacerbation of chronic obstructive pulmonary disease.
  • Patients with primary or secondary immunodeficiency.

Intended users of the CPG

The recommendations contained in this CPG are aimed at health workers involved in the health care process of adult patients with a clinical suspicion or confirmed diagnosis of CAP at the different levels of health care of the Colombian General Social Security Health System (I, II, III, and IV), namely, general practitioners; specialists in emergency medicine, family medicine, internal medicine, critical medicine and intensive care, pulmonology, and infectious diseases; nurse practitioners; clinical laboratory staff; pharmaceutical chemists; and other personnel involved in the diagnosis and treatment of patients with CAP.

Methodology

This CPG was developed in accordance with the standards established in the Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia (Methodological Guidelines for the Implementation-Adaptation of Evidence-Based Clinical Practice Guidelines) of the Ministry of Health and Social Protection of Colombia,10 as described below.

Composition of the guideline development group

The guideline development group (GDG) consisted of eight members distributed as follows: two specialists in adult infectious diseases (JAC, SIC), four specialists in adult pulmonology (EAS, AS, JVT, DPA), one specialist in internal medicine (LCN), and two clinical epidemiologists with experience in the development of CPGs, systematic literature reviews, synthesis and qualification of evidence, and participatory processes (JAC, MCV).

Prior to the start of the development of the GPC, each of the GDG members declared whether or not they had conflicts of interest by filling out a conflict-of-interest disclosure form designed for this purpose. When a conflict of interest was declared, an analysis was carried out to define its impact on the member’s participation in the different CPG development activities.

The scope and objectives of the CPG, as well as the aspects to be addressed, were defined during informal consensus meetings in which all members of the GDG participated.

GPC search

Once the scope and objectives of the CPG were established, a systematic search of CPGs was conducted to identify guidelines published in any language between 2015 and 2020 that addressed the issues set out in the scope of the present guideline.

The websites of the following CPG compilers and developers were consulted: Guidelines International Network, Agency for Healthcare Research and Quality/National Guidelines Clearinghouse, CMA Infobase: Clinical Practice Guidelines, Catálogo de Guías de Práctica Clínica en el Sistema Nacional de Salud (Guía Salud), National Institute for Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network, New Zealand Guidelines Group, and American College of Physicians.

Systematic searches were also performed in MedLine, LILACS and Epistemonikos using search strategies adapted for each search engine and utilizing Boolean, truncation and proximity operators, as well as free-text terms and controlled vocabulary, including key terms such as “community-acquired infections” and “respiratory tract infections”. The Medline search strategy is outlined in Supplementary Table 1.

Screening, quality assessment, and selection of CPGs to be used for the development of the guideline

Once the searches were performed, and after removing duplicates, two reviewers (MCV, LCN) independently performed the primary screening of the records retrieved by reading the title and abstract, selecting the documents classified as CPG or evidence-based recommendations that addressed at least one of the aspects defined in the scope of this guideline. Subsequently, two reviewers (MCV, LCN) independently performed the secondary screening (full-text reading) of the references selected in the previous step, using the modified 7 tool (i.e., Guideline Implementability Appraisal tool) proposed in the Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia of the Colombian Ministry of Health and Social Protection.10 Disagreements on the inclusion of a CPG were resolved by consensus or through the intervention of a third reviewer in cases where agreement between the two reviewers could not be reached.

Even though, as mentioned above, there were no publication language restrictions in the CPG searches, studies published in languages such as German, Japanese or Korean were excluded during the full-text reading screening stage and only those published in English or Spanish were taken into account, because the reviewers were not fluent in the former languages.

Next, the selected CPGs were presented to the development group in order to evaluate their methodological quality using the AGREE II tool.11 Each guideline was evaluated independently by three reviewers, and at least one clinical expert and one methodological expert always participated in the process. Furthermore, when there was doubt as to the information available for the evaluation of the CPG, additional information from the developer groups was requested by email.

After completing the quality assessment process, CPGs with a score ≥60% in the domains of methodological rigor and editorial independence were selected. Finally, in accordance with the recommendations of the Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia of the Colombian Ministry of Health and Social Protection,10 and with the aim of selecting the CPGs to be used in the adaptation process, the GDG analyzed the selected guidelines taking into account the following aspects: the topics addressed in the guidelines, the use of the GRADE methodology, the year of publication, and the date of the last search for evidence reported in the guideline.

Based on the methodology described above, two CPGs were selected for the adaptation process, namely, the American Thoracic Society and Infectious Diseases Society of America (ATS / IDSA) CPG: Diagnosis and Treatment of Adults with Community Acquired Pneumonia, an Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America,12 and the National Institute for Clinical Excellence (NICE) CPG: Pneumonia (community-acquired): antimicrobial prescribing [NG138],13 both published in 2019. To adapt the recommendations to the Colombian context, authorization was obtained from the authors of both CPGs (Metlay JP and NICE).

Adaptation of recommendations

The GDG carried out the adaptation process using the GRADE methodology, (specifically the GRADE EtD tool),14,15 based on the information provided in the two selected CPGs. The GRADE evidence profiles were also included along with the evaluation of the certainty of the evidence, which was completed by analyzing each of the following domains: number and design of studies, risk of bias, inconsistency, indirect evidence, imprecision, and other considerations. All this was done taking into account considerations specific to the Colombian context, the benefits and harms of the different options, the use of resources, the impact on equity, and the feasibility of implementation.

Expert consensus

The adapted recommendations were presented at three expert consensus meetings with the participation of representatives from different health sciences disciplines and scientific societies (“Asociación Colombiana de Infectología - ACIN [JP, FOG, IR], Asociación Colombiana de Neumología y Cirugía del Tórax - Asoneumocito [FM], Asociación Colombiana de Medicina Interna - ACMI, Asociación Colombiana de Medicina Crítica y Cuidado Intensivo - AMCI [JARC], professionals in the areas of microbiology, respiratory therapy, pharmacy, nursing and health auditing [ALL, IJG, SLC, JAD, NG, FG]), as well as patient representatives (Asociación de usuarios de Méderi [JEM, MP]), thus including the perspective of the various stakeholders.

At the consensus meeting, through a participatory process using Delphi methodology in real time and taking into account the information and evidence provided by the two selected CPGs and the considerations specific to the Colombian context suggested by the clinical experts, recommendations were formulated and graded according to the GRADE16 methodology, and good practice points were formulated, which allow good clinical practice in patient management.

Voting during consensus was conducted anonymously and electronically. Agreement was defined as reached if more than 50% of the voters were in favor or against a recommendation or good practice point. In cases in which no agreement was reached in the first round, a discussion session was held followed by a new voting round; a maximum of three voting rounds were allowed for each recommendation and/or good practice point.

Quality of evidence grades

  • High: We are very confident that the true effect is close to the estimate of effect.
  • Moderate: We are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it could be substantially different.
  • Low: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.
  • Very low: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.

Implications of strong and weak recommendations

Implications of a strong recommendation are:

  • For patients: Most individuals in this situation would want the recommended course of action and only a small number would not.
  • For clinicians: Most individuals should receive the recommended course of action.
  • For policy makers: The recommendation can be adapted as policy in most situations.

Implications of a weak (conditional) recommendation (suggestion) are:

  • For patients: The majority of individuals in this situation would want the suggested course of action, but many would not.
  • For clinicians: Recognize that different choices will be appropriate for different patients, and that you must help each patient arrive at a management decision consistent with her or his values and preferences.
  • For policy makers: Policy making will require substantial debates and involvement of many stakeholders.

Questions addressed in the guidelines

1.Should sputum Gram stain and culture be performed for diagnosing CAP in adults?

2.Should blood cultures be performed for diagnosing CAP in adults?

3.Should urinary antigen testing be performed for diagnosing CAP in adults?

4.Should influenza virus testing be used for diagnosing CAP in adults?

5.Should clinical prediction rules be used to determine the healthcare setting in which adult CAP patients should be treated?

6.Should the procalcitonin test be used to define the initiation of antimicrobial therapy in adults with CAP?

7.What is the best strategy for empirical antimicrobial therapy in adult outpatients with CAP?

8.What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP?

9.What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa?

10.What is the appropriate duration of antimicrobial therapy in adult patients with CAP, both outpatients and inpatients?

11.What is the appropriate route of administration of antimicrobial therapy in adult patients with moderate to severe CAP?

12.Should antiviral therapy be included in the treatment of adult patients with CAP who test positive for influenza?

13.Should corticosteroids be used in adult inpatients with CAP?

Recommendations and evidence review

Microbiological diagnosis

Question Nº 1. Should sputum Gram stain and culture be performed for diagnosing CAP in adults?

Recommendations

  • We do not recommend routine sputum Gram stain and culture in adult outpatients with CAP (strength of recommendation: strong against; quality of evidence: very low ⨁◯◯◯).
  • We recommend performing Gram stain and culture of lower respiratory tract secretions prior to initiating antimicrobial therapy in hospitalized adult patients with CAP who:
    • Have been diagnosed with severe CAP (Table 1) (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or
    • Are receiving empiric antimicrobial therapy for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or
    • Have a history of MRSA or P. aeruginosa infection, especially patients with previous respiratory tract infection with one of these pathogens (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯); or
    • Have a history of hospitalization and antimicrobial therapy in the last 90 days (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯).

Table 1. Criteria for severity of community-acquired pneumonia.

Minor criteria

  • Respiratory rate ≥30 respirations per minute.
  • PaO2 / FiO2 ratio ≤250
  • Multilobar infiltrates
  • Confusion / disorientation
  • Uremia (blood urea nitrogen level ≥20 mg/dL)
  • Leukopenia (white blood cell count <4 000 cells/mL)
  • Thrombocytopenia (platelet count <100 000 / mL)
  • Hypothermia (core temperature <36° C)
  • Hypotension requiring intensive fluid resuscitation

Major criteria

  • Septic shock with need for vasopressors
  • Respiratory failure requiring invasive mechanical ventilation

CAP is considered severe if the patient meets 1 major or 3 or more minor criteria.

Source: Adapted from Mandell et.al.17

Good clinical practice point

Respiratory tract specimen quality should be judged based on the Murray & Washington criteria,18 and the report should be interpreted only if the specimen result is category 2 or 3. See Table 2.

Table 2. Murray & Washington criteria.

Squamous epithelial cells per low-power field

0

1-9

10-24

More than 25

Neutrophils per field

0

3

0

0

0

1-9

3

0

0

0

20-24

3

1

0

0

More than 25

3

2

1

0

Source: Adapted from Murray & Washington.18

Rationale for the recommendation

Gram staining is an easy and quick test that can be performed in most health institutions, even in low complexity centers. Initially designed to identify S. pneumoniae, it allows to rapidly determine the microbial etiology of CAP. Conversely, sputum culture entails more difficulty due to the usual limitations for the growth of S. pneumoniae and a number of important causative microorganisms, especially intracellular bacteria.

In clinical practice, according to what has been reported in the literature, the results of sputum Gram stain or culture may have a very limited impact on decisions regarding the treatment of CAP in the outpatient setting. Given the low quality of evidence of the benefit of performing cultures of respiratory specimens from adult patients with CAP in the outpatient setting, the consensus group agreed to recommend against performing sputum Gram stain and culture in this context.

However, there are two cases in which sputum culture and Gram stain are recommended. The first is endotracheal aspirate culture in patients with severe CAP requiring intensive care with endotracheal intubation, since McCauley et al.19 found that, for intubated patients with CAP, tracheal aspirate culture was the only positive test in 39% of cases (32 of 89) when other diagnostic tests such as blood cultures and urinary antigen tests were negative. The second case in which we recommend performing sputum culture and Gram stain is patients with suspected MRSA or P. aeruginosa infection to confirm their etiology and/or adjust antibiotic treatment based on the results of these tests; although evidence on risk factors associated with the presence of these microorganisms is not solid, it has been reported that situations such as a history of infection by these bacteria and previous antibiotic treatment or hospitalization in the last 90 days may be associated with an increased risk of MRSA or P. aeruginosa.

In addition, sputum cultures on admission in referral hospitals may be helpful in decision-making regarding antimicrobial therapy in these patients, as well as in identifying those who have been admitted with previous airway colonization. This recommendation aims to promote the rational use of antimicrobials when treating these patients by enabling the adjustment of the antimicrobial scheme once the culture results are available.

Summary of evidence

The studies that were identified to establish these recommendations are observational and, in general, the quality of the evidence is very low. Firstly, the criteria for differentiating patients with severe CAP are set out in Table 1,17 while the Murray and Washington criteria for interpreting the sputum Gram stain are presented in Table 2.18 Signori et al,20 in a study involving 274 hospitalized patients with CAP, evaluated the frequency of sputum culture and its association with mortality, finding a mortality rate of 32.7% in patients who did not present with expectoration (n=58), 20.9% in patients with expectoration but from whom sputum samples were not collected for culture (n=124), and 6.5% in patients from whom sputum samples were collected for culture (n=124), with a higher risk of mortality in the group with expectoration but from whom sputum samples were not collected (OR: 3.78, 95%CI: 1.40-10.23). Moreover, in the study by Uematsu et al.,21 conducted in Japan with data from 65 141 adult hospitalized patients with CAP, no association was found between sputum testing and 30-day mortality (OR: 1.06, 95%CI: 0.98-1.15; p=0.013), nor with length of hospital stay (HR: 0.98, 95%CI: 0.97-1.00; p=0.071).

Studies on the usefulness of sputum Gram staining in the hospital setting, such as the one conducted in Japan by Sato et al.22 in 144 CAP cases requiring hospitalization, have shown no significant difference in length of hospital stay (9.67 days with the test vs. 11.75 days without the test, p=0.053) nor in time on intravenous antimicrobial therapy (6.73 days with sputum Gram staining vs. 7.91 days without the test, p=0.44). These findings have been confirmed in other studies on microbiological testing that have shown that establishing an etiologic diagnosis using sputum Gram stain or culture routinely in settings with a low frequency of resistant pathogens does not have a significant impact on mortality, length of hospital stay, changes in antimicrobial therapy, or the overall clinical prognosis of these patients.23,24

In Colombia, there is insufficient information to evaluate the economic impact of the implementation of these recommendations. In the existing literature, no local data on the costs of medical care for CAP were found. Although the consensus meeting took into account data on the costs of some supplies, medications, hospitalization, among other factors involved in the care of these patients in the country, it was not possible to make an actual assessment of the cost-effectiveness of these recommendations. There were also no studies that allowed us to evaluate, from any perspective, the effect of the recommendations on health equity in minority or disadvantaged populations. These two aspects were considered as issues to be investigated in Colombia in order to better establish potential recommendations in future versions of the guideline.

Question Nº 2. Should blood cultures be performed for diagnosing CAP in adults?

Recommendations

We do not recommend performing blood cultures in adult outpatients with CAP (strength of recommendation: strong against; quality of evidence: good: ⨁◯◯◯).

We recommend performing blood cultures prior to initiating antimicrobial therapy in hospitalized adult patients with CAP who:

  • Have been diagnosed with severe CAP (Table 1) (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or
  • Have risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or
  • Have a history of MRSA or P. aeruginosa infection, especially patients with a history of respiratory tract infection by one of these pathogens (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯); or
  • Have a history of hospitalization and antimicrobial therapy in the last 90 days (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯).

Good clinical practice point

The blood culture set should be collected according to the parameters defined in the manual of procedures for sample collection issued by the Instituto Nacional de Salud (National Health Institute or INS by its acronym in Spanish).25

Rationale for the recommendation

Blood cultures allow the identification of microorganisms in the blood at the time of CAP diagnosis. However, most patients will not present with bacteremia, which is limited to S. pneumoniae, S. aureus, and Enterobacteriaceae infections, and to patients with comorbidities or severe forms of the disease.

Evidence on the benefit of performing blood cultures in all CAP patients has a very low quality, so the recommendation is limited to certain groups of patients who could be considered at higher risk, such as those with severe CAP or with risk factors for microorganisms such as MRSA or P. aeruginosa. In addition, routine performance of this test may lead to false positives that promote indiscriminate use of antimicrobials in the context of CAP treatment. Another reason for not recommending the routine performance of blood cultures is that results may take more than 48 hours, so treatment adjustment may be delayed or no longer relevant in outpatients or inpatients with mild or moderate CAP.

Summary of evidence

The reviewed studies on the usefulness and benefit of taking blood cultures in CAP patients are observational. For instance, Meehan et al.,26 in a study evaluating which care strategies in hospitalized CAP patients were associated with mortality outcome in a sample of 14 069 older adults (≥65 years) hospitalized in different parts of the United States, found that the performance of blood cultures, both before initiating antibiotic administration and within the first 24 hours of administration, did not show a benefit with respect to 30-day mortality (adjusted OR: 0.92, 95%CI: 0.82-1.02; p=0.10 and adjusted OR: 0.90, 95%CI: 0.81-1.00; p=0.07).

Similarly, another study conducted in the United States in 1 062 adult inpatients with CAP reported that the performance of blood cultures within the first 24 hours after hospital admission or before the administration of antimicrobials had no impact on mortality (adjusted OR: 0.86, 95%CI: 0.36-2.07 and adjusted OR: 1.21, 95%CI: 0.62-2.34, respectively), nor on length of hospital stay (adjusted OR: 1.04; 95%CI: 0.72-1.50 and adjusted OR: 0.84, 95%CI: 0.60-1.17, respectively). However, there was an association between performing blood cultures during the first 24 hours after hospital admission and an increased risk of clinical instability at 48 hours (adjusted OR: 1.62, 95%CI: 1.13-2.33).27

Along these lines, Costantini et al.,28 in a study comparing two cohorts of CAP patients admitted to a hospital in Italy in 2005 (n=234) and 2012 (n=321), found that the performance of this test was not associated with a benefit for in-hospital mortality (OR: 0.67, 95%CI: 0.37-1.21), nor for 30-day mortality (OR: 0.6, 95%CI: 0.32-1.09). Finally, it has been described that, in the context of routine blood culture performance in patients with non-severe CAP, the rate of contaminated blood cultures is 3.1% and that, consequently, it is likely that there are many more false positives (e.g., growth of coagulase-negative staphylococci that colonize the skin of patients and are not related to CAP) than true positives, thus promoting the indiscriminate use of antibiotics in the treatment of these patients.29

Question No. 3. Should urinary antigen testing be performed for diagnosing CAP in adults?

Recommendations

  • We suggest performing pneumococcal urinary antigen testing in adults with severe CAP (Table 1) (strength of recommendation: weak for; quality of evidence: low ⨁⨁◯◯).

Rationale for the recommendation

Randomized clinical trials of urinary antigen testing for Legionella and S. pneumoniae have not shown a clear benefit in terms of clinical outcomes in patients with severe CAP requiring ICU management. On the other hand, observational studies unfortunately have a low quality, and their results are often contradictory: some suggest that urinary antigen testing for Legionella is associated with a decrease in mortality in hospitalized patients with CAP, while others conclude that there is no such benefit.

Furthermore, no studies evaluating only the role of urinary antigen testing in hospitalized patients with severe CAP were found; instead, the studies include other diagnostic laboratory tests and multiple care strategies, so it is unclear whether the results can be attributed to urinary antigen testing alone or to diagnostic and therapeutic strategies in general. Although Legionella infection carries a high burden in terms of mortality in the context of severe CAP, we consider that the benefit of performing urinary antigen testing to determine its presence is very limited considering that this microorganism would already be covered by the empirical antimicrobial treatment scheme implemented in CAP patients considered to be at high risk. Regarding the performance of pneumococcal urinary antigen testing, the consensus group agreed to recommend this practice in patients with severe CAP, since it has been reported that its use may be related to a decrease in mortality.28

Summary of evidence

Evidence on the use of urinary antigen testing for detecting microorganisms when diagnosing CAP is conflicting. For example, Costantini et al.28 found that taking these tests, including pneumococcal and Legionella urinary antigen tests, was associated with a decrease in in-hospital mortality and 30-day mortality (OR: 0.427, 95%CI: 0.215-0.850 and OR: 0.341, 95%CI: 0.170-0.685, respectively), a finding also reported by Uematsu et al.21 for 30-day mortality (OR: 0.75, 95%CI: 0.69-0.82; p<0.001).

On the other hand, Falgera et al.,30 in a study of 177 hospitalized CAP patients evaluating the impact of a treatment strategy based on the urinary antigen test result (n=88) compared to empirical treatment (n=89), showed, in a intention-to-treat comparative analysis, that the performance of this test did not have any benefit in terms of mortality, clinical relapse, ICU admission, days of hospital stay, need for readmission, adverse events, duration (in days) of antimicrobial treatment, and duration (in days) of intravenous treatment.

Question Nº 4. Should influenza virus testing be used for diagnosing CAP in adults?

Recommendations

We recommend testing for influenza viruses, preferably using rapid molecular assays for influenza viral RNA or nucleic acid detection, rather than the rapid influenza antigen detection test in patients:

  • Diagnosed with severe CAP (Table 1) (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁), or
  • Who have a comorbidity (respiratory, cardiovascular or immunosuppression) (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯).

Rationale for the recommendation

Evidence on the usefulness of testing for influenza viruses in patients with CAP is scarce; moreover, the reported results are controversial. Available information comes from studies conducted in patients with lower respiratory tract infection, in a group of individuals with CAP, and not in a population of patients infected only with influenza. Epidemiological studies have reported that the prognosis of patients with severe CAP or CAP and comorbidities worsens when they have an infection caused by one of the influenza viruses, so the consensus group decided to recommend molecular assays for influenza viral RNA or nucleic acid detection in these two clinical scenarios.

Summary of evidence

No studies evaluating the usefulness of testing for influenza viruses in patients with CAP were found. The few papers found involved individuals with lower respiratory tract infection, such as the randomized clinical trial conducted by Oosterheert et al.31 in 107 patients (51.4% with CAP) to evaluate the feasibility and clinical and economic impact of using the TaqMan PCR test for the detection of respiratory viruses and atypical pathogens, in which it was found that, compared to the control group (n=52; use of conventional diagnostic procedures) there was no change in 28-day mortality, duration of antimicrobial treatment, or length of hospital stay.

Treatment

Question Nº 5. Should clinical prediction rules be used to determine the healthcare setting in which adult CAP patients should be treated?

Recommendations

  • We recommend using clinical judgment along with a validated clinical prediction rule, either the pneumonia severity index (PSI) or the CURB-65 or CRB-65 pneumonia severity scores, to assess the severity of illness and determine the need for hospitalization in adults diagnosed with CAP (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯).

Good clinical practice point

  • Clinical judgment, along with the 2007 IDSA/ATS pneumonia severity criteria, should be used to determine the level of inpatient care in adults diagnosed with CAP who do not require vasopressors or mechanical ventilation.
  • Adults with CAP and hypotension requiring vasopressor therapy or with respiratory failure requiring mechanical ventilation should be admitted directly to the ICU.

Rationale for the recommendation

The use of clinical prediction rules to determine where patients with CAP should be treated (outpatient setting, general ward, or ICU) has been shown to be more effective and safer than clinical judgment, reducing variability in this decision among health care professionals. For patients with CAP classified for outpatient treatment and follow-up, a decrease in the cost of care and in the development of complications associated with inpatient treatment has been reported.

Even though the use of the severity and clinical prediction scores may vary because, depending on the level of care, laboratory and diagnostic tests required to calculate the values of these scores are not available in all health care centers, we recommend using one of these scores, with no preference in particular, to determine the health care setting in which these patients should be treated. In any case, besides the use of clinical prediction rules, the decision must be made taking into account clinical judgment, which includes the variability of the aspects considered in the prediction rules as well as sociodemographic, economic and support network factors of the patient.

Summary of evidence

Clinical prediction rules such as the PSI and CURB-65 pneumonia severity scoring system use demographic variables and clinical data obtained from laboratory and diagnostic tests to determine the prognosis of patients with CAP, especially 30-day mortality outcome.32-34 In this regard, Marrie et al.,35 in a multicenter controlled clinical trial conducted in 1 743 patients with CAP treated at the emergency department aimed to determine whether a critical care strategy that included clinical prediction rules had benefits in the treatment of these patients, found that using the PSI was a superior strategy in terms of classifying patients requiring outpatient treatment compared to not using any clinical prediction rules. They also found that the use of this score showed a benefit in terms of length of hospital stay, with a reduction in hospital readmission. These findings have been confirmed in other studies that have demonstrated that the use of the PSI in this population is safe, especially for selecting patients who only require outpatient care, and that this score has greater discriminating power to define the initial place of treatment for patients with CAP, without increasing the risk of mortality or morbidity.36,37

Studies on other clinical prediction rules for pneumonia are scant and results are less consistent. For example, in the case of the CURB-65 score, a randomized trial conducted in New Zealand comparing a group of patients with CAP who received inpatient treatment on a general ward (n=25) with a group who received outpatient treatment (n=24) had limitations in determining the differences between the two treatment strategies. One of them was related to the intravenous administration of antimicrobials under the supervision of nursing staff in the outpatient setting, which is a practice that is typical of the hospital setting and is referred to as “hospital-at-home” in several regions.38

The CURB-65 score includes simple variables that can be routinely recorded in the medical records, without the need for additional laboratory tests other than the blood urea nitrogen test, which facilitates its use in less complex health care settings and makes it an easier tool to use compared to other clinical prediction rules.39 In this regard, Aujeski et al.,40 in a study performed in 3 181 patients with CAP seen in the emergency departments of 32 hospitals of the United States and in which the performance of the PSI, CURB-65 and CURB clinical prediction rules for predicting 30-day mortality was evaluated, found that the diagnostic performance of the PSI was superior with an ROC curve of 0. 81 (95%CI: 0.78-0.84), showing a significant difference (p<0.01) in comparison with the other two scores (CURB: AUC=0.73, 95%CI: 0.68-0.76; CURB-65: AUC=0.76, 95%CI: 0.73-0.80).40

Question Nº 6. Should the procalcitonin test be used to define the initiation of antimicrobial therapy in adults with CAP?

Recommendations

  • We do not recommend performing procalcitonin (PCT) test in adults with clinically suspected CAP confirmed by imaging studies to decide, based on the test results, to initiate antimicrobial therapy (strength of recommendation: strong against; quality of evidence: moderate ⨁⨁⨁◯).

Rationale for the recommendation

Some of the studies that have described the use of the PCT test to determine the initiation of antimicrobial therapy in patients with CAP do not clearly meet the diagnostic criteria for pneumonia, and some do not even include the performance of an imaging study to confirm the diagnosis. For this reason, results about the benefit of performing this test in these patients may not be sufficiently reliable and conclusions may be controversial. For the GDG, the latter factor has the greatest weight for not recommending the PCT test to determine the initiation of antimicrobial therapy, since, in several clinical trials, patients with PCT values below the cut-off point for this serum marker and in whom antimicrobial treatment has not been initiated have favorable outcomes, while other patients with the same characteristics do not have a similar clinical course.

Other factors were considered that, based on the experience of the consensus group’s experts, do not support the use of this test in this context, including cost, the fact that it is not readily available at the various levels of health care, and the typical delay in reporting the results in some health care centers (up to 72 hours).

Summary of evidence

Several studies have attempted to establish a reliable cut-off point for the serum PCT level to differentiate a CAP of viral etiology from one of bacterial origin, but so far it has not been possible to establish a standard threshold, although it is clear that the higher the value, the more likely it is that the origin is bacterial.41 For instance, the study conducted in Switzerland by Christ-Crain et al.42 in 243 patients (35.40% with CAP) found that the adjusted relative risk (RR) of antibiotic exposure was 0.49 (95%CI: 0.44-0.55; p<0.0001) in the group in which the PCT test was used (n=124) compared to the standard group (clinical trial only); however, other clinical outcomes such as mortality, length of hospital stay or development of complications were not evaluated.42 Likewise, a randomized controlled clinical trial conducted in Switzerland in 302 patients diagnosed with CAP reported that the use of PCT levels reduced antibiotic exposure (RR: 0.52, 95%CI: 0.48-0.55; p<0.01), antibiotic prescriptions on admission (85 vs. 99%; p<0.01), and duration of antibiotic treatment (median: 5 vs. 12 days; p<0.01), but, again, no prognostic clinical outcomes were assessed, and neither the length of hospital stay nor the risk of clinical failure.43

Regarding the evaluation of the impact of using this biomarker in terms of adverse effects, Schuetz et al,44 in a randomized controlled clinical trial conducted in 1 359 patients with lower respiratory tract infection admitted to the emergency departments of 6 hospitals in Switzerland, 68.1% of whom had CAP, found that, considering the reduction in the duration of antibiotic treatment, patients in the PCT group (n=671) had a lower risk of adverse events associated with antibiotic use. However, concerning undesirable outcomes such as death, ICU admission, disease-specific complications, or recurrent infection requiring antibiotic use during the last 30 days, the use of a PCT algorithm was not superior to the use of treatment strategies based on clinical judgment.

Furthermore, the limitations for its implementation in Colombia should be taken into account, since the PCT test is not available in all health care centers and its use is widely limited because it is not included in the health benefits plan. Consequently, given the importance of initiating antimicrobial treatment in a timely manner, its use could entail a delay in the initiation of antibiotic administration in patients who require it.

Question Nº 7. What is the best strategy for empirical antimicrobial therapy in adult outpatients with CAP?

Recommendations

  • We recommend using amoxicillin or, in case of penicillin allergy, doxycycline or clarithomycin, in adult patients diagnosed with CAP treated in the outpatient setting and without risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯).

Good clinical practice point

Quinolones should be avoided in the treatment of CAP.

Rationale for the recommendation

For this recommendation, the consensus group considered studies conducted in patients with CAP treated in the outpatient setting. To establish the first-line antimicrobial treatment, the most frequent etiological microorganisms in this population were considered; the proposed antimicrobial treatment schemes do not include coverage of atypical bacteria because no harmful outcomes have been reported in patients with CAP treated with amoxicillin. Another aspect in favor of the use of amoxicillin in monotherapy is that there are a large number of studies on the safety of this antimicrobial.

In cases in whom amoxicillin is contraindicated, such as patients with a history of allergy to this antibiotic, the consensus group recommended the administration of doxycycline or clarithromycin. These antimicrobials were not considered as first-line treatment for two reasons: first, the additional adverse effects of macrolides related, in particular, to electrocardiographic changes, arrhythmias, and increased risk of sudden death, and second, to promote the rational use of antimicrobials in this clinical setting.45

Finally, the use of this group of drugs for the treatment of CAP should be avoided as a good practice point bearing in mind that quinolone antibiotics increase the risk of inducing antimicrobial resistance in Gram-positive cocci and enterobacteria; the fact that they are used as second-line treatment for tuberculosis, an endemic disease in Colombia; and the frequency and severity of adverse effects related to the administration of these antibiotics.46,47 Prescription of antimicrobials should be based on the antibiotic susceptibility profile of the microorganisms causing CAP in each health care center. See Table 348-52 and Table 4.

Table 3. Frequency of microorganisms causing CAP in Colombia.

Microorganism

n * 7648

n* 31149

n* 13850

n+ 4851

n++ 6652

%

%

%

%

%

Bacteria

Streptococcus pneumoniae

36

27.6

16

23.4

12.5

Staphylococcus aureus

2

2.6

2.17

6.4

2.1

Staphylococcus spp. coagulase-negative staphylococci

2.2

1.45

2.13

4.2

Haemophilus influenzae

10

2.2

1.45

2.13

4.2

Enterobacteriaceae

3.5

3.5

2.9

14.9

6.2

P. aeruginosa and Acinetobacter baumanii

1

4.26

4.2

Moraxella catarrhalis

0.3

Atypical bacteria

Mycoplasma pneumoniae

22

13.8

8.56

12.5

Legionella pneumophila

1.9

2.9

2.13

2.1

Coxiella burnetii

5.8

2.13

4.2

Chlamydophila pneumoniae

1.3

8.7

2.13

4.2

Virus

Influenza A and B viruses

10

1.9

10.6

16.7

Adenovirus

7.1

8.51

10.4

Respiratory syncytial virus

4.2

0.72

8.51

6.2

Parainfluenza viruses 1, 2, and 3

1.9

0.72

8.13

2.1

Mycobacteria

Mycobacterium tuberculosis

2.9

0.72

Others

Mixed etiology

22.8

8.7

19.7

20.8

Unknown etiology

31.5

34

55.8

48.5

33.3

n*: number of patients.

n+: number of adults aged 65 and over.

n++ number of adults with severe CAP.

Source: Own elaboration.

Table 4. Antimicrobials and recommended dosages for the treatment of adult patients with CAP.

Antimicrobial

Dose

Interval

Observation

Renal adjustment

Oral

Amoxicillin

500 mg-1g

8 hours

Yes

Doxycycline

100 mg

12 hours

Loading dose of 200 mg

No

Clarithromycin

500 mg

12 hours

Yes, below 30mL/min

Amoxicillin/clavulanate

875/125 mg1000/125mg

8 hours

Preferably for oral administration following ampicillin/sulbactam

Yes

Cefuroxime axetil

1000 mg

8 hours

Absorption close to 52%

Yes

Linezolid

600 mg

12 hours

No

Endovenous

Ampicillin/sulbactam

1.5-3 g

6 hours

Yes

Ceftriaxone

1-2 g

24 hours

No

Cefuroxime

750 mg

8 hours

Intravenous or oral use according to patient’s oral tolerance and setting of care. See oral dosage above

Yes

Vancomycin

15 mg/Kg

12 hours

Loading dose or continuous infusion and serum levels and renal function monitoring are recommended. Continuous infusion can be done

Yes.

Nephrotoxic

Linezolid

600 mg

12 hours

Medication not included in the health benefit plan. Oral linezolid is included

No

Piperacillin/tazobactam

4.5 g

6 hours

It can be administered as a continuous/prolonged infusion

Yes

Cefepime

2 g

8 hours

Can be administered in continuous/ prolonged infusion. Risk of toxicity in patients with renal failure

Yes

Source: Own elaboration.

Summary of evidence

Data on the superiority or non-inferiority of antimicrobials in patients with CAP receiving outpatient treatment are scarce, as documented by a Cochrane review conducted in 2014.53 For example, Maimon et al.,54 found no significant differences in terms of morbidity or mortality, despite the fact that some antimicrobials did not cover atypical bacteria, in a meta-analysis that included five studies comparing the usefulness of macrolides vs. fluoroquinolones in the outpatient treatment of CAP; three comparing macrolides vs. beta-lactams; three comparing fluoroquinolones vs. beta-lactams; and two comparing cephalosporins vs. beta-lactam beta-lactamase inhibitors.

Similarly, Bonvehi et al.,55 in a study conducted in Argentina in 327 outpatients with CAP comparing the use of clarithromycin (n=160) vs. amoxicillin+clavulanate (n=167), reported that there were no significant differences between groups in clinical and microbiological response rates, nor in the presence of adverse effects. On the other hand, studies that have evaluated the usefulness of amoxicillin in this clinical setting have reported that, compared to the use of other antimicrobials such as broad-spectrum quinolones, the use of high doses of this drug has not shown any significant difference in terms of clinical success and adverse effects.56,57

Information on the frequency of microorganisms causing pneumonia in Colombia is limited. In general, three groups of microorganisms have been described: classical bacterial agents with a high virulence potential, including S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus; intracellular microorganisms, usually grouped as atypical, which include Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella spp, and Coxiella burnetii; and viruses, most notably influenza viruses, respiratory syncytial virus, rhinoviruses, coronaviruses, adenoviruses and, recently, SARS CoV-2 in the adult population. Table 3 presents information on the relative frequency of the most frequent microorganisms reported by Colombian studies conducted in patients with CAP.

The frequency of Streptococcus pneumoniae isolates in Colombia, as well as the relative frequency of the different serotypes and their antimicrobial resistance, has varied after the introduction and extensive use of pneumococcal vaccines in the Expanded Program for Childhood Immunization. Although penicillin resistance decreased during the first few years after its inclusion, penicillin, ceftriaxone, and macrolide resistance rates in S. pneumoniae isolates have increased in recent years due to the selection of certain serotypes not covered by the vaccine.58

Furthermore, according to data from the National Public Health Surveillance System - SIVIGILA, since 2017 the proportion of isolates that are not sensitive to macrolides and penicillins or ceftriaxone in adults is greater than 25% and 10%, respectively.59 This suggests that epidemiological surveillance for this microorganism should be maintained in the country, although the impact of its resistance to antimicrobials is still unclear in the context of pneumonia,60 and more studies are needed in this regard.

Question Nº 8. What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP?

Recommendations

Patients with moderate CAP:

  • We recommend using the following antimicrobial therapy in hospitalized adult patients with a diagnosis of moderate CAP and no risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):
    • Monotherapy with a beta-lactam (ampicillin/sulbactam) and re-evaluation 48 to 72 hours after treatment initiation to consider the need to add a macrolide (clarithromycin), taking into account aspects such as worsening of vital signs, ability to eat, and mental status.

In case the patient is allergic to penicillin, it is recommended to use (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):

  • Monotherapy with ceftriaxone; or
  • Monotherapy with cefuroxime; or
  • Monotherapy with doxycycline.

Patients with severe CAP:

  • We recommend using the following antimicrobial therapy in hospitalized adult patients with a diagnosis of severe CAP (Table 1) and no risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):
    • Combination therapy with a beta-lactam (ampicillin/sulbactam) and clarithromycin.
  • If the patient is allergic to penicillin, we recommend using (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):
    • Combination therapy with ceftriaxone (instead of ampicillin/sulbactam) and clarithromycin.

Good clinical practice point

  • Quinolones should be avoided in the treatment of CAP.
  • Anaerobic coverage should not be added to the treatment scheme for suspected aspiration pneumonia unless lung abscess or empyema are suspected.

Rationale for the recommendation

Recommendations for the treatment of CAP patients in the hospital setting are based on the treatment of the microorganisms that most frequently cause infection. There is no strong evidence on the benefits of using macrolides or antibiotics for the treatment of atypical bacteria in hospitalized patients with moderate CAP; studies comparing monotherapy with beta-lactam vs. beta-lactam with macrolide have not reported significant differences in that scenario. In the case of severe CAP, we recommend using a macrolide considering the coverage of atypical bacteria with high mortality burden such as Legionella and the additional effects of this group of drugs, such as modulation of inflammation. Furthermore, taking into account the quinolone resistance profile of the microorganisms that cause CAP and the adverse effects of these antibiotics, the use of this group of drugs for the treatment of these patients should be avoided as a good practice point. Antimicrobial prescription should be based on the antibiotic susceptibility profile of the microorganisms causing CAP in each health care center. See Tables 3 and 4.

Summary of evidence

Some studies have compared the use of beta-lactams with macrolides vs. monotherapy, although the latter with quinolones, and have reported that there are no differences between the two schemes; however, these studies have a low quality, small samples, and a non-inferiority design.61-63 Other research has evaluated the non-inferiority of beta-lactam and macrolide combination therapy vs. beta-lactam monotherapy, such as the open-label randomized clinical trial conducted by Garin et al.64 in 580 patients with CAP hospitalized in 6 hospitals in Switzerland, which did not report a clear difference between arms (monotherapy arm, n=291 vs. combination therapy arm, n=289), but did suggest that patients with intracellular microorganisms took longer to achieve clinical stability.64

Nevertheless, the results reported by Garín et al.64 differ from those described by Postma et al.65 who compared various treatment strategies for CAP (beta-lactam monotherapy vs. fluroquinolone monotherapy vs. beta-lactam and macrolide combination therapy) in a cluster-randomized crossover clinical trial in 2 283 patients with mild to moderate CAP requiring hospitalization. The authors concluded that beta-lactam monotherapy was not inferior to the other antimicrobial treatment options for the outcomes of 90-day mortality and length of hospital stay, the latter being similar for all strategies.

These data, taken together, suggest that the benefit of using combination therapy in hospitalized patients with mild or moderate CAP is unclear, as its use does not offer any benefits in terms of reduced risk of progression to more severe forms of the disease and reduced length of hospital stay, but instead may contribute to increased antibiotics use, higher resource expenditure, and increased risk of adverse effects. As an alternative for the treatment of patients who are allergic to penicillin, the consensus group recommended the use of ceftriaxone, a therapy included in the non-inferiority studies of beta-lactam monotherapy referred to above. Likewise, as indicated in the systematic reviews and meta-analysis of Picard et al,66 several clinical studies have evidenced the low frequency of cross-reactivity in allergic reactions in patients with a history of penicillin allergy who receive this drug. The next alternative in patients with a history of beta-lactam allergy is doxycycline, an antibiotic that has proven to be efficient due to its broad coverage of the causative microorganisms, as well as safe and cost-effective for the treatment of patients with mild to moderate CAP in the hospital setting.67

In patients with severe CAP, we recommend using beta-lactam plus macrolide to cover atypical bacteria such as Legionella, whose presence has been associated with a higher mortality rate, especially in older adults. In this regard, Nie et al,68 in a meta-analysis that included 16 cohort studies (42 942 patients with CAP), reported a significant decrease in mortality in patients who received combination therapy (beta-lactam+macrolide) compared to those who received monotherapy (beta-lactam) (adjusted OR: 0.67, 95%CI: 0.61-0.73; p<0.01).

A similar finding was also described in the systematic review and meta-analysis (14 studies; 33 618 patients) by Horita et al.,69 specifically in patients with severe CAP, where the random-model meta-analysis yielded an OR for all-cause mortality for beta-lactam plus macrolide compared with beta-lactam monotherapy of 0.80 (95%CI: 0.69-0.92; p<0.01). Collectively, this evidence suggests the benefit of using combination therapy in patients with severe CAP, which is related either to antibiotic coverage of Legionella species that may be associated with increased mortality, or to the effect of combination therapy in patients with severe CAP caused by S. pneumoniae.68

Question Nº 9. What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP and with risk factors for MRSA or P. aeruginosa?

Recommendations

  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of moderate or severe CAP and previous respiratory isolate of MRSA (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):
    • Initiate antimicrobial therapy based on the microbiological report of the previous respiratory isolate AND
    • Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results OR
    • Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results AND initiate antimicrobial therapy with vancomycin or linezolid.
  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of moderate or severe CAP and previous respiratory isolate of P. aeruginosa (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):
    • Initiate antimicrobial therapy based on microbiological report of previous respiratory isolate AND
    • Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm need for continued therapy based on results OR
    • Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on the results AND initiate antimicrobial therapy with piperacillin/tazobactam or cefepime.
  • We suggest taking the following actions in hospitalized adult patients with a diagnosis of moderate CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for MRSA or P. aeruginosa (strength of recommendation: weak for; quality of evidence: low ⨁⨁◯◯):
    • Perform culture or PCR of upper respiratory tract specimen AND
    • Initiate antibiotic treatment covering MRSA or P. aeruginosa only if results are positive.
  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of severe CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for MRSA (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):
    • Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results AND initiate antimicrobial therapy with vancomycin or linezolid, along with measurement of vancomycin levels, if appropriate.
  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of severe CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for P. aeruginosa (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):
    • Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results AND initiate antimicrobial therapy with piperacillin/tazobactam or cefepime.

Rationale for the recommendation

There are no clinical studies on predictors of MRSA or P. aeruginosa infection and there are no predictive scores to determine their presence. This, added to the fact that the prevalence of these microorganisms varies widely in each region and health care center in the country, led the consensus group to recommend the use of antimicrobials that cover MRSA or P. aeruginosa in patients with moderate to severe CAP and with a history of isolate of these microorganisms, as well as to perform culture or PCR of upper respiratory tract samples in order to establish a targeted treatment that promotes the rational use of antimicrobials.

The other clinical setting where we recommend antibiotic treatment of these bacteria is in patients with severe CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for the presence of MRSA or P. aeruginosa. The strength of this recommendation is weak, and the evidence has a low quality because no studies were found to support the increased risk of MRSA or P. aeruginosa infection in the presence of these factors; however, due to the high mortality of patients with severe CAP, the use of antibiotics covering these bacteria should be considered in this clinical setting.

Summary of evidence

The main risk factor for suspecting infection by P. aeruginosa or MRSA is a history of infection or colonization by one of these microorganisms; in this regard, for example, an OR of 6.21 (95%CI: 3.25-11.85) has been described for MRSA.70 Other risk factors include the presence of respiratory comorbidities (OR: 5.8, 95%CI: 2.2-15.3; p<0.01), having a history of hospitalization (OR: 3.8, 95%CI: 1.8-8.3; p=0.02),71 especially in the last 90 days, and the use of antimicrobials in the last 90 days (OR: 2.90, 95%CI: 1.13-7.45; p=0.02).72 An additional risk factor that should be considered to initiate antibiotic coverage is the epidemiology of these infections in the health care center, which should include the local antimicrobial susceptibility profile.

In patients with moderate or severe CAP and in whom, depending on the presence of risk factors, MRSA or P. aeruginosa infection is suspected, cultures or PCR of respiratory samples should be performed to confirm this etiology and adjust antimicrobial treatment. This is explained by the fact that antimicrobial stewardship is relevant, as it has been shown to be safe and to reduce the duration of antibiotic treatment, the length of hospital stay, and the frequency of complications related to adverse effects of broad-spectrum antimicrobials.73

In this regard, Cremers et al.74 found that, compared to no adjustment, adjusting antimicrobial therapy reduced mortality in patients with bacteremic nemococcal CAP (adjusted OR: 0.35, 95%CI: 0.12-0.99). Furthermore, Carugati et al.,75 in a study conducted with data from 261 hospitalized patients with CAP bacteremia, reported that adjustment of antimicrobial therapy (de-escalation) based on microbiological test results did not increase the risk of clinical failure in comparison with patients in whom antimicrobial therapy was de-escalated (RR: 0.89, 95%CI: 0.63-1.27; p=0.54). Nevertheless, in a recent large cohort study (88 605 hospitalizations due to CAP in the Veterans Affairs health care system medical centers), inverse propensity score–weighted regression of the weights showed that empirical use of linezolid or vancomycin in these patients did not decrease mortality but, on the contrary, increased it. 76

The costs of generic antimicrobials in Colombia are quite low and it is possible that the recommended therapeutic schemes are not expensive, both for intravenous and oral therapy. However, as mentioned above, formal evaluations of the cost-effectiveness of recommended treatments are needed in the region.

Question Nº 10. What is the appropriate duration of antimicrobial therapy in adult patients with CAP, both outpatients and inpatients?

Recommendations

  • Patients with mild to moderate CAP:

We recommend that the duration of antimicrobial therapy should not exceed 5 days in total and considering the following criteria for discontinuation: clinical stability of the patient (resolution of alterations in vital signs [heart rate, respiratory rate, blood pressure, oxygen saturation, and body temperature]), adequate tolerance to oral administration of food and fluids, and no alteration in mental status (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁).

  • Patients with severe CAP:

We recommend establishing the duration of antimicrobial therapy depending on the patient’s clinical course, microbiological test results, and biomarker levels (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯).

Good clinical practice point

If available, serum PCT testing may be used to determine whether to discontinue antimicrobial therapy in hospitalized patients.

Rationale for the recommendation

Taking into account that, in general, adequate antimicrobial prescription leads to clinical stability of patients 48-72 hours after starting treatment, we recommend a maximum duration of antimicrobial therapy of 5 days in patients with mild to moderate CAP and that discontinuation be decided based on clinical judgment, which includes criteria such as the absence of alterations in vital signs, adequate tolerance to oral administration of food and fluids, state of consciousness, and absence of complications. In cases of severe CAP, the duration of antimicrobial therapy should be established based on medical judgment, taking into account clinical and microbiological factors and monitoring of biomarkers such as serum PCT, if possible.

Summary of evidence

Historically, studies on the duration of antimicrobial treatment in patients with CAP have been grouped into two classes: a duration <7 days and a duration ≥7 days. The studies identified, such as that performed by el Moussaoui et al.77 in 119 patients with CAP, compare the use of amoxicillin, initially intravenously for 3 days and then orally for 5 more days, with the use of placebo in patients with mild to moderate CAP, concluding that although both strategies showed similar results in the outcomes of resolution of symptoms and changes in x-ray findings, the frequency of adverse effects was greater in the group of patients in which antibiotics were administered for 7 or more days (21% vs. 11%).

These results have been confirmed by other studies such as the one conducted by Dunbar et al.78 in 528 patients with mild to moderate CAP in which there was no statistically significant difference in clinical response rates or microbiological eradication rates between the use of levofloxacin for 5 days vs. the use of this drug for 10 days. Likewise, besides not finding discordant results between the duration of antibiotic treatment (7 days vs. 10 days) in hospitalized patients with severe CAP in terms of late recurrences or cure rates, Siegel et al.79 reported a shorter length of hospital stay, a lower frequency of adverse effects, and lower costs in the group of patients who received antibiotic treatment with a shorter duration.

It should be noted that the use of scores to evaluate the possibility of implementing antimicrobial treatments of even 3 days has also been suggested, since these scores, some of which have been translated into and culturally adapted to Spanish,80 take into account the symptoms and the subjective clinical evolution of the patient to define the time of treatment.

Discontinuation of antimicrobial therapy should be based on the clinical stability of the patient, understood as the presence of normal vital signs, adequate tolerance to oral administration of food and fluids, and the absence of altered mental status; in this sense, these findings are expected to be observed in patients with mild to moderate CAP 2 to 3 days after initiation of antimicrobial therapy.81,82 Furthermore, the assessment of patients’ clinical condition has been shown to reduce the length of hospitalization and duration of antimicrobial therapy, with no adverse impact on patient safety.83

Finally, it should be pointed out that there is currently no evaluation of the cost-effectiveness of the proposed interventions, although it is expected that they will be cost-effective, considering that they have the potential to reduce the length of hospital stay and, therefore, the possible associated complications, which would imply a reduction in the costs associated with the care of these patients since their use would allow early hospital discharge.

Question Nº 11. What is the appropriate route of administration of antimicrobial therapy in adult patients with moderate to severe CAP?

Recommendations

  • We recommend using oral antimicrobials as first-line treatment in adult patients with moderate to severe CAP, always taking into account tolerance to oral administration of food/drugs/fluids and severity of infection (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯).
  • We recommend reassessing the patient’s clinical condition 48 hours after starting intravenous antimicrobial therapy to consider switching to oral antimicrobials (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯).

Rationale for the recommendation

Initially, the route of administration of antimicrobials in patients with moderate to severe CAP was exclusively intravenous for the entire course of treatment. However, more recent studies have promoted the use of oral antimicrobials considering the decrease of adverse effects, the convenience of this route of administration, and the effectiveness of oral antimicrobial treatment, particularly in cases where 48 hours of intravenous therapy have already been completed and the patient is clinically stable. Therefore, the consensus group accepted and included this recommendation, as it encourages the rational use of antimicrobials, reduces the costs of care and hospital stay and, according to the evidence found, is a safe decision.

Summary of evidence

The evidence identified regarding the route of administration of antimicrobials in patients with moderate to severe CAP has a very low quality. For example, in a literature review, Cassiere & Fein84 report that switching from intravenous to oral administration in low-risk patients was an effective and safe intervention in the treatment of CAP. Likewise, Marras et al.,85 in a meta-analysis that included 7 studies (a total of 1 366 hospitalized adult patients with CAP), concluded that in patients with non-severe CAP who received oral antibiotic treatment, the strategy was effective and therapy lasted 1.3 days less (95%CI: 0.4%-2.2% days; p<0.01) than in the group of patients who received intravenous therapy.

Furthermore, based on the evidence found, the main costs of treating moderate to severe CAP are related to the duration of intravenous antimicrobial therapy and the length of hospital stay, so switching to oral antibiotics significantly reduces the costs of care for these patients, without this change implying harm to the patient or being associated with recurrences of infection and the development of complications.86 Once the patient is clinically stable and the switch from intravenous to oral antibiotics has been made, in-hospital observation is not required, so discharge, if there are no other contraindications, can be immediate, as confirmed by Nathan et al.87 in their retrospective study carried out with data obtained from the US Medicare National Pneumonia Project. In Colombia, the antimicrobials mentioned in the recommendations are covered by the health benefits plan of the Colombian health system.

Question Nº 12. Should antiviral therapy be included in the treatment of adult patients with CAP who test positive for influenza?

Recommendations

  • We recommend initiating influenza treatment (e.g., oseltamivir) in adult patients with severe CAP who test positive for influenza, regardless of the duration of illness prior to diagnosis (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯).

Rationale for the recommendation

Evidence on the use of influenza antiviral therapy in the context of CAP is very scarce and has a very low quality. No clinical trial that directly evaluated the usefulness of this type of treatment exclusively in patients diagnosed with CAP was found, but instead evidence comes from observational studies conducted in patients with different types of lower respiratory tract infections describing benefits in reducing the frequency of complications, the duration of symptoms, and the risk of mortality, even when antiviral administration is initiated more than 48 hours after the onset of symptoms. However, these results have not been consistent and have only been reported for patients with severe CAP. Moreover, the benefits of using these drugs have only been described in patients with a positive microbiological test for influenza virus, so the consensus group decided to make this recommendation only in this setting.

Summary of evidence

No clinical trials evaluating the use of oseltamivir in patients with CAP were found; in fact, very few studies were identified, and they have a very low quality with a high risk of bias. For example, Lee et al.88 reported that for hospitalized patients with confirmed influenza A/B respiratory infection (n=754), the use of antiviral drugs was significantly associated with a reduced risk of mortality (adjusted HR: 0.27, 95%CI: 0.13-0.55; p<0.01) and that early treatment (within 2 days after symptom onset) was associated with faster discontinuation of oxygen therapy (adjusted HR: 1.30, 95%CI: 1.01-1.69; p=0.04) and sooner hospital discharge (adjusted HR: 1.28, 95%CI: 1.04-1.57; p=0.01). McGeer et al.,89 in a study conducted in Toronto involving 512 hospitalized patients with a laboratory-confirmed diagnosis of influenza (185 children, none of whom died), reported that treatment with influenza antiviral drugs was associated with a significant decrease in mortality (OR: 0.21, 95%CI: 0.06-0.80) but that no benefit was observed for other outcomes such as length of hospital stay.

According to some of the initial clinical studies on this subject, such as the one conducted in the United States by Siston et al.90 with data from 788 pregnant women diagnosed with AH1N1 influenza, antiviral therapy should be initiated within 48 hours of symptom onset.90 However, good results have also been reported when this therapy is started 4 to 5 days after symptom onset.91

Although the usefulness of antiviral therapy has been reported primarily in the in-hospital setting, a reduction in the risk of complications has also been demonstrated in the outpatient setting. This was evidenced in a systematic review and meta-analysis that included 9 clinical trials (4 328 patients) where it was reported that the frequency of lower respiratory tract complications requiring antibiotics at 48 hours was lower in the group that received oseltamivir compared to the placebo group (4.2% vs. 8.7%), estimating a 44% reduction in the risk of these complications with treatment with this antiviral (RR: 0.56, 95%CI:0.42-0.75; p=00001), with an absolute risk difference of -3.8% (95%CI: -5.0 to -2.2).92 Concerning the in-hospital setting, Muthuri et al.,93 in a systematic review including individual data from 29 234 patients infected with H1N1pdm09 influenza virus and hospitalized during the 2009 pandemic, found that, compared with using no antiviral therapy, treatment with neuraminidase inhibitors (regardless of the time of onset) was associated with a reduction in the risk of mortality (adjusted OR: 0.81, 95%CI: 0.70-0.93; p=0.0024). Also, compared to late onset, early initiation of treatment (within the first 2 days after symptom onset) was also significantly associated with a reduction in the risk of mortality (adjusted OR: 0.50, 95%CI: 0.37-0.6; p<0.0001).

The use of oseltamivir and zanamivir (another neuroaminidase inhibitor) for the treatment of influenza has been extensively studied in the outpatient setting; in this regard, it has been reported that although these antiviral drugs mildly reduce symptoms, their use does not have a relevant clinical impact and their effect on reducing the use of antibiotics is low or null.94 Furthermore, a systematic review that included randomized controlled clinical trials conducted in patients with confirmed or suspected exposure to influenza virus reported that, although the use of oseltamivir reduced the time to first symptom relief in adults by 16.8 hours (95%CI: 8.4-25.1 hours; p<0.001), this drug was associated with an increase in the frequency of nausea, vomiting and psychiatric symptoms,95 thus concluding that its use in the outpatient setting is not very beneficial for these patients. In view of the above, the need to use this drug only in patients with a microbiologically confirmed diagnosis of influenza is strongly emphasized.

In Colombia, during the 2009 H1N1 influenza pandemic, the use of oseltamivir was implemented for the treatment of patients with severe acute respiratory infection, so the access to this drug is guaranteed since then in all health centers of the country. This fact makes this recommendation feasible with a limited impact on the costs currently incurred by healthcare centers associated with the care of these patients.96

Question Nº 13. Should corticosteroids be used in adult inpatients with CAP?

Recommendations

  • Patients with mild to moderate CAP:

We do not recommend using corticosteroids to treat patients with mild to moderate CAP (strength of recommendation: strong against; quality of evidence: moderate ⨁⨁⨁).

  • Patients with severe CAP (Table 1):

We suggest using corticosteroids in patients with severe CAP (strength of recommendation: weak for; quality of evidence: moderate ⨁⨁⨁◯).

Good clinical practice point

  • Provided there are no contraindications, use corticosteroids in patients with COVID-19.
  • Avoid the use of corticosteroids in patients with influenza.

Rationale for the recommendation

No studies were found to support the use of corticosteroids in patients with mild to moderate CAP; however, there is scientific evidence of the benefit of their use in patients with severe CAP in terms of mortality, requirement of mechanical ventilation, and length of stay in the ICU. Therefore, we suggest using these drugs in these patients taking into account clinical judgment, the absence of contraindications, and the analysis of the balance between risks and benefits, since their use is frequently associated with adverse effects, hyperglycemia being the most common, which could affect the clinical outcome of patients with sepsis of pulmonary origin. Corticosteroids and suggested doses to be used in these patients are presented in Table 5.97,98

Table 5. Corticosteroids for clinical use suggested to treat patients with severe CAP.

Glucocorticoids

Approximate equivalent dose (mg)

Relative glucocorticoid activity

Relative mineralocorticoid activity

Duration of action (hours)

Short-acting

Hydrocortisone

20

1

1

8-12

Cortisone

25

0.8

0.8

8-12

Intermediate-acting

Prednisone

5

4

0.8

12-36

Prednisolone

5

4

0.8

12-36

Methylprednisolone

4

5

0.5

12-36

Triamcinolone

4

5

0

12-36

Long-acting

Dexamethasone

0.75

30

0

36-76

Betamethasone

0.6

30

0

36-76

Mineralocorticoids

Fludrocortisone

0

15

150

24-36

Source: Adapted from Samuel et.al.97 and Liu et al.98

Summary of evidence

Some studies have documented the benefit of using corticosteroids in patients with severe CAP. Confalioniere et al.,99 in a multicenter randomized controlled trial conducted in 46 patients with CAP admitted to the ICU and receiving antibiotic treatment, found that, compared to placebo, the use of hydrocortisone infusion was associated with a significant decrease in hospital stay and mortality. However, it has not been possible to reproduce this considerable reduction in the risk of death of these patients in other studies and even some studies, such as the multicenter, randomized, double-blind, controlled trial conducted by Torres et al.100 in 120 patients with severe CAP, have described that the use of corticosteroids did not lead to a decrease in hospital stay or mortality.

At first, different meta-analyses, such as the one conducted in 2015 by Chen et al.101 (7 randomized clinical trials; 944 patients with CAP), documented that the use of these drugs (specifically glucocorticoids) was associated with a decrease in hospital stay, but more recent meta-analyses, such as the one conducted by Jian et al.102 (10 randomized clinical trials; 665 patients), have identified a significant reduction in mortality. In addition, other studies, such as the multicenter double-blind randomized controlled trial conducted by Blum et al.103 in 785 hospitalized adult CAP patients, have documented that the time to reach clinical stability is shorter in patients receiving steroids such as prednisone and that the use of these drugs is also associated with a reduction in the time requiring mechanical ventilation.

The use of steroids has been associated with important adverse effects such as alterations in glucose metabolism (hyperglycemia) and gastrointestinal bleeding. However, the clinical studies reviewed, at the doses and times recommended in this CPG, did not report an increase in the frequency of these events.102 Nevertheless, in the case of patients with pulmonary sepsis, the presence of adverse effects should be routinely evaluated, and appropriate measures should be taken for their prevention and timely control.

On the other hand, the use of steroids is a standard practice for the treatment of patients with COVID-19, so, provided there is no contraindication, these drugs should be used in these patients.9

Finally, according to a recently published meta-analysis that included 21 observational studies, corticosteroid use was associated with increased mortality in patients with influenza (OR: 3.9, 95%CI: 2.3-6.6, 15 studies; adjusted HR: 1.49, 95%CI: 1.09-2.02, 6 studies).104

Implementation and update of the CPG

This CPG should be implemented in health centers that provide health care services to adult patients with CAP in order to support activities related to the treatment of this population and programs to optimize the use of antimicrobial agents. Similarly, the indicators presented in Table 6 should be considered to measure the progress of the guideline’s implementation, with the frequency and reporting requirements that each institution deems pertinent.

Table 6. Indicators for measuring the implementation of the clinical practice guideline.

Indicator

Numerator

Denominator

Interpretation

Proportion of patients with sputum Gram stain and culture

Number of patients with severe CAP in whom sputum Gram stain and culture were performed

Total number of patients with severe CAP

This indicator identifies the use of sputum Gram stain and culture in patients with severe CAP

Proportion of patients with blood cultures

Number of patients with severe CAP in whom blood culture was performed

Total number of patients with severe CAP

This indicator identifies the use of blood culture in patients with severe CAP

Proportion of patients with influenza testing

Number of patients with severe CAP or comorbidity in whom influenza testing was performed

Number of patients with severe CAP or comorbidity

This indicator identifies the use of testing for influenza viruses in high-risk patients with CAP

Use of clinical prediction rules

Number of CAP patients requiring in-hospital care in whom a clinical prediction rule was used on admission

Total number of CAP patients admitted to hospital

This indicator identifies the use of clinical prediction rules in CAP patients admitted to hospital

Outpatient antimicrobial therapy

Number of CAP patients with outpatient management with an indication for treatment with amoxicillin

Total number of CAP patients treated on an outpatient basis

This indicator identifies the appropriate use of antibiotics in CAP patients under outpatient treatment

Inpatient monotherapy

Number of patients with mild or moderate CAP hospitalized in general ward receiving ampicillin/sulbactam monotherapy as initial treatment

Total number of patients with mild or moderate CAP hospitalized in the general ward

This indicator identifies the appropriate use of antibiotics in hospitalized patients with mild or moderate CAP

Inpatient combination therapy

Number of patients with severe CAP receiving combination therapy

Total number of patients with severe CAP admitted to the ICU

This indicator evaluates the appropriate use of antibiotics in patients with severe CAP admitted to the ICU

Duration of outpatient therapy

Number of patients with mild CAP treated on an outpatient basis and with indication for antibiotic treatment for 5 days or less

Total number of CAP patients under outpatient treatment

This indicator identifies the appropriate duration of antibiotic therapy in CAP patients requiring only outpatient treatment

Duration of inpatient therapy

Number of hospitalized patients with mild or moderate CAP who receive antibiotic treatment for 5 days or less

Total number of patients with mild or moderate CAP hospitalized in the general ward

This indicator identifies the appropriate duration of antibiotic treatment in patients with mild or moderate CAP hospitalized in the general ward

Oral antimicrobial therapy

Number of patients with mild or moderate CAP hospitalized in general ward receiving oral antibiotic treatment as initial strategy

Total number of patients with mild or moderate CAP hospitalized in the general ward who tolerate oral administration of antibiotics

This indicator identifies the frequency of use of oral antibiotic therapy in patients with mild or moderate CAP hospitalized in the general ward

Switching from intravenous to oral antibiotics

Number of CAP patients hospitalized in the general ward and who were switched to oral antibiotic therapy following reevaluation 48 hours after the start of intravenous antimicrobial therapy

Total number of CAP patients hospitalized in the general ward who initially received intravenous antibiotic therapy and tolerate oral administration of antibiotics

This indicator identifies the frequency of timely switching from intravenous to oral antibiotic therapy in CAP patients hospitalized in the general ward

Use of antiviral drugs

Number of patients with positive influenza test in whom oseltamivir treatment is initiated

Total number of CAP patients testing positive for influenza

This indicator identifies the use of antiviral drugs in patients with severe CAP

Use of steroids

Number of patients with severe CAP in whom steroid treatment is initiated

Total number of patients with severe CAP

This indicator identifies steroid use in patients with severe CAP

Source: Own elaboration.

In order to facilitate the implementation of this CPG, the following dissemination tools will be used to provide the country’s health professionals with better access to its contents: publication of the guideline in the Revista de la Facultad de Medicina of the Universidad Nacional de Colombia and on the website of the Asociación Colombiana de Infectología, as well as inclusion of the guideline recommendations in the contents of a massive open online course (MOOC) and a mobile application for CAP management.

Finally, it is considered that this CPG should be updated within a period no longer than 5 years, following the same methodology and rigor that was used for its development. The topics to be addressed may be reconsidered depending on the needs arising from clinical practice or the appearance of new evidence that should be included in the CPG.

Conflicts of interest

The following authors reported no conflicts of interest: SIC, EAS, DPF, LCNB, CHS, EPV, FEM, WC, JACG, SDM, CJE, IJG, SLC, JAD, NG, JEM, MP. The following authors reported a conflict of interest: JACL (Pfizer, Novo Nordisk), AS (Johnson & Johnson), JVT (Boehringer Ingelheim, GlaxoSmithKline), MCV (Pfizer), CAA (Merck Sharp & Dohme, Pfizer), ALL (Merck Sharp & Dohme, Pfizer), JEP (Procaps, GPC Pharma), IAR (Pfizer), FOG (Merck Sharp & Dohme, Pfizer, Fresenius Kabi), TE (Novo Nordisk), FG (Procaps).

Funding

This guideline was prepared within the framework of the project Programas de administración de antimicrobianos en un país latinoamericano (Antimicrobial stewardship programs in a Latin American country) of the Universidad Nacional de Colombia, whose objectives included the elaboration of a CPG for CAP management in the Colombian context. The project was financed by a grant from the International Society for Infectious Diseases (ISID) and Pfizer.

Acknowledgments

Patient representatives: José Ernesto Mosquera and Mildred Pérez, Asociación de Usuarios de Méderi.

Administrative support: Fabiam Andrés Ariza, Faculty of Medicine, Universidad Nacional de Colombia.

Editorial independence

The contents of this guideline were freely developed; there was no influence from ISID and/or Pfizer. All the steps considered in the methodology for the development of this guideline, from the creation of the GDG to the elaboration of the recommendations and writing of the final document, were carried out in their entirety and independently by the development group. The sponsors did not participate in any part of this process, nor did they have any influence over the contents of this document.

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Supplementary material

Supplementary Table 1. Medline search strategy.

1

exp community-acquired infections/

2

(community-acquired adj2 infection$).mp.

3

(community-acquired adj2 pneumonia).mp.

4

exp respiratory tract infections/.

5

(respiratory adj2 tract adj2 infection$).mp.

6

or/1-5

7

exp coronavirus/

8

exp coronavirus infections/

9

(corona$ adj2 infection$).mp.

10

((corona* or corono*) adj2 (virus* or viral* or virinae*)).ti,ab,kw.

11

or/7-10

12

6 not 11

13

exp practice guidelines as topic/

14

exp practice guideline/

15

(practice adj2 guide$).mp.

16

or/13-15

17

12 and 16

18

exp randomized controlled trials as topic/

19

exp randomized controlled trial/

20

exp Cohort Studies/

21

or/18-20

22

17 not 21

23

limit 22 to yr=”2015 -Current”

93814

Guía de práctica clínica

Clinical Practice Guideline for the management of community-acquired pneumonia

Guía de práctica clínica para el manejo de la neumonía adquirida en la comunidad

Jorge Alberto Cortés1,2 Sonia Isabel Cuervo-Maldonado1 Laura Cristina Nocua-Báez1 Martha Carolina Valderrama1 Edgar Alberto Sánchez1,3 Alfredo Saavedra1,3 July Vianneth Torres3 Diana Paola Forero3 Carlos Arturo Álvarez-Moreno1 Aura Lucía Leal4,5,6 Jairo Enrique Pérez7 Iván Arturo Rodríguez8 Fredy Orlando Guevara9,10 Carlos Humberto Saavedra1 Erika Paola Vergara1,2 Franco Eduardo Montúfar11 Tatiana Espinosa12 Walter Chaves13,14 Jorge Armando Carrizosa15 Sugeich Del Mar Meléndez1,16 Carmelo José Espinosa1,17 Felipe García-López18 Ingrid Jany Guzmán19 Sergio Leonardo Cortés19 Jorge Augusto Díaz20 Nathaly González21.

1 Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Medicina Interna - Bogotá D.C. - Colombia.

² Hospital Universitario Nacional de Colombia - Comité de Infecciones Asociadas a la Atención en Salud - Bogotá D.C. - Colombia.

³ Hospital Universitario Nacional de Colombia - Unidad de Neumología - Bogotá D.C. - Colombia.

4 Universidad Nacional de Colombia - Sede Bogotá - Facultad de Medicina - Departamento de Microbiología - Bogotá D.C. - Colombia.

5 Fundación Santa Fé de Bogotá - Departamento de Medicina Interna - Bogotá D.C. - Colombia.

6 Fundación Santa Fé de Bogotá - Departamento de Patología y Laboratorios - Bogotá D.C. - Colombia.

7 Fundación Cardioinfantil - Instituto de Cardiología - Bogotá D.C. - Colombia.

8 Hospital San Vicente Fundación Rionegro - Rionegro - Colombia.

9 Clínica Colsanitas - Clínica Reina Sofía - Departamento de Vigilancia, Control y Prevención de Enfermedades Infecciosas - Bogotá D.C. - Colombia.

10 Fundación Santa Fé de Bogotá - Sección de Enfermedades Infecciosas - Bogotá D.C. - Colombia.

11 Universidad de Antioquia - Clínica León XIII - Medellín - Colombia.

12 Clínica Cardiovascular del Caribe - Montería - Colombia.

13 Hospital de San José de Bogotá - Departamento de Medicina Interna - Bogotá D.C. - Colombia.

14 Fundación Universitaria de Ciencias de la Salud - Departamento de Medicina Interna - Bogotá D.C. - Colombia.

15 Fundación Santa Fé de Bogotá - Unidad de Cuidado Neurocrítico - Bogotá D.C. - Colombia.

16 Hospital Universitario Nacional de Colombia - Subdirección de Clínicas Médicas - Bogotá D.C. - Colombia.

17 Hospital Universitario Nacional de Colombia - Dirección de Cuidado Intensivo - Bogotá D.C. - Colombia.

18 Hospital Universitario Nacional de Colombia - Departamento de Auditoría - Bogotá D.C. - Colombia.

19 Hospital Universitario Nacional de Colombia - Dirección de Rehabilitación y Desarrollo Humano - Bogotá D.C. - Colombia.

20 Universidad Nacional de Colombia - Facultad de Ciencias - Departamento de Farmacia - Bogotá D.C. - Colombia.

21 Hospital Universitario Nacional de Colombia - Departamento de Enfermería - Bogotá D.C. - Colombia.Open access

Received: 22/02/2021

Accepted: 11/11/2021

Correspondencia: Jorge Alberto Cortés. Departamento de Medicina Interna, Facultad de Medicina, Universidad Nacional de Colombia y Servicio de Infectología, Hospital Universitario Nacional. Email: jacortesl@unal.edu.co.

Keywords: Clinical guidelines as Topic; Pneumonia; Respiratory tract infections; Community-Acquired Infections; Colombia (MeSH).

Palabras clave: Guías de Práctica Clínica como Asunto; Neumonía; Infecciones del sistema respiratorio; Infecciones comunitarias adquiridas; Colombia (DeCS).

How to cite: Cortés JA, Cuervo-Maldonado SI, Nocua-Báez LC, Valderrama MC, Sánchez EA, Saavedra A, et al. Clinical Practice Guideline for the management of community-acquired pneumonia. Rev. Fac. Med. 2022;70(2):e93814. English. doi: https://doi.org/10.15446/revfacmed.v70n2.93814.

Cómo citar: Cortés JA, Cuervo-Maldonado SI, Nocua-Báez LC, Valderrama MC, Sánchez EA, Saavedra A, et al. [Guía de práctica clínica para el manejo de la neumonía adquirida en la comunidad]. Rev. Fac. Med. 2022;70(2):e93814. English. doi: https://doi.org/10.15446/revfacmed.v70n2.93814.

Copyright: ©2021 Universidad Nacional de Colombia. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, the original author and source are credited.

Abstract

Pneumonia continues to be one of the main causes of consultation and hospitalization to which, besides its high impact on morbidity and mortality, the current problem of antimicrobial resistance is added; thus, establishing guidelines that allow its adequate diagnosis and treatment is of great importance to obtain better clinical outcomes and promote a rational use of antibiotics in these patients. This clinical practice guideline (CPG) contains evidence-based recommendations for the diagnosis and treatment of community-acquired pneumonia in adult population; these recommendations were made by means of the process of adaptation of evidence-based CPGs for the Colombian context.

Resumen

La neumonía sigue siendo una de las principales causas de consulta y de hospitalización a la que, además de su un alto impacto en términos de morbilidad y mortalidad, se suma la actual problemática de resistencia a los antimicrobianos, por lo que establecer directrices que permitan su adecuado diagnóstico y tratamiento es de gran importancia para obtener mejores desenlaces clínicos y promover un uso racional de antibióticos en estos pacientes. La presente guía de práctica clínica (GPC) contiene recomendaciones basadas en la evidencia para el diagnóstico y tratamiento de la neumonía adquirida en la comunidad en adultos, las cuales fueron realizadas mediante el proceso de adaptación de GPC basadas en la evidencia para el contexto colombiano.

Introducción

La neumonía es una infección que puede afectar uno o ambos pulmones y cuya sintomatología puede variar de leve a grave, incluyendo tos (con o sin mocos), fiebre, escalofríos y dificultad para respirar. El grado de severidad de la neumonía depende de factores como la edad, el estado de salud general y la causa de la infección.1 Si bien la neumonía puede afectar a personas de todas las edades, los grupos etarios con un mayor riesgo de desarrollar neumonía y de que esta sea grave son los niños de 2 años o menores y los mayores de 65 años.1

De hecho, se ha reportado que, en comparación con otros grupos etarios, la tasa global de mortalidad por neumonía más alta ocurre en las personas de 70 o más años, con 261 muertes por neumonía por cada 100 000 personas en 2017 para este grupo etario.2 Además, también para 2017, la tasa de mortalidad global por neumonía fue de 15 muertes por cada 100 000 personas.2

En Estados Unidos, en 2014 la neumonía fue el diagnóstico principal más común en pacientes hospitalizados (41.2% en pacientes en unidad de cuidados intensivos [UCI] y 36.6% en aquellos en hospitalización general) y las enfermedades respiratorias representaron la causa más frecuente de muerte en pacientes con dos o más visitas previas al servicio de urgencias (36.1%) y la segunda causa más común en aquellos con una visita previa al servicio de urgencias (25.9%).3

En Colombia, para 2010 la población de 80 o más años fue el grupo etario con las tasas anuales más altas de consulta y de hospitalización (873 consultas y 100 hospitalizaciones por cada 1 000 personas-año, respectivamente); además, la infección del tracto respiratorio inferior fue la enfermedad con la segunda tasa de incidencia anual más alta (2 232 casos nuevos por cada 100 000 personas).4

Además de su impacto en términos de morbilidad y mortalidad, y debido a que el uso de antimicrobianos es una de las opciones terapéuticas a considerar en el tratamiento de la neumonía, su adecuado diagnóstico y tratamiento tiene un impacto en el desarrollo de resistencia a los antimicrobianos, situación que, desde 2014, es considerada como un problema de salud pública por la Organización Mundial de la Salud (OMS),5 incluyendo en el listado de especies cuya resistencia a antimicrobianos es más preocupante a microorganismos adquiridos en la comunidad como Streptococcus pneumoniae, uno de los principales agentes etiológicos de la neumonía adquirida en la comunidad (NAC),6 definida como la infección aguda del parénquima pulmonar que se adquiere en un entorno comunitario y que no está asociada a la atención en salud en un entorno hospitalario, hogar de ancianos u otro centro de atención médica.7

Por lo anterior, es importante establecer directrices que permitan orientar el tratamiento de este grupo de pacientes y, de esta forma, obtener mejores desenlaces clínicos y promover un uso racional de antibióticos en este escenario. En Colombia, la última guía nacional para el manejo de la NAC fue publicada en 2013,8 por lo que a la fecha se requiere la revisión y actualización de las recomendaciones para el manejo de esta infección en el país, sin dejar de lado las recomendaciones específicas para la atención de pacientes COVID-19,9 las cuales, según la necesidad o aparición de nueva evidencia, podrán ser revisadas y actualizadas en el tiempo.

Alcance de la guía de práctica clínica (GPC)

Esta GPC está dirigida al personal de la salud involucrado en la atención de pacientes adultos (>18 años) con sospecha clínica o diagnóstico confirmado de NAC y a los tomadores de decisiones o entes involucrados en la generación de políticas en salud relacionadas con el manejo de esta condición. Esta GPC incluye recomendaciones para el diagnóstico y tratamiento de la NAC el contexto colombiano.

Objetivo de la guía de práctica clínica

Generar, de manera sistemática, recomendaciones clínicas basadas en la evidencia para el diagnóstico y tratamiento de pacientes adultos con sospecha clínica o diagnóstico confirmado de NAC para optimizar la calidad de la atención en salud prestada a estos pacientes en el país y, de esta forma, obtener mejores desenlaces clínicos y promover el uso adecuado y seguro de antimicrobianos en el tratamiento de esta población.

Población considerada en la GPC

Las recomendaciones contenidas en esta GPC incluyen los siguientes grupos de pacientes:

  • Pacientes adultos (>18 años)
  • Pacientes con sospecha clínica o diagnóstico confirmado de NAC.
  • Pacientes con sospecha clínica o diagnóstico confirmado de neumonía por aspiración.

Población no considerada en la GPC

Las recomendaciones contenidas en esta GPC no incluyen los siguientes grupos poblacionales:

  • Población pediátrica (<18 años de edad).
  • Gestantes
  • Pacientes con sospecha clínica o diagnóstico confirmado de neumonía asociada a la atención en salud.
  • Pacientes con sospecha clínica o diagnóstico confirmado de neumonía asociada a ventilación mecánica.
  • Pacientes con exacerbación aguda de enfermedad pulmonar obstructiva crónica.
  • Pacientes con inmunosupresión primaria o secundaria.

Usuarios a los que está dirigida la GPC

Las recomendaciones contenidas en la presente GPC están dirigidas a los profesionales de la salud involucrados en el proceso de atención en salud de pacientes adultos con sospecha clínica o diagnóstico confirmado de NAC en los diferentes niveles de atención en salud del Sistema General de Seguridad Social en Salud de Colombia (I, II, III y IV), a saber, médicos generales; especialistas en medicina de urgencias, medicina familiar, medicina interna, medicina crítica y cuidado intensivo, neumología e infectología; enfermeros profesionales; personal de laboratorio clínico; químicos farmacéuticos y demás personal implicado en el diagnóstico y tratamiento de pacientes con NAC.

Metodología

Esta GPC se desarrolló siguiendo los lineamientos establecidos en la Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia del Ministerio de Salud y Protección Social de Colombia,10 como se describe a continuación.

Conformación del grupo desarrollador de la guía

El grupo desarrollador de la guía (GDG) estuvo conformado por ocho miembros distribuidos de la siguiente manera: dos especialistas en enfermedades infecciosas en población adulta (JAC, SIC), cuatro especialistas en neumología en población adulta (EAS, AS, JVT, DPA), un especialista en medicina interna (LCN) y dos epidemiólogos clínicos con experiencia en el desarrollo de GPC, revisiones sistemáticas de la literatura, síntesis y calificación de la evidencia y en procesos participativos (JAC, MCV).

Previo al inicio del desarrollo de la GPC, cada uno de los miembros del GDG declaró si presentaba o no conflictos de interés mediante el diligenciamiento de un formulario de divulgación de conflictos de interés diseñado para tal fin. En los casos en que se declaró algún conflicto, se realizó el respectivo análisis para definir su implicación en la participación del miembro en las diferentes actividades de desarrollo de la GPC.

El alcance y los objetivos de la GPC, así como los aspectos a abordarse, fueron definidos en reuniones de consenso informales en las que participaron todos los miembros del GDG.

Búsqueda de GPC

Una vez definido el alcance y los objetivos de la GPC, se realizó una búsqueda sistemática de GPC para identificar guías publicadas en cualquier idioma entre 2015 y 2020 que abordaran los aspectos establecidos en el alcance de la presente guía.

Se realizaron búsquedas en los sitios web de los siguientes organismos compiladores y desarrolladores de GPC: Guidelines International Network, Agency for Healthcare Research and Quality/ National Guidelines Clearinghouse, CMA Infobase: Clinical Practice Guidelines, Catálogo de Guías de Práctica Clínica en el Sistema Nacional de Salud (Guía Salud), National Institute for Clinical Excellence (NICE, por su sigla en inglés), Scottish Intercollegiate Guidelines Network , New Zealand Guidelines Group y American College of Physicians.

También se realizaron búsquedas sistemáticas en MedLine, LILACS y Epistemonikos mediante estrategias de búsqueda adaptadas para cada motor de búsqueda utilizando operadores booleanos, de truncamiento y de proximidad, así como términos en texto libre y vocabulario controlado, empleando términos clave como ”community-acquired infections” y “respiratory tract infections”. La estrategia de búsqueda en Medline se muestra en la Tabla suplementaria 1.

Tamización, evaluación de la calidad y selección de las GPC a utilizar para la elaboración de la guía

Una vez realizadas las búsquedas, y luego de remover duplicados, dos revisores (MCV, LCN) realizaron de forma independiente la tamización primaria de los registros recuperados mediante la lectura de título y resumen, seleccionando aquellos documentos clasificados como GPC o recomendaciones basadas en la evidencia que abordaran al menos uno de los aspectos definidos en el alcance de la presente guía. Posteriormente, dos revisores (MCV, LCN) realizaron de forma independiente la tamización secundaria (lectura a texto completo) de las referencias seleccionadas en el paso anterior, usando la herramienta 7 modificada (i.e., Guideline Implementability Appraisal tool) propuesta en la Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia del Ministerio de Salud y Protección Social de Colombia;10 los desacuerdos sobre la inclusión de una GPC fueron resueltos por consenso o mediante la intervención de un tercer revisor en los casos en los que no se logró un acuerdo entre los dos revisores.

Si bien, como se mencionó antes, no hubo restricciones de idioma de publicación en las búsquedas de las GPC, en la etapa de tamización de lectura a texto completo se excluyeron los estudios publicados en idiomas como alemán, japonés o coreano y se tuvieron en cuenta solo aquellas publicadas en inglés o español, debido a que los revisores no dominaban los primeros idiomas.

Posteriormente, las GPC seleccionadas se presentaron al grupo desarrollador con el fin de evaluar su calidad metodológica mediante la herramienta AGREE II.11 Cada una de las guías fue evaluada por tres revisores de forma independiente, y siempre participó al menos un experto clínico y un experto metodológico en dicho proceso; además, en los casos en los que hubo dudas respecto a la información disponible para la evaluación de la GPC, mediante correo electrónico se solicitó información complementaria a los grupos desarrolladores.

Luego de completar el proceso de evaluación de calidad, se seleccionaron aquellas GPC con un puntaje ≥60% en los dominios de rigor metodológico y de independencia editorial. Finalmente, acorde a las recomendaciones de la Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia del Ministerio de Salud y Protección Social de Colombia,10 y con el objetivo de seleccionar las GPC a utilizar en el proceso de adaptación, el GDG analizó las guías seleccionadas teniendo en cuenta los siguientes aspectos: los temas abordados en la guía, el uso de la metodología GRADE, el año de publicación y la fecha de la última búsqueda de la evidencia reportada en la guía.

Con base en la metodología arriba descrita se seleccionaron dos GPC para el proceso de adaptación: La GPC de la Sociedad Torácica Americana y la Sociedad Americana de Enfermedades Infecciosas (ATS / IDSA, por su sigla en inglés): Diagnosis and Treatment of Adults with Community acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America12 y la GPC del National Institute for Clinical Excellence (NICE): Pneumonia (community-acquired): antimicrobial prescribing ng138,13 ambas publicadas en 2019. Para el proceso de adaptación de las recomendaciones al contexto colombiano se obtuvo la autorización de los autores de ambas GPC (Metlay JP y NICE).

Adaptación de las recomendaciones

El GDG realizó el proceso de adaptación usando la metodología GRADE, (específicamente la herramienta GRADE EtD,14,15 con base en la información proporcionada en las dos GPC seleccionadas e incluyendo los perfiles de evidencia GRADE, junto con la evaluación de la certeza de la evidencia realizada mediante el análisis de cada uno de los siguientes dominios: número y diseño de los estudios, riesgo de sesgo, inconsistencia, evidencia indirecta, imprecisión y otras consideraciones, y teniendo en cuenta las consideraciones específicas del contexto colombiano, los beneficios y daños de las diferentes opciones, el uso de recursos, el impacto en equidad y la factibilidad de su implementación.

Consenso de expertos

Las recomendaciones adaptadas fueron presentadas en tres reuniones de consenso de expertos y en las que participaron representantes de diferentes disciplinas de las ciencias de la salud y de diferentes sociedades científicas (Asociación Colombiana de Infectología - ACIN [JP, FOG, IR], Asociación Colombiana de Neumología y Cirugía del Tórax - Asoneumocito [FM], Asociación Colombiana de Medicina Interna - ACMI, Asociación Colombiana de Medicina Crítica y Cuidado Intensivo - AMCI [JARC], profesionales de las áreas de microbiología, terapia respiratoria, farmacia, enfermería y auditoria en salud [ALL, IJG, SLC, JAD, NG, FG]), así como representantes de los pacientes (Asociación de usuarios de Méderi [JEM, MP]), incluyéndose de esta forma la perspectiva de las diferentes partes interesadas.

En la reunión el consenso, mediante un proceso participativo con metodología Delphi en tiempo real, y teniendo en cuenta la información y evidencia proporcionadas por las dos GPC seleccionadas y las consideraciones específicas del contexto colombiano aportadas por los expertos clínicos, se formularon las recomendaciones, su graduación según la metodología GRADE16 y se generaron puntos de buena práctica, los cuales permiten una buena práctica clínica en el manejo de los pacientes.

La votación durante el consenso se realizó de forma anónima y por medio electrónico. Se definió que había acuerdo si más del 50% de los votantes estaban a favor o en contra de una recomendación o punto de buena práctica; en los casos en los que no hubo acuerdo en la primera ronda, se realizó una sesión de discusión y una nueva ronda de votación; se permitió un máximo de tres rondas de votación para cada recomendación y/o punto de buena práctica.

Niveles de certeza en la evidencia

  • Alta: el grupo está muy seguro de que el verdadero efecto se acerca a la estimación del efecto.
  • Moderada: el grupo tiene una confianza moderada en la estimación del efecto. Es probable que el efecto real se acerque a la estimación del efecto, pero existe la posibilidad de que sea sustancialmente diferente.
  • Baja: la confianza del grupo en la estimación del efecto es limitada. El efecto real puede ser sustancialmente diferente de la estimación del efecto.
  • Muy baja: el grupo tiene muy poca confianza en la estimación del efecto. Es probable que el efecto real sea sustancialmente diferente de la estimación del efecto.

Implicaciones de la fuerza de la recomendación

Las implicaciones de una recomendación fuerte son:

  • Para los pacientes: la mayoría de las personas en esta situación desearían el curso de acción recomendado y solo una pequeña proporción no lo haría.
  • Para los médicos: la mayoría de los pacientes deben recibir el curso de acción recomendado.
  • Para los responsables de la formulación de políticas: la recomendación se puede adoptar como política en la mayoría de situaciones.

Las implicaciones de una recomendación (sugerencia) débil (condicional) son:

  • Para los pacientes: la mayoría de las personas en esta situación desearían el curso de acción recomendado, pero muchas no.
  • Para los médicos: debe reconocer que diferentes opciones serán apropiadas para diferentes pacientes y que debe ayudar a cada paciente a llegar a una decisión de manejo coherente con sus valores y preferencias.
  • Para los formuladores de políticas: la formulación de políticas requerirá un debate sustancial y la participación de muchas partes interesadas.

Preguntas abordadas en la guía

1.¿Se debe realizar tinción de Gram y cultivo de esputo para el diagnóstico de NAC en adultos?

2.¿Se deben realizar hemocultivos para el diagnóstico de NAC en adultos?

3.¿Se deben realizar pruebas de antígeno urinario para el diagnóstico de NAC en adultos?

4.¿Se deben realizar pruebas para la detección de los virus de la influenza para el diagnóstico de NAC en adultos?

5.¿Se deben utilizar reglas de predicción clínica para determinar el escenario de atención en salud en el que los pacientes adultos con NAC deben recibir tratamiento?

6.¿Se debe utilizar la prueba de procalcitonina para definir el inicio del tratamiento con antimicrobianos en adultos con NAC?

7.¿Cuál es la mejor estrategia para el tratamiento antimicrobiano empírico en pacientes adultos ambulatorios con NAC?

8.¿Cuál es la mejor estrategia para el tratamiento antimicrobiano empírico en pacientes adultos hospitalizados con NAC?

9.¿Cuál es la mejor estrategia para el tratamiento antimicrobiano empírico en pacientes adultos hospitalizados con NAC y con factores de riesgo de Staphylococcus aureus resistente a meticilina (SARM) o Pseudomonas aeruginosa?

10.¿Cuál es la duración apropiada del tratamiento antimicrobiano en pacientes adultos con NAC, tanto ambulatorios, como hospitalizados?

11.¿Cuál es la vía de administración adecuada del tratamiento antimicrobiano en pacientes adultos con NAC moderada a grave?

12.¿Se debe incluir terapia antiviral en el tratamiento de pacientes adultos con NAC que dan positivo en la prueba de influenza?

13.¿Se deben usar corticosteroides en pacientes adultos hospitalizados con NAC?

Recomendaciones y revisión de la evidencia

Diagnóstico microbiológico

Pregunta Nº 1. ¿Se debe realizar tinción de Gram y cultivo de esputo para el diagnóstico de NAC en adultos?

Recomendaciones

  • No recomendamos realizar tinción de Gram y cultivo de esputo de forma rutinaria en pacientes adultos ambulatorios con NAC (fuerza de la recomendación: fuerte en contra; calidad de la evidencia: muy baja ◯◯◯).
  • Recomendamos realizar tinción de Gram y cultivo de secreciones del tracto respiratorio inferior antes de iniciar el tratamiento antimicrobiano en pacientes adultos hospitalizados con NAC que:
    • Hayan sido diagnosticados con NAC grave (Tabla 1) (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: muy baja ⨁◯◯◯);
    • Estén recibiendo terapia antimicrobiana empírica para SARM o P. aeruginosa (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: muy baja ⨁◯◯◯); o
    • Tengan antecedente de infección por SARM o P. aeruginosa, especialmente aquellos con infección previa del tracto respiratorio por uno de estos patógenos (fuerza de la recomendación: débil a favor; calidad de la evidencia: muy baja ⨁◯◯◯); o
    • Tengan antecedente de hospitalización y terapia antimicrobiana en los últimos 90 días (fuerza de la recomendación: débil a favor; calidad de la evidencia: muy baja ◯◯◯).

Tabla 1. Criterios de severidad de la neumonía adquirida en la comunidad.

Criterios menores

Frecuencia respiratoria ≥30 respiraciones por minuto

Relación PaO2 / FiO2 ≤250

Infiltrados multilobares

Confusión / desorientación

Uremia (nivel de nitrógeno ureico en sangre ≥20 mg/dl)

Leucopenia (recuento de glóbulos blancos <4000 células/ml)

Trombocitopenia (recuento de plaquetas <100.000 / ml)

Hipotermia (temperatura central <36° C)

Hipotensión que requiere reanimación intensiva con líquidos

Criterios mayores

Choque séptico con necesidad de terapia vasopresora

Insuficiencia respiratoria que requiere ventilación mecánica

Se considera que la NAC es grave si el paciente cumple con 1 criterio mayor o 3 o más menores.

Fuente: Adaptado de Mandell et.al.17

Punto de buena práctica clínica

Se deben establecer parámetros de calidad de la muestra del tracto respiratorio de acuerdo con los criterios de Murray & Washington,18 con interpretación del informe solo si el resultado de la muestra es de categoría 2 o 3. Ver Tabla 2.

Tabla 2. Criterios de Murray y Washington.

Células escamosas por campo de visión del microscopio

0

1-9

10-24

Más de 25

Neutrófilos por campo

0

3

0

0

0

1-9

3

0

0

0

20-24

3

1

0

0

Más de 25

3

2

1

0

Fuente: Adaptado de Murray & Washington.18

Justificación de la recomendación

La tinción de Gram es una prueba que puede realizarse de forma fácil y rápida en la mayoría de instituciones de salud, incluso en aquellas de baja complejidad. Diseñada inicialmente para identificar S. pneumoniae, permite determinar de forma rápida la etiología microbiana de la NAC. Por el contrario, el cultivo de esputo conlleva una mayor dificultad debido a las limitaciones usuales para el crecimiento de S. pneumoniae y un número importante de microorganismos causales, especialmente los intracelulares.

En la práctica clínica, de acuerdo con lo reportado en la literatura, en el escenario ambulatorio, el resultado de la tinción de Gram o del cultivo de esputo puede tener un impacto muy limitado sobre las decisiones relacionadas con el tratamiento de la NAC. Debido a la baja calidad de la evidencia del beneficio de realizar cultivos de las muestras respiratorias de pacientes adultos con NAC en el escenario ambulatorio, el grupo de consenso acordó realizar la recomendación en contra de la realización de tinción de Gram y cultivo de esputo en este escenario. Sin embargo, en dos casos sí se recomienda la realización de cultivo y de tinción de Gram del esputo: el primero, cultivo de aspirado endotraqueal en pacientes con NAC grave que requieren cuidado intensivo con intubación endotraqueal, pues McCauley et al.19 encontraron que, en pacientes entubados con NAC, el cultivo de aspirado traqueal fue la única prueba positiva en 39% de los casos (32 de 89) en los que otras pruebas diagnósticas como hemocultivos y pruebas de antígenos urinarios fueron negativas.

El segundo caso en el que recomendamos realizar cultivo y tinción de Gram de esputo es en aquellos pacientes que se sospeche infección por SAMR o P. aeruginosa para confirmar esta etiología y/o ajustar el tratamiento antibiótico según los resultados de estas pruebas; si bien la evidencia sobre los factores de riesgo asociados con la presencia de estos microorganismos tampoco es sólida, se ha reportado que situaciones como tener antecedente de infección por estas bacterias y haber recibido tratamiento antibiótico o haber estado hospitalizado en los últimos 90 días pueden estar relacionados con un mayor riesgo de presencia de SAMR o P. aeruginosa.

Además, en hospitales de referencia, la realización de cultivos de esputo al ingreso puede ayudar en la toma decisiones relativas al manejo antimicrobiano en estos pacientes, así como identificar aquellos que han ingresado con colonización previa de la vía aérea. Con esta recomendación se busca promover el uso racional de antimicrobianos en el manejo de este paciente, al permitir el ajuste del esquema antimicrobiano una vez se obtienen los resultados del cultivo.

Resumen de la evidencia

Los estudios identificados para establecer estas recomendaciones son observacionales y, en general, la calidad de la evidencia es muy baja. En primer lugar, se establecen los criterios para diferenciar a los pacientes que tienen NAC grave (Tabla 1),17 mientras que en la Tabla 2 se presentan los criterios de Murray y Washington para interpretar la tinción de Gram de esputo.18 Signori et al.,20 en un estudio realizado en 274 pacientes hospitalizados con NAC, evaluaron la frecuencia de uso del cultivo de esputo y su asociación con la mortalidad, encontrando una mortalidad del 32.7% en los pacientes que no presentaron expectoración (n=58), del 20.9% en aquellos que tuvieron expectoración pero en los que no se recolectaron muestras de esputo para cultivo de esputo (n=124) y de 6.5% en los que se obtuvo muestra del esputo (n=92), con un riesgo de mortalidad mayor en el grupo con expectoración pero en los que no se recolectó muestra de esputo (OR: 3.78; IC95%: 1.40-10.23). Por otra parte, en la investigación de Uematsu et al.,21 realizada en Japón con datos de 65 141 pacientes adultos hospitalizados con NAC, no se encontró una asociación entre la realización de pruebas de esputo y la mortalidad a 30 días (OR: 1.06; IC95%: 0.98-1.15; p= 0.013), ni con la duración de la estancia hospitalaria (HR: 0.98; IC95%: 0.97-1.00; p= 0.071).

Estudios sobre la utilidad de la tinción de Gram de esputo en el escenario hospitalario, como el realizado en Japón por Sato et al.22 en 144 casos de NAC que requirieron hospitalización, han mostrado que no hay una diferencia significativa en la duración de la estancia hospitalaria (9.67 días con la prueba vs. 11.75 días sin la prueba, p=0.053) ni en el tiempo de terapia antibiótica intravenosa (6.73 días con la tinción de Gram del esputo vs. 7.91 días sin la prueba, p=0.44). Estos hallazgos han sido confirmados en otros estudios sobre pruebas microbiológicas que han demostrado que establecer un diagnóstico etiológico mediante tinción de Gram o cultivo de esputo de manera rutinaria en escenarios con una baja frecuencia de patógenos resistentes no tiene un impacto significativo en la mortalidad, la duración de la estancia hospitalaria, cambios en el tratamiento antimicrobiano, ni en el pronóstico clínico general de estos pacientes.23,24

En Colombia no hay suficiente información para evaluar el impacto económico de la implementación de estas recomendaciones. En la literatura existente no se identificaron datos locales sobre los costos de la atención médica de la NAC. Si bien durante la reunión de consenso se tuvieron en cuenta los datos de costos de algunos insumos, medicamentos, hospitalización, entre otros factores involucrados en la atención de estos pacientes en el país, no fue posible hacer una verdadera evaluación de la costo-efectividad de las recomendaciones. Tampoco se encontraron estudios que permitan evaluar, desde cualquier perspectiva, el efecto de las recomendaciones sobre la equidad en salud en poblaciones minoritarias o desfavorecidas. Estos dos aspectos se identificaron como puntos a investigar en Colombia para establecer de una mejor forma potenciales recomendaciones en futuras versiones de la guía.

Pregunta Nº 2. ¿Se deben realizar hemocultivos para el diagnóstico de NAC en adultos?

Recomendaciones

  • No recomendamos realizar hemocultivos en pacientes adultos ambulatorios con NAC (fuerza de la recomendación: fuerte en contra; calidad de la evidencia: ⨁◯◯◯).
  • Recomendamos realizar hemocultivos antes de iniciar el tratamiento antimicrobiano en pacientes adultos hospitalizados con NAC que:
    • Hayan sido diagnosticados con NAC grave (Tabla 1) (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: muy baja ⨁◯◯◯); o
    • Tengan factores de riesgo para SAMR o P. aeruginosa (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: muy baja ⨁◯◯◯); o
    • Tengan antecedente de infección por SAMR o P. aeruginosa, especialmente aquellos con infección previa del tracto respiratorio por uno de estos patógenos (fuerza de la recomendación: débil a favor; calidad de la evidencia: muy baja ⨁◯◯◯); o
    • Tengan antecedente de hospitalización y terapia antimicrobiana en los últimos 90 días (fuerza de la recomendación: débil a favor; calidad de la evidencia: muy baja ⨁◯◯◯).

Punto de buena práctica

El conjunto de hemocultivo se debe recolectar de acuerdo con los parámetros definidos en el manual de procedimientos para la toma de muestras del Instituto Nacional de Salud.25

Justificación de la recomendación

Los hemocultivos permiten identificar microorganismos presentes en la sangre al momento del diagnóstico de NAC. Sin embargo, la gran mayoría de pacientes no se presentarán con bacteriemia y esta última se limita a infecciones por S. pneumoniae, S. aureus y enterobacterias y a pacientes con comorbilidades o formas graves de la enfermedad.

La evidencia sobre el beneficio de la realización de hemocultivos en todos los pacientes con NAC es de muy baja calidad, por lo que la recomendación se ha limitado a ciertos grupos de pacientes que podrían considerarse de mayor riesgo, como aquellos con NAC grave o con factores de riesgo para microorganismos como SAMR o P. aeruginosa. Además, la realización rutinaria de esta prueba puede llevar a falsos positivos que promuevan el uso indiscriminado de antimicrobianos en el contexto del tratamiento de la NAC. Otra razón para no recomendar la realización rutinaria de hemocultivos es que los resultados pueden demorar más de 48 horas, por lo que el ajuste del tratamiento podría ser tardío o ya no ser relevante en pacientes ambulatorios o en aquellos hospitalizados, pero con NAC leve o moderada.

Resumen de la evidencia

Los estudios sobre la utilidad y beneficio de la toma de hemocultivos en pacientes con NAC que fueron revisados son de naturaleza observacional. Por ejemplo, Meehan et al.,26 en un estudio en el que se evaluó cuáles estrategias de cuidado en pacientes hospitalizados con NAC se asociaron con el desenlace de mortalidad en una muestra de 14 069 adultos mayores (≥65 años) hospitalizados en diferentes partes de Estados Unidos, encontraron que la realización de hemocultivos, tanto antes de iniciar la administración de antibióticos, como durante las primeras 24 horas de la administración, no mostró un beneficio respecto a la mortalidad a 30 días (OR ajustado: 0.92, IC95%: 0.82-1.02; p=0.10 y OR ajustado: 0.90, IC95%: 0.81-1.00, p=0.07).

Igualmente, otro estudio realizado en Estados Unidos en 1 062 pacientes adultos hospitalizados con NAC, reportó, por un lado, que la realización de hemocultivos dentro de las primeras 24 horas al ingreso hospitalario o antes de la administración de antimicrobianos no tuvo ningún impacto en la mortalidad (OR ajustado: 0.86; IC95%: 0.36-2.07 y OR ajustado: 1.21; IC95%: 0.62-2.34, respectivamente), ni en el tiempo de estancia hospitalaria (OR ajustado: 1.04; IC95%: 0.72-1.50 y OR ajustado: 0.84; IC95%: 0.60-1.17, respectivamente), pero, por el otro, que sí hubo una relación entre realizar hemocultivos durante las primeras 24 horas posterior al ingreso hospitalario y un mayor riesgo de inestabilidad clínica a las 48 horas (OR ajustado: 1.62; IC95%: 1.13-2.33).27

De forma similar, Costantini et al.,28 en un estudio en el que compararon dos cohortes de pacientes con NAC admitidos a un hospital de Italia en 2005 (n=234) y 2012 (n=321), encontraron que la realización de esta prueba no se asoció con un beneficio en la mortalidad intrahospitalaria (OR: 0.67; IC95%: 0.37-1.21), ni en la mortalidad a 30 días (OR: 0.6; IC95%: 0.32-1.09). Finalmente, se ha descrito que, en el contexto de la realización rutinaria de hemocultivos en pacientes con NAC no grave, la tasa de hemocultivos contaminados es de 3.1% y que, por tanto, es probable que haya muchos más falsos positivos (p. ej., el crecimiento de microorganismos estafilococos coagulasa negativos que colonizan la piel de los pacientes y no están relacionados con la NAC) que verdaderos positivos, lo que promovería el uso indiscriminado de antibióticos en el manejo de estos pacientes.29

Pregunta Nº 3. ¿Se deben realizar pruebas de antígeno urinario para el diagnóstico de NAC en adultos?

Recomendaciones

  • Sugerimos realizar la prueba de antígeno urinario neumocócico en adultos con NAC grave (Tabla 1) (fuerza de la recomendación: débil a favor; calidad de la evidencia: ⨁⨁◯◯).

Justificación de la recomendación

Los ensayos clínicos aleatorizados sobre la realización de pruebas de antígeno urinario para la detección de Legionella y S. pneumoniae no han mostrado un claro beneficio en términos de desenlaces clínicos en pacientes con NAC grave que requieren manejo en UCI. Por otra parte, los estudios observacionales lamentablemente son de baja calidad y sus resultados son, con frecuencia, contradictorios: en algunos se plantea que realizar prueba de antígeno urinario para la detección Legionella se relaciona con una disminución de la mortalidad en pacientes hospitalizados con NAC, mientras que otros concluyen que no hay tal beneficio.

Además, no se encontraron trabajos que evaluaran únicamente el papel de las pruebas de antígeno urinario en pacientes hospitalizados con NAC grave; en su lugar, los estudios incluyen otras pruebas diagnósticas de laboratorio y múltiples estrategias de cuidado, por lo que no es claro si los resultados se pueden atribuir solo a la realización de pruebas de antígeno urinario o al conjunto de las estrategias diagnósticas y terapéuticas. Aunque la infección por Legionella representa una alta carga en términos de mortalidad en el escenario de la NAC grave, consideramos que el beneficio de realizar la prueba de antígeno urinario para determinar su presencia es muy limitado teniendo en cuenta que este microorganismo ya estaría cubierto por el esquema del tratamiento antimicrobiano empírico instaurado en los pacientes con NAC considerados de alto riesgo. Respecto a la realización de la prueba de antígeno urinario neumocócico, el grupo de consenso acordó recomendar esta práctica en pacientes con NAC grave, ya que se ha reportado que su uso pueda estar relacionado con una disminución en la mortalidad.28

Resumen de la evidencia

La evidencia sobre el uso de pruebas de antígeno urinario para la detección de microorganismos en el diagnóstico de la NAC es contradictoria. Por ejemplo, Costantini et al.28 encontraron que la toma de estas pruebas, incluyendo las pruebas de antígeno urinario para neumococo y legionella, se asoció con una disminución en la mortalidad intrahospitalaria y en la mortalidad a 30 días (OR: 0.427; IC95%: 0.215-0.850 y OR: 0.341; IC95%: 0.170-0.685, respectivamente), hallazgo también reportado por Uematsu et al.21 para lo mortalidad a 30 días (OR: 0.75, IC95%: 0.69-0.82; p<0.001).

Por otra parte, Falgera et al.,30 en un estudio realizado en 177 pacientes hospitalizados con NAC y en el que se evaluó el impacto de una estrategia de tratamiento basada en el resultado de la prueba de antígeno urinario (n=88) en comparación con el tratamiento empírico (n=89), evidenciaron, en el análisis comparativo por intención de tratamiento, que la realización de esta prueba no mostró ningún beneficio en términos de mortalidad, recaída clínica, admisión a UCI, días de estancia hospitalaria, necesidad de readmisión, eventos adversos, duración (en días) del tratamiento antimicrobiano y duración (en días) del tratamiento por vía intravenosa.

Pregunta Nº 4 ¿Se deben realizar pruebas para la detección de los virus de la influenza para el diagnóstico de NAC en adultos?

Recomendaciones

Recomendamos realizar pruebas para la detección de virus de la influenza, de preferencia ensayos moleculares de detección de ácido nucleico o ARN viral de la influenza, en lugar de la prueba rápida de antígeno de influenza, en pacientes:

  • Diagnosticados con NAC grave (Tabla 1) (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: moderada ⨁⨁⨁◯), o
  • Que tengan una comorbilidad (respiratoria, cardiovascular o inmunosupresión) (Fuerza de la recomendación: fuerte a favor; calidad de la evidencia: moderada ⨁⨁⨁◯).

Justificación de la recomendación

La evidencia encontrada sobre la utilidad de las pruebas para la detección de los virus de la influenza en pacientes con NAC es escasa; además, los resultados reportados son controversiales. La información disponible proviene de estudios realizados en pacientes con infección respiratoria del tracto inferior, en un grupo de individuos con NAC, y no en una población de pacientes infectados únicamente con influenza. En estudios epidemiológicos se ha reportado que el pronóstico de los pacientes con NAC grave o con NAC y comorbilidades empeora cuando tienen una infección causada por uno de los virus de la influenza, por lo que el grupo de consenso decidió recomendar la realización de ensayos moleculares de detección de ácido nucleico o ARN viral de la influenza en estos dos escenarios clínicos.

Resumen de la evidencia

No encontramos estudios que evaluaran la utilidad de las pruebas para la detección de los virus de la influenza en pacientes con NAC, los pocos trabajos encontrados se realizaron en individuos con infección del tracto respiratorio inferior, como el ensayo clínico aleatorizado realizado por Oosterheert et al.31 en 107 pacientes (51.4% con NAC) para evaluar la viabilidad e impacto clínico y económico de usar la prueba de PCR TaqMan para la detección de virus respiratorios y patógenos atípicos, y en donde se encontró que, en comparación con el grupo control (n=52; uso de procedimientos diagnósticos convencionales) no hubo cambios en la mortalidad a 28 días, la duración del tratamiento antimicrobiano, ni la duración de la estancia hospitalaria.

Tratamiento

Pregunta Nº 5. ¿Se deben utilizar reglas de predicción clínica para determinar el escenario de atención en salud en el que los pacientes adultos con NAC deben recibir tratamiento?

Recomendaciones

  • Recomendamos utilizar el juicio clínico, junto con una regla de predicción clínica validada, ya sea el pneumonia severity index (PSI) o las escalas de severidad de la neumonía CURB-65 o CRB-65, para evaluar la severidad de la enfermedad y determinar la necesidad de hospitalización en adultos diagnosticados con NAC (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: baja ⨁⨁◯◯).

Puntos de buena práctica

  • Se debe utilizar el juicio clínico, junto con los criterios de severidad de la neumonía IDSA/ATS 2007, para determinar el nivel de atención en hospitalización en adultos con diagnóstico de NAC que no requieren vasopresores o ventilación mecánica.
  • Los adultos con NAC y con hipotensión que requieran terapia vasopresora o con insuficiencia respiratoria que requieran ventilación mecánica deben ser ingresados directamente a la UCI.

Justificación de la recomendación

El uso de reglas de predicción clínica para determinar el lugar en que se deben tratar los pacientes con NAC (escenario ambulatorio, hospitalización en sala general o UCI) ha demostrado ser más efectivo y seguro que el juicio clínico, disminuyendo la variabilidad en esta decisión entre los trabajadores de la salud. En el caso de los pacientes con NAC clasificados para tratamiento y seguimiento ambulatorio se ha reportado una disminución en los costos de atención y en el desarrollo de complicaciones asociadas con el tratamiento hospitalario.

A pesar que el rendimiento de las escalas de severidad y de predicción clínica puede variar, pues, dependiendo de su nivel de atención, no todas las instituciones de salud disponen de las pruebas de laboratorio y de diagnóstico requeridas para calcular los puntajes de estas escalas, recomendamos usar una de estas escalas, sin ninguna preferencia en particular, para determinar el escenario de atención en salud en el que se debe brindar el tratamiento de estos pacientes. En todo caso, además del uso de escalas de predicción clínica, la decisión debe tomarse teniendo en cuenta el juicio clínico, lo que incluye la variabilidad de los aspectos considerados en las reglas de predicción y factores sociodemográficos, económicos y de la red de apoyo del paciente.

Resumen de la evidencia

Las reglas de predicción clínica como las escalas de severidad de la neumonía PSI y CURB65 usan variables demográficas y datos clínicos obtenidos a partir de estudios de laboratorio y diagnósticos para determinar el pronóstico de los pacientes con NAC, especialmente el desenlace de mortalidad a 30 días.32-34 Al respecto, Marrie et al.,35 en un ensayo clínico controlado multicéntrico realizado en 1 743 pacientes con NAC que asistieron al servicio de urgencias para determinar si una estrategia de cuidado crítico que incluía reglas de predicción clínica tuvo beneficios en el tratamiento de estos pacientes, encontraron que usar el PSI fue una estrategia superior en términos de clasificar a los pacientes que requerían tratamiento ambulatorio en comparación con no utilizar ninguna regla de predicción clínica, y que el uso de esta escala también mostró un beneficio en cuanto la duración de la estancia hospitalaria, con una reducción de la readmisión hospitalaria. Estos hallazgos han sido confirmados en otros trabajos que han demostrado que el uso del PSI en esta población es seguro, especialmente para la selección de pacientes que solo requieren cuidado ambulatorio, y que esta escala tiene un mayor poder discriminativo para definir el lugar inicial de tratamiento de los pacientes con NAC, sin que el riesgo de mortalidad o morbilidad aumente.36,37

Los estudios sobre otras reglas de predicción clínica en neumonía son más escasos y sus resultados son menos consistentes; por ejemplo, en el caso de la escala CURB65, un ensayo aleatorizado realizado en Nueva Zelanda y en el que se comparó un grupo de pacientes con NAC que recibieron tratamiento hospitalario en sala general (n=25) con un grupo en el que se realizó tratamiento ambulatorio (n=24), tuvo limitaciones para determinar las diferencias entre ambas estrategias de manejo, una de ellas relacionadas con la administración intravenosa de antimicrobianos bajo la supervisión de personal de enfermería en el ambiente ambulatorio, práctica que corresponde al escenario hospitalario y que en varias regiones se denomina “hospitalización domiciliaria”.38

La escala CURB65 incluye variables sencillas que pueden ser registradas de manera rutinaria en la historia clínica, sin requerir la realización de pruebas de laboratorio adicionales aparte del examen de nitrógeno ureico en sangre, lo que facilita su uso en escenarios de menor nivel de complejidad de atención en salud y la convierte en una herramienta más fácil de usar en comparación con otras reglas de predicción clínica.39 En este sentido, Aujeski et al.,40 en un estudio realizado en 3181 pacientes con NAC atendidos en los servicios de urgencias de 32 hospitales de Estados Unidos y en el que se evaluó el rendimiento de las reglas de predicción clínica PSI, CURB65 y CURB para predecir la mortalidad a 30 días, encontraron que el rendimiento diagnóstico del PSI fue superior con una curva ROC de 0.81 (IC95%: 0.78-0.84), mostrando una diferencia significativa (p<0.01) en la comparación con las otras dos escalas (CURB: AUC=0.73, IC95%: 0.68-0.76; CURB65: AUC=0.76, IC 95%: 0.73-0.80).

Pregunta Nº 6. ¿Se debe utilizar la prueba de procalcitonina para definir el inicio del tratamiento con antimicrobianos en adultos con NAC?

Recomendaciones

  • No recomendamos realizar prueba de procalcitonina sérica (PCT) en adultos con NAC clínicamente sospechada y confirmada por estudios de imagen para, con base en los resultados de la prueba, decidir el inicio de la terapia antimicrobiana (fuerza de la recomendación: fuerte en contra; calidad de la evidencia: moderada ⨁⨁⨁◯).

Justificación de la recomendación

Algunos de los estudios que han descrito el uso de la prueba de PCT para establecer el inicio del tratamiento antimicrobiano en pacientes con NAC no cumplen claramente con los criterios diagnósticos de neumonía, incluso algunos no incluyen la realización de un estudio de imagen para confirmar el diagnóstico, por lo que es posible que los resultados sobre el beneficio de realizar esta prueba en estos pacientes no sean suficientemente confiables y las conclusiones sean controvertidas, siendo este último el factor de mayor peso por el que el GDG no recomendó realizar la PCT para decidir el inicio de la terapia antibiótica, ya que en varios ensayos clínicos, pacientes con valores de PCT por debajo del punto de corte de este marcador sérico y en los que no se ha iniciado tratamiento antimicrobiano presentan desenlaces favorables, mientras que otros pacientes con las mismas características no presentan una evolución clínica similar.

Sumado a lo anterior, también se tuvieron en cuenta otros factores que, con base en la experiencia de los expertos del grupo consenso, no justifican el uso de este examen en este contexto, tales como su costo, que no es una prueba que se encuentre fácilmente disponible en los diferentes niveles de atención en salud y que en algunas instituciones de salud el reporte de los resultados suele ser demorado (hasta 72 horas).

Resumen de la evidencia

Varios estudios han tratado de establecer un punto de corte confiable del nivel de la PCT sérica para diferenciar una NAC de etiología viral de una de origen bacteriano, pero hasta ahora no se ha podido establecer un umbral estándar; sin embargo, sí es claro que entre más alto el valor, más probabilidad de que el origen sea bacteriano.41 Algunos trabajos sobre el papel de este biomarcardor en el contexto de la NAC han sido realizados en pacientes con infección del tracto respiratorio inferior, como el estudio realizado en Suiza por Christ-Crain et al.42 en 243 pacientes (35.40% con NAC), y en el que se encontró que en el grupo en el que se usó la prueba de PCT (n=124) el riesgo relativo (RR) ajustado de exposición a antibióticos fue de 0.49 (IC 95%: 0.44-0.55; p<0.0001) en comparación con el grupo estándar ( solo juicio clínico); sin embargo, no se evaluaron otros desenlaces clínicos como mortalidad, duración de la estancia hospitalaria o desarrollo de complicaciones.

Similarmente, un ensayo clínico aleatorizado controlado realizado en Suiza en 302 pacientes con diagnóstico de NAC reportó que el uso de los niveles de PCT redujo la exposición a antibióticos (RR: 0.52, IC95%: 0.48-0.55; p<0.01), las prescripciones de antibióticos al ingreso (85 vs. 99%; p<0.01) y la duración del tratamiento con antibióticos (mediana: 5 vs. 12 días; p<0.01), pero, de nuevo, no se evaluaron desenlaces clínicos de pronóstico, ni el tiempo de hospitalización o el riesgo de falla clínica.43 En lo que respecta a la evaluación del impacto de usar este biomarcador en términos de efectos adversos, Schuetz et al.,44 en un ensayo clínico controlado aleatorizado realizado en 1359 pacientes con infección del tracto respiratorio inferior admitidos a los servicios de urgencias de 6 hospitales de Suiza, 68.1% de los cuales tenían NAC, encontraron que, teniendo en cuenta la reducción en la duración del tratamiento antibiótico, los pacientes del grupo de PCT (n=671) tuvieron un menor riesgo de eventos adversos relacionados con el uso de antibióticos, pero que, en lo que respecta a los desenlaces no deseables de muerte, ingreso a UCI, complicaciones específicas de la enfermedad o infección recurrente que requiriera uso de antibióticos durante los últimos 30 días, el uso de un algoritmo de PCT no fue superior al uso de estrategias de manejo basadas en el juicio clínico.

Además, se deben tener en cuenta las limitaciones para su implementación en Colombia, ya que la prueba de PCT no se encuentra disponible en todas las instituciones de salud y su uso está ampliamente limitado por no estar incluida en el plan de beneficios en salud (PBS), por lo que, considerando la importancia de iniciar el tratamiento antimicrobiano de forma oportuna, su uso podría implicar un retardo en el inicio de la administración de antibióticos en pacientes que lo requieran.

Pregunta Nº 7. ¿Cuál es la mejor estrategia para el tratamiento antimicrobiano empírico en pacientes adultos ambulatorios con NAC?

Recomendaciones

  • Recomendamos usar amoxicilina o, en caso de alergia a la penicilina, doxiciclina o claritomicina, en pacientes adultos diagnosticados con NAC tratados en el escenario ambulatorio y sin factores de riesgo para SAMR o P aeruginosa (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: moderada⨁⨁⨁◯).

Punto de buena práctica

Se debe evitar el uso de quinolonas en el tratamiento de la NAC.

Justificación de la recomendación

Para esta recomendación el grupo de consenso consideró estudios realizados en pacientes con NAC tratados en el escenario ambulatorio. Para establecer el tratamiento antimicrobiano de primera línea se tuvieron en cuenta los microorganismos etiológicos más frecuentes en esta población; los esquemas de tratamiento antimicrobiano propuestos no incluyen el cubrimiento de bacterias atípicas debido a que no se han reportado desenlaces perjudiciales en pacientes con NAC en tratamiento con amoxilicina. Otro aspecto a favor del uso de amoxicilina en monoterapia es que hay un amplio número de estudios sobre la seguridad de usar este antimicrobiano.

En los casos en que hay una contraindicación para el uso de amoxicilina, como tener antecedente de alergia a este antibiótico, el grupo de consenso recomendó la administración de doxiciclina o claritromicina; estos antimicrobianos no fueron considerados en el tratamiento de primera línea por dos motivos: primero, los efectos adversos adicionales de los macrólidos relacionados, en particular, con cambios electrocardiográficos, arritmias y mayor riesgo de muerte súbita, y segundo, para promover el uso racional de antimicrobianos en este escenario clínico.45

Por último, teniendo en cuenta que el uso de quinolonas aumenta el riesgo de inducción de resistencia a antimicrobianos en cocos Gram positivos y enterobacterias, que es un medicamento que se usa en el tratamiento de segunda línea para la tuberculosis, enfermedad endémica en Colombia, y la frecuencia y gravedad de los efectos adversos relacionados con la administración de estos antibióticos,46,47 como punto de buena práctica se debe evitar el uso de este grupo de medicamentos para el tratamiento de la NAC. La prescripción de los antimicrobianos debe estar basada en el perfil epidemiológico de susceptibilidad a antibióticos de los microorganismos causantes de NAC en cada institución de salud. Ver la Tabla 348-52 y la Tabla 4.

Tabla 3. Frecuencia de microorganismos causantes de NAC en Colombia.

Microorganismo

n * 7648

n* 31149

n* 13850

n+ 4851

n++ 6652

%

%

%

%

%

Bacterias

Streptococcus pneumoniae

36

27.6

16

23.4

12.5

Staphylococcus aureus

2

2.6

2.17

6.4

2.1

Staphylococcus spp. estafilococos coagulasa negativos

2.2

1.45

2.13

4.2

Haemophilus influenzae

10

2.2

1.45

2.13

4.2

Enterobacteriaceae

3.5

3.5

2.9

14.9

6.2

P. aeruginosa y Acinetobacter baumanii

1

4.26

4.2

Moraxella catarrhalis

0.3

Bacterias atípicas

Mycoplasma pneumoniae

22

13.8

8.56

12.5

Legionella pneumophila

1.9

2.9

2.13

2.1

Coxiella burnetii

5.8

2.13

4.2

Chlamydophila pneumoniae

1.3

8.7

2.13

4.2

Virus

Virus de la influenza A y B

10

1.9

10.6

16.7

Adenovirus

7.1

8.51

10.4

Virus sincitial respiratorio

4.2

0.72

8.51

6.2

Virus parainfluenza 1, 2 y 3

1.9

0.72

8.13

2.1

Micobacterias

Mycobacterium tuberculosis

2.9

0.72

Otros

Etiología mixta

22.8

8.7

19.7

20.8

Etiología desconocida

31.5

34

55.8

48.5

33.3

n*: Número de pacientes.

n+: número de adultos de 65 años o mayores.

n++ Número de adultos con NAC severa.

Fuente: Elaboración propia.

Tabla 4. Antimicrobianos y dosificaciones recomendadas para el tratamiento de pacientes adultos con NAC.

Antimicrobiano

Dosis

Intervalo

Observación

Ajuste renal

Orales

Amoxicilina

500 mg-1g

8 horas

Doxicilina

100 mg

12 horas

Dosis de carga de 200 mg

No

Claritromicina

500 mg

12 horas

Sí, por debajo de 30ml/min

Amoxicilina/clavulanato

875/125 mg1000/125mg

8 horas

Preferiblemente para manejo oral después de ampicilina/sulbactam

Cefuroxima axetil

1000 mg

8 horas

Absorción cercana al 52%

Linezolid

600 mg

12 horas

No

Endovenosos

Ampicilina/sulbactam

1.5-3 g

6 horas

Ceftriaxona

1-2 g

24 horas

No

Cefuroxime

750 mg

8 horas

Uso intravenoso u oral de acuerdo a tolerancia oral del paciente y escenario de atención. Ver dosis oral arriba.

Vancomicina

15 mg/Kg

12 horas

Se recomienda dosis de carga o infusión continua y monitorizar con niveles séricos y función renal. Se puede hacer infusión continua

Si.

Es nefrotóxico

Linezolid

600 mg

12 horas

Medicamento no incluido en el PBS. El linezolid oral sí está incluido.

No

Piperacilina/tazobactam

4.5 g

6 horas

Se puede administrar en infusión continua/extendida.

Cefepime

2 g

8 horas

Se puede administrar en infusión continua/extendida. Riesgo de toxicidad en pacientes con falla renal.

PBS: plan de beneficios en salud.

Fuente: Elaboración propia.

Resumen de la evidencia

Los datos sobre la superioridad o no inferioridad de antimicrobianos en pacientes con NAC que reciben tratamiento ambulatorio son escasos, tal como como lo documenta una revisión Cochrane realizada en 2014.53 Por ejemplo, Maimon et al.,54 en un metanálisis en el que se incluyeron cinco estudios que compararon la utilidad de macrólidos vs. fluoroquinolonas en el tratamiento ambulatorio de la NAC; tres, macrólidos vs. betalactámicos; tres, fluoroquinolonas vs betalactámicos, y dos, cefalosporinas vs. betalactámicos-inhibidores de betalactamasa, no encontraron diferencias significativas en términos de morbilidad o mortalidad, a pesar de que algunos antimicrobianos no cubrían bacterias atípicas.

De forma similar, Bonvehi et al.,55 en un estudio realizado en Argentina en 327 pacientes ambulatorios con NAC y en el que compararon el uso de claritromicina (n=160) vs. amoxicilina+clavulanato (n=167), reportaron que no hubo diferencias significativas entre grupos en las tasas de respuesta clínica y microbiológica, ni tampoco en la presencia de efectos adversos. Por otra parte, estudios que han evaluado la utilidad de la amoxicilina en este escenario clínico han reportado que, comparado con el uso de otros antimicrobianos como las quinolonas de amplio espectro, el uso de altas dosis de este medicamento no ha mostrado ninguna diferencia significativa en términos de éxito clínico y efectos adversos.56,57

La información sobre la frecuencia de los microorganismos causales de la neumonía en Colombia es limitada. En general, se han descrito tres grupos de microorganismos: agentes bacterianos clásicos con un gran potencial de virulencia, entre los que se encuentran S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus; microorganismos intracelulares, usualmente agrupados como atípicos, entre los que se incluyen Mycoplasma pneumoniae, Chlamydiophila pneumoniae, Legionella spp y Coxiella burnetii, y los virus, entre los que destacan en población adulta los virus de la influenza, el virus sincitial respiratorio, los rinovirus, los coronavirus, los adenovirus y, recientemente, el SARS CoV-2. En la Tabla 3 se presenta la información sobre la frecuencia relativa de los microorganismos más frecuentes reportados por estudios colombianos realizados en pacientes con NAC.

La frecuencia de aislamientos de Streptococcus pneumoniae en Colombia, así como la frecuencia relativa de los distintos serotipos y su resistencia a los antimicrobianos en los aislamientos en el país ha variado después de la introducción y uso extenso de las vacunas contra el neumococo en el Programa Ampliado de Inmunización Infantil. Aunque la resistencia a la penicilina disminuyó durante los primeros años posteriores a su inclusión, con la selección de ciertos serotipos no cubiertos por la vacuna, las tasas de resistencia a penicilina, ceftriaxona y macrólidos de los aislamientos de S. pneumoniae han aumentado en los últimos años.58

Además, según datos del Sistema Nacional de Vigilancia en Salud Pública - SIVIGILA, desde 2017 la proporción de aislamientos no sensibles a macrólidos y a penicilinas o ceftriaxona en adultos es mayor al 25% y al 10%, respectivamente.59 Esto implica que se debe mantener la vigilancia epidemiológica de este microorganismo en el país, aunque el impacto de su resistencia a antimicrobianos sigue sin ser claro en el escenario de la neumonía,60 por lo cual se requieren más estudios al respecto.

Pregunta Nº 8. ¿Cuál es la mejor estrategia para el tratamiento antimicrobiano empírico en pacientes adultos hospitalizados con NAC?

Recomendaciones

Pacientes con NAC moderada:

  • Recomendamos usar el siguiente tratamiento antimicrobiano en pacientes adultos hospitalizados con diagnóstico de NAC moderada y sin factores de riesgo para SARM o P. aeruginosa (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: moderada ⨁⨁⨁◯):
    • Monoterapia con un betalactámico (ampicilina/sulbactam) y revalorar 48 a 72 horas después del inicio del tratamiento para considerar la necesidad de adicionar un macrólido (claritromicina) teniendo en cuenta aspectos como el empeoramiento de signos vitales, de la capacidad para comer y del estado mental.

En caso de que el paciente sea alérgico a la penicilina se recomienda utilizar (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: moderada ⨁⨁⨁◯):

  • Monoterapia con ceftriaxona; o
  • Monoterapia con cefuroxima; o
  • Monoterapia con doxiciclina.

Pacientes con NAC grave:

  • Recomendamos usar el siguiente tratamiento antimicrobiano en pacientes adultos hospitalizados con diagnóstico de NAC grave (Tabla 1) y sin factores de riesgo para SARM o P. aeruginosa (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: moderada ⨁⨁⨁◯):
    • Terapia combinada con un betalactámico (ampicilina/sulbactam) y claritromicina.
  • Si el paciente es alérgico a la penicilina, recomendamos utilizar (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: moderada ⨁⨁⨁◯):
    • Terapia combinada con ceftriaxona (en vez de ampicilina/sulbactam) y claritromicina.

Puntos de buena práctica

  • Se debe evitar el uso de quinolonas en el tratamiento de la NAC.
  • No agregar cobertura anaeróbica adicional al esquema terapéutico instaurado por sospecha de neumonía por aspiración, a menos que se sospeche un absceso pulmonar o empiema.

Justificación de la recomendación

Las recomendaciones sobre el tratamiento de pacientes con NAC en el escenario hospitalario se basan en el tratamiento de los microorganismos que más frecuentemente causan la infección. No existe evidencia sólida sobre los beneficios de usar macrólidos o antibióticos para el tratamiento de bacterias atípicas en pacientes hospitalizados con NAC moderada; los estudios que han comparado la monoterapia con betalactámico vs. betalactámico con macrólido no han reportado diferencias significativas en dicho escenario. En el caso de la NAC grave, recomendamos el uso de un macrólido teniendo en cuenta el cubrimiento de bacterias atípicas con alta carga de mortalidad como Legionella y los efectos adicionales de este grupo de medicamentos como la modulación de la inflamación. Además, teniendo en cuenta el perfil de resistencia a quinolonas de los microorganismos causales de NAC y los efectos adversos de estos antibióticos, como punto de buena práctica se debe evitar el uso de este grupo de medicamentos para el tratamiento de estos pacientes. La prescripción de los antimicrobianos debe basarse en el perfil epidemiológico de susceptibilidad a antibióticos de los microorganismos causantes de NAC en cada institución de salud. Ver la Tabla 3 y la Tabla 4.

Resumen de la evidencia

Hay algunos estudios que han comparado el uso de betalactámicos con macrólidos vs monoterapia, aunque esta última con quinolonas, y en los que se ha reportado que no hay diferencias entre ambos regímenes; sin embargo, son estudios de baja calidad, con muestras pequeñas y con un diseño de no inferioridad.61-63 Otras investigaciones han evaluado la no inferioridad de la terapia combinada con betalactámico y macrólido vs. la monoterapia con betalactámico, como el ensayo clínico aleatorizado abierto realizado por Garín et al.64 en 580 pacientes con NAC hospitalizados en 6 hospitales de Suiza y en cual no se documentó una diferencia clara entre los brazos (brazo de monoterapia, n=291 vs. brazo de terapia combinada, n=289), pero sí se sugirió que los pacientes con microrganismos intracelulares se demoraron más tiempo en lograr la estabilidad clínica.

No obstante lo anterior, los resultados reportados por Garín et al.64 difieren de lo descrito por Postma et al.65, quienes, en un ensayo clínico aleatorizado por conglomerados con diseño cruzado realizado en 2283 pacientes con NAC leve a moderada que requirieron hospitalización, compararon varias estrategias de tratamiento para NAC (monoterapia con betalactámicos vs. monoterapia con fluroquinolona vs. terapia combinada con betalactámico y macrólido) y concluyeron que la monoterapia con betalactámico no fue inferior a las demás opciones de tratamiento antimicrobiano para los desenlaces de mortalidad a 90 días y duración de la estancia hospitalaria, siendo esta última similar para todas las estrategias.

Estos datos, en conjunto, sugieren que el beneficio de usar terapia combinada en pacientes hospitalizados con NAC leve o moderada no es claro, ya que su uso no ofrece beneficios en términos de reducción del riesgo de progresión a formas más graves de la enfermedad y de reducción del tiempo de estancia hospitalaria y, en su lugar, sí puede contribuir a un mayor consumo de antibióticos, un mayor gasto de recursos y a un mayor riesgo de efectos adversos. Como alternativa para el tratamiento de pacientes alérgicos a la penicilina, el grupo de consenso recomendó el uso de ceftriaxona, terapia incluida en los estudios de no inferioridad de la monoterapia con betalactámico arriba referenciados. Igualmente, tal como lo señalan las revisiones sistemáticas y meta-análisis de Picard et al.,66 varios estudios clínicos han evidenciado la baja frecuencia de reacciones alérgicas cruzadas en pacientes con antecedente de alergia a la penicilina que reciben este medicamento. La siguiente alternativa en pacientes con antecedente de alergia a los betalactámicos es la doxiciclina, un antibiótico que ha demostrado ser eficiente por su amplio cubrimiento de los microorganismos causales, así como seguro y costo-efectivo para el tratamiento de pacientes con NAC leve a moderada en el escenario hospitalario.67

En pacientes con NAC grave recomendamos el uso de betalactámico más macrólido para asegurar el cubrimiento de bacterias atípicas como Legionella, cuya presencia se ha relacionado con una mayor tasa de mortalidad, especialmente en adultos mayores. Al respecto, Nie et al.,68 en un metaanálisis que incluyó 16 estudios de cohorte (42 942 pacientes con NAC), reportaron una disminución significativa en la mortalidad en los pacientes que recibieron la terapia dual (betalactámico+macrolido) en comparación con los que recibieron monoterapia (betalactámico) (OR ajustado: 0.67, IC95%: 0.61-0.73; p<0.01).

Un hallazgo similar también fue descrito en la revisión sistemática y meta-análisis (14 estudios; 33 618 pacientes) realizada por Horita et al.,69 específicamente en pacientes con NAC grave, donde el modelo aleatorio del meta-análisis arrojó un OR para todas las causas de mortalidad de betalactámico con macrólido comparado con monoterapia con betalactámico de 0.80 (IC95%: 0.69-0.92; p<0.01). En conjunto, esta evidencia sugiere el beneficio de usar terapia combinada en pacientes con NAC grave, lo cual está relacionado, ya sea con el cubrimiento antibiótico de especies de Legionella que pueden estar asociadas con una mayor mortalidad, o con el efecto de la terapia combinada en pacientes con NAC grave causa por S. pneumoniae.68

Pregunta Nº 9. ¿Cuál es la mejor estrategia para el tratamiento antimicrobiano empírico en pacientes adultos hospitalizados con NAC y con factores de riesgo de SARM o P. aeruginosa?

Recomendaciones

  • Recomendamos realizar las siguientes acciones en pacientes adultos hospitalizados con diagnóstico de NAC moderada o grave y con aislamiento respiratorio previo de SARM (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: baja ⨁⨁◯◯):
    • Iniciar terapia antimicrobiana según el reporte microbiológico del aislamiento respiratorio previo Y
    • Realizar cultivo o PCR de muestra respiratoria del tracto superior para, con base en los resultados, ajustar el tratamiento o confirmar la necesidad de continuar la terapia O
    • Realizar cultivo o PCR de muestra respiratoria del tracto superior para, con base en los resultados, ajustar e tratamiento o confirmar la necesidad de continuar la terapia E iniciar terapia antimicrobiana con vancomicina o linezolid.
  • Recomendamos realizar las siguientes acciones en pacientes adultos hospitalizados con diagnóstico de NAC moderada o grave y con aislamiento respiratorio previo de P. aeruginosa (fuerza de la recomendación: fuerte a favor; calidad de la evidencia de baja: ⨁⨁◯◯):
    • Iniciar terapia antimicrobiana según el reporte microbiológico de aislamiento respiratorio previo Y
    • Realizar cultivo o PCR de muestra respiratoria del tracto superior para, con base en los resultados, ajustar el tratamiento o confirmar la necesidad de continuar la terapia O
    • Realizar cultivo o PCR de muestra respiratoria del tracto superior para, con base en los resultados, ajustar el tratamiento o confirmar la necesidad de continuar la terapia E iniciar terapia antimicrobiana con piperacilina/tazobactam o cefepime.
  • Sugerimos realizar las siguientes acciones en pacientes adultos hospitalizados con diagnóstico de NAC moderada y con antecedente de hospitalización y/o terapia antimicrobiana en los últimos 90 días o con factores de riesgo validados localmente para SARM o P. aeruginosa (fuerza de la recomendación: débil a favor; calidad de la evidencia: baja ⨁⨁◯◯):
    • Realizar cultivo o PCR de muestra respiratoria del tracto superior E
    • Iniciar tratamiento antibiótico que cubra SARM o P. aeruginosa solo si los resultados son positivos.
  • Recomendamos realizar las siguientes acciones en pacientes adultos hospitalizados con diagnóstico de NAC grave y con antecedente de hospitalización y/o terapia antimicrobiana en los últimos 90 días o con factores de riesgo validados localmente para SARM (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: baja ⨁⨁◯◯):
    • Realizar cultivo o PCR de muestra respiratoria del tracto superior para, con base en los resultados, ajustar el tratamiento o confirmar la necesidad de continuar la terapia E iniciar terapia antimicrobiana con vancomicina o linezolid, junto con medición de los niveles de vancomicina, en caso de utilizarse.
  • Recomendamos realizar las siguientes acciones en pacientes adultos hospitalizados con diagnóstico de NAC grave y con antecedente de hospitalización y/o terapia antimicrobiana en los últimos 90 días o con factores de riesgo validados localmente para P. aeruginosa (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: baja ⨁⨁◯◯):
    • Realizar cultivo o PCR de muestra respiratoria del tracto superior para, con base en los resultados, ajustar el tratamiento o confirmar la necesidad de continuar la terapia E iniciar terapia antimicrobiana con piperacilina/tazobactam o cefepime.

Justificación de la recomendación

No existen estudios clínicos sobre factores predictores de infección por SARM o P aeruginosa y tampoco escalas de predicción que permitan determinar su presencia; esto, sumado al hecho de que la prevalencia de estos microrganismos varía ampliamente en cada región e institución de salud del país, llevó al grupo de consenso a recomendar el uso de antimicrobianos que cubren SARM o P. aeruginosa en pacientes con NAC moderada a grave y con antecedente de aislamiento de estos microrganismos y a realizar cultivo o PCR de muestra respiratoria del tracto superior para instaurar un tratamiento dirigido que promueva el uso racional de antimicrobianos.

El otro escenario clínico donde recomendamos el tratamiento antibiótico de estas bacterias es en pacientes con NAC grave y antecedente de hospitalización y/o terapia antimicrobiana en los últimos 90 días o con factores de riesgo validados localmente para la presencia de SARM o P. aeruginosa; la fuerza de esta recomendación es débil y la evidencia es de baja calidad porque no se encontraron estudios que respaldaran el aumento del riesgo de infección por SARM o P. aeruginosa en presencia de estos factores; sin embargo, debido a la alta mortalidad de los pacientes con NAC grave se debe considerar el uso de antibióticos que cubran estas bacterias en este escenario clínico.

Resumen de la evidencia

El principal factor de riesgo para sospechar la infección por P. aeruginosa o SARM es el antecedente de infección o colonización por alguno de estos microorganismos; en este sentido, por ejemplo, para el caso de SARM se ha descrito un OR de 6.21 (IC95%: 3.25-11.85).70 Otros factores de riesgo incluyen la presencia de comorbilidad pulmonar (OR: 5.8, IC95%: 2.2-15.3; p<0.01), tener antecedente de hospitalización (OR: 3.8, IC95%: 1.8-8.3; p=0.02),71 especialmente en los últimos 90 días, y el uso de antimicrobianos en los últimos 90 días  (OR: 2.90, IC95%: 1.13-7.45; p=0.02).72 Otro factor de riesgo que debe ser considerado para iniciar el cubrimiento antibiótico es la epidemiología de estas infecciones en la institución de salud, la cual debe incluir el perfil de susceptibilidad antimicrobiana local.

En pacientes con NAC moderada o severa y en los que, según la presencia de factores de riesgo, se sospeche infección por SARM o P. aeruginosa se deben realizar cultivos o PCR de muestra respiratoria para confirmar esta etiología y ajustar el tratamiento antimicrobiano, porque el escalonamiento de los antimicrobianos sí es pertinente, ya que se ha demostrado que es seguro y que reduce la duración del tratamiento antibiótico, la duración de la estancia hospitalaria y la frecuencia de complicaciones relacionadas con los efectos adversos de los antimicrobianos de amplio espectro.73

Al respecto, Cremers et al.74 encontraron que, en comparación con no realizar ningún ajuste, ajustar la terapia antibiótica redujo la mortalidad en pacientes con NAC nemocócica bacteriémica (OR ajustado: 0.35, IC95%: 0.12-0.99). Además, Carugati et al.,75 en un estudio realizado con datos de 261 pacientes hospitalizados con CAP bateriémica, reportaron que el ajuste de la terapia antimicrobiana (desescalamiento) según los resultados de las pruebas microbiológicas no aumentó el riesgo de fracaso clínico en comparación con los pacientes en los que no se desescaló la terapia antibiótica (RR: 0.89, IC95%: 0.63-1.27, p=0.54). No obstante lo anterior, en un reciente estudio de cohorte de gran magnitud (88 605 hospitalizaciones por NAC en centros médicos del Veterans Affairs health care system), el análisis con ponderación inversa de los pesos mostró que el uso empírico de linezolid o vancomicina en estos pacientes no disminuyó la mortalidad, sino que, por el contrario, la aumentó.76

Los costos de los antimicrobianos genéricos en Colombia son bastante bajos y es posible que los esquemas terapéuticos recomendados no sean costosos, tanto para la terapia endovenosa como para la terapia oral. Sin embargo, como se mencionó arriba, disponer de evaluaciones formales de la costo-efectividad de los tratamientos recomendados es una necesidad de investigación en la región.

Pregunta Nº 10. ¿Cuál es la duración apropiada del tratamiento antimicrobiano en pacientes adultos con NAC, tanto ambulatorios, como hospitalizados?

Recomendaciones

  • Pacientes con NAC leve a moderada:

Recomendamos que la terapia antimicrobiana dure máximo 5 días en total, así como tener en cuenta los siguientes criterios para suspenderla: la estabilidad clínica del paciente (la resolución de alteraciones de los signos vitales [frecuencia cardíaca, frecuencia respiratoria, presión arterial, saturación de oxígeno y temperatura corporal]), la adecuada tolerancia a la administración oral de alimentos y líquidos y la ausencia de alteración del estado mental (fuerza de la recomendación: fuerte; calidad de la evidencia: moderada ⨁⨁⨁◯).

  • Pacientes con NAC grave:

Recomendamos establecer la duración de la terapia antimicrobiana según la evolución clínica del paciente, los resultados de pruebas microbiológicas y los niveles de biomarcadores (fuerza de la recomendación fuerte; calidad de la evidencia: moderada ⨁⨁⨁◯).

Punto de buena práctica

Si está disponible, se puede utilizar la prueba de PCT sérica para decidir la suspensión de la terapia antimicrobiana en pacientes hospitalizados.

Justificación de la recomendación

Teniendo en cuenta que, en general, la adecuada prescripción de antimicrobianos lleva a la estabilidad clínica de los pacientes una vez pasadas 48-72 horas desde el inicio del tratamiento, recomendamos que la terapia antibiótica dure máximo 5 días en pacientes con NAC leve a moderada y que la suspensión se decida con base en el juicio clínico, el cual incluye criterios como la ausencia de alteraciones en signos vitales, la adecuada tolerancia a la administración oral de alimentos y líquidos, el estado de conciencia y la ausencia de complicaciones. En casos de NAC grave, la duración del tratamiento antimicrobiano debe establecerse según el criterio médico, teniendo en cuenta factores clínicos, microbiológicos y el seguimiento de biomarcadores como la PCT sérica si es posible.

Resumen de la evidencia

Tradicionalmente, los estudios sobre la duración del tratamiento antimicrobiano en pacientes con NAC se han agrupado en dos clases: una duración <7 días y una duración ≥a 7 días. Los trabajos identificados, como el realizado por el Moussaoui et al.77 en 119 pacientes con NAC, comparan el uso de amoxicilina, inicialmente intravenosa por 3 días y luego oral por 5 días más, con el uso de placebo en pacientes con NAC leve a moderada, concluyendo que aunque ambas estrategias mostraron resultados similares en los desenlaces de resolución de síntomas y cambios en la radiografía, la frecuencia de efectos adversos fue mayor en el grupo de pacientes en el que el antibiótico fue administrado 7 o más días (21% vs. 11%).

Estos resultados han sido confirmados por otras investigaciones como la realizada por Dunbar et al.78 en 528 pacientes con NAC leve a moderada y en la que no hubo diferencias estadísticamente significativas en las tasas de respuesta clínica, ni en las tasas de erradicación microbiológica entre el uso de levofloxacina por 5 días vs. el uso de este medicamento por 10 días. De igual forma, además de no encontrar hallazgos discordantes entre la duración de un tratamiento antibiótico (7 días vs. 10 días) en pacientes hospitalizados con NAC grave en cuanto a recurrencias tardías o tasas de curación, Siegel et al.79 reportaron una menor duración de la estancia hospitalaria, una menor frecuencia de efectos adversos y una reducción en los costos en el grupo de pacientes que recibieron el régimen de tratamiento antibiótico de menor duración.

Es importante mencionar que también se ha sugerido el uso de escalas para evaluar la posibilidad de implementar tratamientos antimicrobianos de incluso 3 días, pues estos scores, algunas de las cuales han sido traducidas y adaptadas culturalmente al español,80 tienen en cuenta los síntomas y la evolución clínica subjetiva del paciente para definir el tiempo de tratamiento.

La suspensión del tratamiento antimicrobiano debe basarse en la estabilidad clínica del paciente, entendida como la presencia de signos vitales normales, la adecuada tolerancia a la administración oral de alimentos y líquidos y la ausencia de alteración del estado mental; en este sentido, se espera observar estos hallazgos en pacientes con NAC leve a moderada 2 o 3 días después de haberse iniciado la administración de los antimicrobianos.81,82 Además, la evaluación de la condición clínica de los pacientes ha demostrado reducir el tiempo de hospitalización y el tiempo de uso de antimicrobianos, sin que esto tenga un impacto adverso en la seguridad de los pacientes.83

Finalmente, es importante mencionar que actualmente no se dispone de una evaluación de la costo-efectividad de las intervenciones propuestas, aunque se espera que estas sean costo-efectivas, teniendo en cuenta que tienen el potencial de reducir la duración de la estancia hospitalaria y, por tanto, las posibles complicaciones asociadas, lo que implicaría una reducción en los costos asociados con la atención de estos pacientes, ya que su uso permitiría un egreso hospitalario temprano.

Pregunta Nº 11. ¿Cuál es la vía de administración adecuada del tratamiento antimicrobiano en pacientes adultos con NAC moderada a grave?

Recomendaciones

  • Recomendamos usar antimicrobianos orales como tratamiento de primera línea en pacientes adultos con NAC moderada a grave, siempre teniendo en cuenta la tolerancia a la administración oral de alimentos/medicamentos/líquidos y la gravedad de la infección (fuerza de la recomendación fuerte; calidad de la evidencia: muy baja ⨁◯◯◯).
  • Recomendamos revalorar la condición clínica del paciente 48 horas después de haberse iniciado la terapia antimicrobiana intravenosa para considerar la posibilidad de cambiar a antimicrobianos orales (fuerza de la recomendación fuerte; calidad de la evidencia: muy baja ⨁◯◯◯).

Justificación de la recomendación

Inicialmente, la vía de administración de los antimicrobianos en pacientes con NAC moderada a grave fue exclusivamente intravenosa durante todo el tratamiento; sin embargo, estudios más recientes han promovido el uso de antimicrobianos orales teniendo en cuenta la disminución de efectos adversos, las facilidades que ofrece esta vía de administración y la efectividad del tratamiento antimicrobiano oral, en particular en los casos que ya se han completado 48 horas de terapia intravenosa y el paciente esté clínicamente estable, por lo que el grupo de consenso aceptó e incluyó esta recomendación que incentiva el uso racional de antimicrobianos, reduce los costos de atención y el tiempo de hospitalización y, según la evidencia identificada, es una decisión segura.

Resumen de la evidencia

La evidencia identificada sobre la ruta de administración de antimicrobianos en pacientes con NAC moderada a grave es de muy baja calidad. Por ejemplo, en una revisión de la literatura, Cassiere & Fein84 informan que el cambio de la administración intravenosa a la administración oral en pacientes de bajo riesgo fue una intervención efectiva y segura en el tratamiento de la NAC. Igualmente, Marras et al.,85 en un meta-análisis que incluyó 7 estudios (1 366 pacientes adultos hospitalizados con NAC en total), concluyeron que en los pacientes con NAC no grave que recibieron tratamiento antibiótico oral, la estrategia fue efectiva y la terapia duró 1.3 días menos (IC95%: 0.4%-2.2% días; p<0.01) que en el grupo de pacientes que recibieron terapia intravenosa.

Además, según la evidencia encontrada, los principales costos del tratamiento de la NAC moderada a grave son la duración de la terapia antimicrobiana intravenosa y la duración de la estancia hospitalaria, por lo que el cambio a antibióticos orales reduce de manera significativa los costos de atención de estos pacientes, sin que este cambio implique perjuicios para el paciente o se asocie con recurrencias de la infección y el desarrollo de complicaciones.86 Una vez el paciente esté clínicamente estable y se haya realizado el cambio de antibióticos intravenosos a orales, no se requiere observación intrahospitalaria, por lo que el egreso, si no hay otras contraindicaciones, puede ser inmediato, como lo confirmaron Nathan et al.87 en su estudio retrospectivo realizado con datos obtenidos del US Medicare National Pneumonia Project. En Colombia, los antimicrobianos mencionados en las recomendaciones están incluidos en el PBS del sistema de salud colombiano.

Pregunta Nº 12. ¿Se debe incluir terapia antiviral en el tratamiento de pacientes adultos con NAC que dan positivo en la prueba de influenza?

Recomendaciones

  • Recomendamos iniciar un tratamiento para la influenza (p. ej., oseltamivir) en pacientes adultos con NAC grave que den positivo en la prueba de influenza, independientemente de la duración de la enfermedad antes del diagnóstico (fuerza de la recomendación: fuerte a favor; calidad de la evidencia: muy baja⨁◯◯◯).

Justificación de la recomendación

La evidencia sobre el uso de tratamiento antiviral de la influenza en el escenario de la NAC es muy escasa y de muy baja calidad; no encontramos ningún ensayo clínico que evaluara directamente la utilidad de este tipo de tratamiento exclusivamente en pacientes con diagnóstico de NAC, sino que la evidencia proviene de estudios observacionales realizados en pacientes con diferentes tipos de infecciones respiratorias del tracto respiratorio inferior y en los que se ha descrito un beneficio en la reducción de la frecuencia de complicaciones, de la duración de los síntomas y del riesgo de mortalidad, incluso cuando la administración del antiviral se inicia después de 48 horas del inicio de los síntomas; sin embargo, estos resultados no han sido consistentes y solo se han reportado para el caso de pacientes con NAC severa. Además, los beneficios de usar estos medicamentos solo han sido descritos en pacientes con prueba microbiológica positiva para virus de la influenza, por lo que el grupo de consenso decidió realizar esta recomendación solo en este escenario.

Resumen de la evidencia

No encontramos ensayos clínicos que evaluaran el uso de oseltamivir en pacientes con NAC; de hecho, los estudios identificados son muy pocos y tienen una muy baja calidad con un alto riesgo de sesgos. Por ejemplo, Lee et al.88 informaron que en pacientes hospitalizados con infección respiratoria confirmada por influenza A/B (n=754), el uso del antiviral se asoció significativamente con una reducción del riesgo de mortalidad (HR ajustado: 0.27, IC95%: 0.13-0.55; p<0.01) y que el tratamiento temprano (dentro de los 2 días posteriores al inicio de síntomas) se asoció con una descontinuación más rápida de la terapia con oxígeno (HR ajustado: 1.30, IC95%: 1.01-1.69; p=0.04) y con un alta hospitalaria más temprana (HR ajustado: 1.28, IC95%: 1.04-1.57; p=0.01). McGeer et al.,89 en un estudio realizado en Toronto en 512 pacientes hospitalizados con diagnóstico de influenza confirmado por laboratorio (185 niños, de los cuales ninguno murió), reportaron que el tratamiento con medicamentos antivirales contra la influenza se asoció con una disminución significativa en la mortalidad (OR: 0.21, IC95%: 0.06-0.80), pero que no se observaron beneficios en otros desenlaces como la duración de la estancia hospitalaria.

En algunos de los estudios clínicos iniciales sobre este tema, como el realizado en Estados Unidos por Siston et al.90 con datos de 788 mujeres embarazadas diagnosticadas con influenza AH1N1, se estableció que el tratamiento antiviral debía iniciar antes de que pasaran 48 horas desde el inicio de los síntomas,90 sin embargo también se han descrito buenos resultados cuando el uso de esta terapia comienza 4 a 5 días después del inicio de los síntomas.91

Aunque la utilidad del tratamiento antiviral se ha reportado principalmente en el escenario intrahospitalario, en el ambiente ambulatorio también se ha mostrado una reducción en el riesgo de complicaciones, como lo evidencia una revisión sistemática y meta-análisis que incluyó 9 ensayos clínicos (4 328 pacientes) y en donde se reportó que la frecuencia de complicaciones del tracto respiratorio inferior con requerimiento de antibióticos a las 48 horas fue más baja en el grupo que recibió oseltamivir en comparación con el grupo placebo (4.2% vs. 8.7%), estimando una reducción del 44% del riesgo de estas complicaciones con el tratamiento con este antiviral (RR: 0·56, 95%CI:0.42-0.75; p=00001), con una diferencia absoluta de riesgo de -3·8% (95%CI: -5.0 a -2.2).92 En el caso del escenario intrahospitalario, Muthuri et al.,93 en una revisión sistemática que incluyó datos individuales de 29 234 pacientes infectados por el virus de la influenza H1N1pdm09 y que hospitalizados durante la pandemia de 2009, encontraron que, en comparación con no usar ninguna terapia antiviral, el tratamiento con inhibidores de la neuraminidasa (independientemente del momento de inicio) se asoció con una reducción en el riesgo de mortalidad (OR ajustado: 0.81, IC95%: 0.70-0.93; p=0.0024) y que, además, comparado con el inicio tardío, el inicio temprano del tratamiento (dentro de los 2 primeros días posteriores al inicio de los síntomas) también se asoció significativamente con una reducción en el riesgo de mortalidad (adjusted OR: 0·50, IC95%: 0·37-0·67; p<0.0001).

El uso de oseltamivir y de zanamivir (otro inhibidor de la neuroaminidasa) para el tratamiento de la influenza ha sido estudiado ampliamente en el escenario ambulatorio; al respecto, se ha reportado que si bien estos antivirales reducen los síntomas de forma leve, su uso no tiene una repercusión clínica relevante y su impacto en la disminución del uso de antibióticos es bajo o nulo.94 Adicionalmente, una revisión sistemática que incluyó ensayos clínicos controlados aleatorizados realizados en pacientes con exposición confirmada o sospechada a virus de la influenza reportó que, en adultos, si bien el uso de oseltamivir redujo el tiempo en el que se produjo el primer alivio de los síntomas en 16.8 horas (IC95%: 8.4-25.1 horas; p<0.001), este medicamento se asoció con un aumento en la frecuencia de náuseas, vómito y síntomas psiquiátricos,95 concluyendo así que su uso en el escenario ambulatorio no es muy beneficioso para estos pacientes. Teniendo en cuenta lo anterior, se enfatiza la necesidad de usar este medicamento solo en pacientes con un diagnóstico de influenza confirmado microbiológicamente.

En Colombia, durante la pandemia de Influenza H1N1 de 2009 se implementó el uso de oseltamivir para el tratamiento de los pacientes con infección respiratoria aguda grave, por lo que el acceso a este medicamento ha sido garantizado desde entonces en todas las instituciones de salud del país, lo que hace que esta recomendación sea factible y que tenga un impacto limitado en los costos asociados con la atención de estos pacientes en los que actualmente incurren las instituciones de salud.96

Pregunta Nº 13. ¿Se deben usar corticosteroides en pacientes adultos hospitalizados con NAC?

Recomendaciones

  • Pacientes con NAC leve a moderada:

No recomendamos usar corticosteroides en el tratamiento de pacientes con NAC leve a moderada (fuerza de la recomendación: fuerte en contra; calidad de la evidencia: moderada ⨁⨁⨁◯).

  • Pacientes con NAC grave (Tabla 1):

Sugerimos usar corticosteroides en pacientes con NAC grave (fuerza de la recomendación: débil a favor; calidad de la evidencia: moderada ⨁⨁⨁◯).

Puntos de buena práctica

  • Siempre que no haya contraindicaciones, usar corticosteroides en pacientes con COVID-19.
  • Evitar el uso de corticosteroides en pacientes con influenza.

Justificación de la recomendación

No encontramos estudios que soporten el uso de corticosteroides en pacientes con NAC leve a moderada; sin embargo, existe evidencia científica del beneficio de su uso en pacientes con NAC grave en términos de mortalidad, requerimiento de ventilación mecánica y duración de la estancia en UCI. Por lo tanto, sugerimos usar estos medicamentos en estos pacientes teniendo en cuenta el juicio clínico, la ausencia de contraindicaciones y el análisis del balance entre los riesgos y beneficios, pues su uso se asocia con frecuencia con efectos adversos, siendo la hiperglicemia el más común, lo que podría afectar el desenlace clínico en pacientes con sepsis de origen pulmonar. Los corticosteroides y las dosis sugeridas a usar en estos pacientes se presentan en la Tabla 5.97,98

Tabla 5. Corticosteroides de uso clínico sugeridos en el manejo de pacientes con NAC grave.

Glucocorticoides

Dosis equivalente aproximada (mg)

Actividad glucocorticoide relativa

Actividad mineralocorticoide relativa

Duración de la acción (horas)

Acción corta

Hidrocortisona

20

1

1

8-12

Cortisona

25

0.8

0.8

8-12

Acción intermedia

Prednisona

5

4

0.8

12-36

Prenisolona

5

4

0.8

12-36

Metilprednisolona

4

5

0.5

12-36

Triamcinolona

4

5

0

12-36

Acción larga

Dexametasona

0.75

30

0

36-76

Betametasona

0.6

30

0

36-76

Mineralocorticoide

Fludrocortisona

0

15

150

24-36

Elaboración con base en Samuel et.al.97 y Liu et al.98

Resumen de la evidencia

Hay algunos estudios que han documentado el beneficio de usar corticosteroides en pacientes con NAC grave. Confalioniere et al.,99 en un ensayo controlado aleatorio multicéntrico realizado en 46 pacientes con NAC admitidos a la UCI y que recibieron tratamiento antibiótico, encontraron que, comparado con el placebo, el uso de hidrocortisona en infusión se relacionó con una disminución considerable de la estancia hospitalaria y de la mortalidad; sin embargo, no ha sido posible reproducir esta considerable reducción en el riesgo de muerte de estos pacientes en otras investigaciones e incluso algunas, como el ensayo doble ciego controlado aleatorizado multicéntrico realizado por Torres et al.100 en 120 pacientes con NAC grave, han descrito que el uso de corticosteroides no llevó a una disminución de la estancia hospitalaria, ni de la mortalidad.

Inicialmente, diferentes meta-análisis, como el realizado en 2015 por Chen et al.101 (7 ensayos clínicos aleatorizados; 944 pacientes con NAC), documentaron que el uso de estos medicamentos (específicamente glucocorticoides) se asoció con una disminución en la estancia hospitalaria, mientras que meta-análisis más recientes, como el realizado por Jian et al.102 (10 ensayos clínicos aleatorizados; 665 pacientes), han identificado una reducción importante en la mortalidad. Además, otros estudios, como el ensayo doble ciego controlado aleatorizado multicéntrico realizado por Blum et al.103 en 785 pacientes adultos con NAC hospitalizados, han documentado que el tiempo para alcanzar la estabilidad clínica es menor en pacientes que reciben esteroides como la prednisona y que el uso de estos medicamentos también se asocia con una reducción en el tiempo de requerimiento de ventilación mecánica.

El uso de esteroides se ha asociado con efectos adversos importantes como alteraciones en el metabolismo de la glucosa (hiperglicemia) y sangrado gastrointestinal. Sin embargo, en los estudios clínicos identificados, y a las dosis y tiempos recomendados en esta GPC, no se reportó un incremento en la frecuencia de estos eventos.102 En todo caso, en el caso de pacientes con sepsis pulmonar se debe evaluar la presencia de efectos adversos de forma rutinaria y tomar las medidas adecuadas para su prevención y control oportuno.

Por otra parte, el uso de esteroides es una práctica estándar en el manejo de pacientes con COVID-19, por lo que, siempre que no haya una contraindicación, estos medicamentos deben usarse en estos pacientes.9

Por último, según un meta-análisis publicado recientemente y que incluyó 21 estudios observacionales, el uso de corticosteroides se asoció con un aumento en la mortalidad en pacientes con influenza (OR: 3.9, IC95%: 2.3-6.6; 15 estudios; HR ajustado: 1.49, IC95%: 1.09-2.02; 6 estudios).104

Implementación y actualización de la GPC

Proponemos que esta GPC sea implementada en las instituciones de salud del país que presten servicios de atención en salud a pacientes adultos con NAC con el fin de apoyar las actividades relacionadas con el tratamiento de esta población y los programas de optimización del uso de antimicrobianos. De igual forma, proponemos usar los indicadores que se presentan en la Tabla 6 para medir la gestión de la implementación de la guía, con la frecuencia y obligatoriedad de reporte que cada institución considere pertinente.

Tabla 6. Indicadores para la medición de la implementación de la guía de práctica clínica.

Indicador

Numerador

Denominador

Interpretación

Proporción de pacientes con tinción de Gram y cultivo de esputo

Número de pacientes con NAC grave en los que se realizó tinción de Gram y cultivo de esputo

Número total de pacientes con NAC grave

Este indicador identifica el uso de la tinción de Gram y el cultivo de esputo en pacientes con NAC grave

Proporción de pacientes con hemocultivos

Número de pacientes con NAC grave en los que se realizó hemocultivo

Número total de pacientes con NAC grave

Este indicador identifica el uso del hemocultivo en pacientes con NAC grave

Proporción de pacientes con prueba de influenza

Número de pacientes con NAC grave o con comorbilidad en los que se realizó prueba de influenza

Número de pacientes con NAC grave o con comorbilidad

Este indicador identifica el uso de la prueba para detectar de los virus de la influenza en pacientes de alto riesgo con NAC

Uso de reglas de predicción clínica

Número de pacientes con NAC que requieren manejo intrahospitalario y en los que se usó una regla de predicción clínica al ingreso

Número total de pacientes con NAC admitidos a hospitalización

Este indicador identifica el uso de reglas de predicción clínica en pacientes con NAC admitidos a hospitalización

Tratamiento antimicrobiano ambulatorio

Número de pacientes con NAC de manejo ambulatorio con indicación de tratamiento con amoxicilina

Número total de paciente con NAC de manejo ambulatorio

Este indicador identifica el uso apropiado de antibióticos en pacientes con NAC de manejo ambulatorio

Tratamiento hospitalario con monoterapia

Número de pacientes con NAC leve o moderada hospitalizados en sala general que reciben monoterapia con ampicilina/sulbactam como tratamiento inicial

Número total de pacientes con NAC leve o moderada hospitalizados en sala general

Este indicador identifica el uso apropiado de antibióticos en pacientes con NAC leve o moderada hospitalizados

Tratamiento hospitalario con terapia combinada

Número de pacientes con NAC grave que reciben terapia combinada

Número total de pacientes con NAC grave admitidos a la UCI

Este indicador identifica el uso apropiado de antibióticos en pacientes con NAC grave admitidos a la UCI

Duración de la terapia ambulatoria

Número de pacientes con NAC leve de manejo ambulatorio y con indicación de tratamiento antibiótico por 5 días o menos

Número total de pacientes con NAC

de manejo ambulatorio

Este indicador identifica la duración apropiada de la terapia antibiótica en pacientes con NAC que únicamente requieren tratamiento ambulatorio

Duración de la terapia hospitalaria

Número de pacientes con NAC leve o moderada hospitalizados que reciben tratamiento antibiótico por 5 días o menos

Número total de pacientes con NAC

de manejo ambulatorio

Este indicador identifica la duración apropiada del tratamiento antibiótico en pacientes con NAC leve o moderada hospitalizados en sala general

Terapia antimicrobiana vía oral

Número de pacientes con NAC leve o moderada hospitalizados en sala general que reciben tratamiento antibiótico oral como estrategia inicial de manejo

Número total de pacientes con NAC leve o moderada hospitalizados en sala general que toleran la administración oral de antibióticos

Este indicador identifica la frecuencia de uso de terapia antibiótica oral en pacientes con NAC leve o moderada hospitalizados en sala general

Cambio de antibióticos intravenosos a orales

Número de pacientes con NAC hospitalizados en sala general y en los que, luego de revaloración a las 48 horas de inicio de la terapia antimicrobiana intravenosa, se realizó cambio a terapia antibiótica oral

Número total de pacientes con NAC hospitalizados en sala general que inicialmente recibieron terapia antibiótica intravenosa y que toleran la administración oral de antibióticos

Este indicador identifica la frecuencia del cambio oportuno de la terapia antibiótica intravenosa a la terapia oral en pacientes con NAC hospitalizados en sala general

Uso de antivirales

Número de pacientes con prueba de influenza positiva en los que se instaura tratamiento con oseltamivir

Número total de pacientes con NAC con prueba positiva de influenza

Este indicador identifica el uso de antivirales en pacientes con NAC grave

Uso de esteroides

Número de pacientes con NAC grave en los que se instaura tratamiento con esteroides

Número total de pacientes con NAC grave

Este indicador identifica el uso de esteroides en pacientes con NAC grave

Fuente: Elaboración propia

Con el objetivo de facilitar la implementación de la presente GPC, se emplearan las siguientes herramientas de difusión que permitirán a los profesionales de la salud del país tener un mejor acceso a sus contenidos: la publicación de la guía en la Revista de la Facultad de Medicina de la Universidad Nacional de Colombia y en la página web de la Asociación Colombiana de Infectología y la inclusión de las recomendaciones de la guía como parte de los contenidos de un curso abierto masivo en línea (MOOC, por su sigla en inglés) y una aplicación móvil sobre el manejo de la NAC.

Por último, consideramos que la presente GPC debe actualizarse en un plazo no mayor a 5 años, siguiendo la misma metodología y rigurosidad que se empleó para su desarrollo. Los temas a abordar podrán ser replanteados según la necesidad de la práctica clínica o la aparición de nueva evidencia que deba ser incluida en la GPC.

Conflicto de interéses

Los siguientes autores declararon no tener conflicto de intereses: SIC, EAS, DPF, LCNB, CHS, EPV, FEM, WC, JACG, SDM, CJE, IJG, SLC, JAD, NG, JEM, MP. Los siguientes autores declararon tener conflicto de intereses: JACL (Pfizer, Novo Nordisk), AS (Johnson & Johnson), JVT (Boehringer Ingelheim, GlaxoSmithKline), MCV (Pfizer), CAA (Merck Sharp & Dohme, Pfizer), ALL (Merck Sharp & Dohme, Pfizer), JEP (Procaps, GPC Pharma), IAR (Pfizer), FOG (Merck Sharp & Dohme, Pfizer, Fresenius Kabi), TE (Novo Nordisk), FG (Procaps).

Financiación

Este documento fue elaborado en el marco del proyecto “Programas de administración de antimicrobianos en un país latinoamericano” de la Universidad Nacional de Colombia, el cual dentro de sus objetivos contempló la elaboración de una GPC para el manejo de la NAC en el contexto colombiano. Proyecto financiado por un Grant de la Sociedad Internacional de Enfermedades Infecciosas - ISID y Pfizer.

Agradecimientos

Representantes de los pacientes: José Ernesto Mosquera y Mildred Pérez, Asociación de Usuarios de Méderi.

Apoyo administrativo: Fabiam Andrés Ariza, Facultad de Medicina, Universidad Nacional de Colombia.

Independencia editorial

El contenido de la presente guía fue desarrollado de manera libre; no hubo ninguna influencia por parte de la ISID y/o de Pfizer. Todos los pasos considerados en la metodología para el desarrollo de la presente guía, desde la conformación del GDG, hasta la elaboración de las recomendaciones y redacción del documento final, fueron realizados en su totalidad y de forma independiente por el grupo desarrollador. Los entes patrocinadores no participaron en dicho proceso, ni tuvieron injerencia sobre el contenido del presente documento.

Referencias

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104.Lansbury LE, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Shen Lim W. Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis. Crit Care Med. 2020;48(2):e98-e106. https://doi.org/gjvmq7.

Material suplementario

Tabla suplementaria 1: Estrategia de búsqueda en Medline.

1

exp community-acquired infections/

2

(community-acquired adj2 infection$).mp.

3

(community-acquired adj2 pneumonia).mp.

4

exp respiratory tract infections/.

5

(respiratory adj2 tract adj2 infection$).mp.

6

or/1-5

7

exp coronavirus/

8

exp coronavirus infections/

9

(corona$ adj2 infection$).mp.

10

((corona* or corono*) adj2 (virus* or viral* or virinae*)).ti,ab,kw.

11

or/7-10

12

6 not 11

13

exp practice guidelines as topic/

14

exp practice guideline/

15

(practice adj2 guide$).mp.

16

or/13-15

17

12 and 16

18

exp randomized controlled trials as topic/

19

exp randomized controlled trial/

20

exp Cohort Studies/

21

or/18-20

22

17 not 21

23

limit 22 to yr=”2015 -Current”

Recibido: 22 de febrero de 2021; Aceptado: 11 de noviembre de 2021

Abstract

Pneumonia continues to be one of the main causes of consultation and hospitalization. Besides having a high impact in terms of morbidity and mortality, it is further aggravated by the current problem of antimicrobial resistance. Thus, establishing guidelines that allow adequate diagnosis and treatment is of great importance to obtain better clinical outcomes and promote a rational use of antibiotics in these patients. This clinical practice guideline (CPG) contains evidence-based recommendations for the diagnosis and treatment of community-acquired pneumonia in the adult population, which were developed by means of an evidence-based CPG adaptation process for the Colombian context.

Keywords:

Clinical guidelines as Topic, Pneumonia, Respiratory tract infections, Community-Acquired Infections, Colombia (MeSH).

Introduction

Pneumonia is an infection that can affect one or both lungs and presents with symptoms ranging from mild to severe, including cough (with or without mucus), fever, chills, and shortness of breath. The degree of severity of pneumonia depends on factors such as age, general health condition, and the origin of the infection.1 Although pneumonia can occur in people of all ages, the age groups most at risk for developing pneumonia and of it becoming severe are children aged 2 years and younger, and persons over 65 years of age.1 In fact, it has been reported that, compared to other age groups, the highest overall pneumonia mortality rate is reported in people aged 70 years or older, with 261 pneumonia deaths per 100 000 people in 2017 for this age group.2 Moreover, also in 2017, the overall mortality rate for pneumonia was 15 deaths per 100 000 people.2

In the United States, pneumonia was the most common primary diagnosis in hospitalized patients in 2014 (41.2% in intensive care unit [ICU] patients and 36.6% in inpatients), and respiratory diseases were the most common cause of death in patients with two or more prior emergency department visits (36.1%) and the second most common cause in those with one prior emergency department visit (25.9%).3 In Colombia, in 2010, the population aged 80 years or older was the age group with the highest annual consultation and hospitalization rates (873 consultations and 100 hospitalizations per 1 000 person-years, respectively), while lower respiratory tract infection was the disease with the second highest annual incidence rate (2 232 new cases per 100 000 persons).4

Besides its impact in terms of morbidity and mortality, and because the use of antimicrobials is one of the therapeutic options to be considered in pneumonia, its proper diagnosis and treatment has an impact on the development of antimicrobial resistance. Since 2014, this situation has been considered a public health problem by the World Health Organization (WHO),5 which included community-acquired microorganisms such as Streptococcus pneumoniae, one of the main etiological agents of community-acquired pneumonia (CAP), in the list of species of greatest concern for antimicrobial resistance.6 CAP is defined as acute parenchymal lung infection that is acquired in a community setting and is not associated with health care in a hospital, nursing home, or other health care setting.7

Therefore, establishing guidelines to direct the treatment of this group of patients is important in order to obtain better clinical outcomes and promote a rational use of antibiotics in this setting. In Colombia, the last national guideline for the management of CAP was published in 2013,8 so it is necessary to review and update the recommendations for the management of this infection in the country, without overlooking the specific recommendations for the care of COVID-19 patients,9 which, depending on the need or appearance of new evidence, may be reviewed and updated eventually.

Scope of the clinical practice guideline (CPG)

This CPG is intended for health care workers involved in the care of adult patients (>18 years of age) with a clinical suspicion or confirmed diagnosis of CAP and for decision makers or entities involved in the generation of health policies related to the management of this condition. This CPG includes recommendations for the diagnosis and treatment of CAP in the Colombian context.

Objective of the clinical practice guideline

To systematically generate evidence-based clinical recommendations for the diagnosis and treatment of adult patients with a clinical suspicion or confirmed diagnosis of CAP in order to optimize the quality of health care provided to these patients in the country and, thus, obtain better clinical outcomes and promote the appropriate and safe use of antimicrobials in the treatment of this population.

Population targeted by the CPG

The recommendations contained in this CPG address the following patient groups:

  • Adult patients (>18 years)

  • Patients with clinical suspicion or confirmed diagnosis of CAP.

  • Patients with clinical suspicion or confirmed diagnosis of aspiration pneumonia.

Population not targeted by the CPG

The recommendations contained in this CPG do not include the following population groups:

  • Pediatric population (<18 years of age).

  • Pregnant women

  • Patients with clinical suspicion or confirmed diagnosis of health care-associated pneumonia.

  • Patients with clinical suspicion or confirmed diagnosis of ventilator-associated pneumonia.

  • Patients with acute exacerbation of chronic obstructive pulmonary disease.

  • Patients with primary or secondary immunodeficiency.

Intended users of the CPG

The recommendations contained in this CPG are aimed at health workers involved in the health care process of adult patients with a clinical suspicion or confirmed diagnosis of CAP at the different levels of health care of the Colombian General Social Security Health System (I, II, III, and IV), namely, general practitioners; specialists in emergency medicine, family medicine, internal medicine, critical medicine and intensive care, pulmonology, and infectious diseases; nurse practitioners; clinical laboratory staff; pharmaceutical chemists; and other personnel involved in the diagnosis and treatment of patients with CAP.

Methodology

This CPG was developed in accordance with the standards established in the Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia (Methodological Guidelines for the Implementation-Adaptation of Evidence-Based Clinical Practice Guidelines) of the Ministry of Health and Social Protection of Colombia,10 as described below.

Composition of the guideline development group

The guideline development group (GDG) consisted of eight members distributed as follows: two specialists in adult infectious diseases (JAC, SIC), four specialists in adult pulmonology (EAS, AS, JVT, DPA), one specialist in internal medicine (LCN), and two clinical epidemiologists with experience in the development of CPGs, systematic literature reviews, synthesis and qualification of evidence, and participatory processes (JAC, MCV).

Prior to the start of the development of the GPC, each of the GDG members declared whether or not they had conflicts of interest by filling out a conflict-of-interest disclosure form designed for this purpose. When a conflict of interest was declared, an analysis was carried out to define its impact on the member's participation in the different CPG development activities.

The scope and objectives of the CPG, as well as the aspects to be addressed, were defined during informal consensus meetings in which all members of the GDG participated.

GPC search

Once the scope and objectives of the CPG were established, a systematic search of CPGs was conducted to identify guidelines published in any language between 2015 and 2020 that addressed the issues set out in the scope of the present guideline.

The websites of the following CPG compilers and developers were consulted: Guidelines International Network, Agency for Healthcare Research and Quality/National Guidelines Clearinghouse, CMA Infobase: Clinical Practice Guidelines, Catálogo de Guías de Práctica Clínica en el Sistema Nacional de Salud (Guía Salud), National Institute for Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network, New Zealand Guidelines Group, and American College of Physicians.

Systematic searches were also performed in MedLine, LILACS and Epistemonikos using search strategies adapted for each search engine and utilizing Boolean, truncation and proximity operators, as well as free-text terms and controlled vocabulary, including key terms such as "community-acquired infections" and "respiratory tract infections". The Medline search strategy is outlined in Supplementary Table 1.

Screening, quality assessment, and selection of CPGs to be used for the development of the guideline

Once the searches were performed, and after removing duplicates, two reviewers (MCV, LCN) independently performed the primary screening of the records retrieved by reading the title and abstract, selecting the documents classified as CPG or evidence-based recommendations that addressed at least one of the aspects defined in the scope of this guideline. Subsequently, two reviewers (MCV, LCN) independently performed the secondary screening (full-text reading) of the references selected in the previous step, using the modified 7 tool (i.e., Guideline Implementability Appraisal tool) proposed in the Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia of the Colombian Ministry of Health and Social Protection.10 Disagreements on the inclusion of a CPG were resolved by consensus or through the intervention of a third reviewer in cases where agreement between the two reviewers could not be reached.

Even though, as mentioned above, there were no publication language restrictions in the CPG searches, studies published in languages such as German, Japanese or Korean were excluded during the full-text reading screening stage and only those published in English or Spanish were taken into account, because the reviewers were not fluent in the former languages.

Next, the selected CPGs were presented to the development group in order to evaluate their methodological quality using the AGREE II tool.11 Each guideline was evaluated independently by three reviewers, and at least one clinical expert and one methodological expert always participated in the process. Furthermore, when there was doubt as to the information available for the evaluation of the CPG, additional information from the developer groups was requested by email.

After completing the quality assessment process, CPGs with a score >60% in the domains of methodological rigor and editorial independence were selected. Finally, in accordance with the recommendations of the Guía Metodológica Adopción - Adaptación de Guías de Práctica Clínica Basadas en Evidencia of the Colombian Ministry of Health and Social Protection,10 and with the aim of selecting the CPGs to be used in the adaptation process, the GDG analyzed the selected guidelines taking into account the following aspects: the topics addressed in the guidelines, the use of the GRADE methodology, the year of publication, and the date of the last search for evidence reported in the guideline.

Based on the methodology described above, two CPGs were selected for the adaptation process, namely, the American Thoracic Society and Infectious Diseases Society of America (ATS / IDSA) CPG: Diagnosis and Treatment of Adults with Community Acquired Pneumonia, an Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America,12 and the National Institute for Clinical Excellence (NICE) CPG: Pneumonia (community-acquired): antimicrobial prescribing [NG138],13 both published in 2019. To adapt the recommendations to the Colombian context, authorization was obtained from the authors of both CPGs (Metlay JP and NICE).

Adaptation of recommendations

The GDG carried out the adaptation process using the GRADE methodology, (specifically the GRADE EtD tool),14,15 based on the information provided in the two selected CPGs. The GRADE evidence profiles were also included along with the evaluation of the certainty of the evidence, which was completed by analyzing each of the following domains: number and design of studies, risk of bias, inconsistency, indirect evidence, imprecision, and other considerations. All this was done taking into account considerations specific to the Colombian context, the benefits and harms of the different options, the use of resources, the impact on equity, and the feasibility of implementation.

Expert consensus

The adapted recommendations were presented at three expert consensus meetings with the participation of representatives from different health sciences disciplines and scientific societies ("Asociación Colombiana de Infectología - ACIN [JP, FOG, IR], Asociación Colombiana de Neumología y Cirugía del Tórax - Asoneumocito [FM], Asociación Colombiana de Medicina Interna - ACMI, Asociación Colombiana de Medicina Crítica y Cuidado Intensivo - AMCI [JARC], professionals in the areas of microbiology, respiratory therapy, pharmacy, nursing and health auditing [ALL, IJG, SLC, JAD, NG, FG]), as well as patient representatives (Asociación de usuarios de Méderi [JEM, MP]), thus including the perspective of the various stakeholders.

At the consensus meeting, through a participatory process using Delphi methodology in real time and taking into account the information and evidence provided by the two selected CPGs and the considerations specific to the Colombian context suggested by the clinical experts, recommendations were formulated and graded according to the GRADE16 methodology, and good practice points were formulated, which allow good clinical practice in patient management.

Voting during consensus was conducted anonymously and electronically. Agreement was defined as reached if more than 50% of the voters were in favor or against a recommendation or good practice point. In cases in which no agreement was reached in the first round, a discussion session was held followed by a new voting round; a maximum of three voting rounds were allowed for each recommendation and/or good practice point.

Quality of evidence grades

  • High: We are very confident that the true effect is close to the estimate of effect.

  • Moderate: We are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it could be substantially different.

  • Low: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.

  • Very low: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.

Implications of strong and weak recommendations

Implications of a strong recommendation are:

  • For patients: Most individuals in this situation would want the recommended course of action and only a small number would not.

  • For clinicians: Most individuals should receive the recommended course of action.

  • For policy makers: The recommendation can be adapted as policy in most situations.

Implications of a weak (conditional) recommendation (suggestion) are:

  • For patients: The majority of individuals in this situation would want the suggested course of action, but many would not.

  • For clinicians: Recognize that different choices will be appropriate for different patients, and that you must help each patient arrive at a management decision consistent with her or his values and preferences.

  • For policy makers: Policy making will require substantial debates and involvement of many stakeholders.

Questions addressed in the guidelines

  1. Should sputum Gram stain and culture be performed for diagnosing CAP in adults?

  2. Should blood cultures be performed for diagnosing CAP in adults?

  3. Should urinary antigen testing be performed for diagnosing CAP in adults?

  4. Should influenza virus testing be used for diagnosing CAP in adults?

  5. Should clinical prediction rules be used to determine the healthcare setting in which adult CAP patients should be treated?

  6. Should the procalcitonin test be used to define the initiation of antimicrobial therapy in adults with CAP?

  7. What is the best strategy for empirical antimicrobial therapy in adult outpatients with CAP?

  8. What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP?

  9. What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa?

  10. What is the appropriate duration of antimicrobial therapy in adult patients with CAP, both outpatients and inpatients?

  11. What is the appropriate route of administration of antimicrobial therapy in adult patients with moderate to severe CAP?

  12. Should antiviral therapy be included in the treatment of adult patients with CAP who test positive for influenza?

  13. Should corticosteroids be used in adult inpatients with CAP?

Recommendations and evidence review

Microbiological diagnosis

Question N° 1. Should sputum Gram stain and culture be performed for diagnosing CAP in adults?

Recommendations

  • We do not recommend routine sputum Gram stain and culture in adult outpatients with CAP (strength of recommendation: strong against; quality of evidence: very low ⨁◯◯◯).

  • We recommend performing Gram stain and culture of lower respiratory tract secretions prior to initiating antimicrobial therapy in hospitalized adult patients with CAP who:

  • ° Have been diagnosed with severe CAP (Table 1) (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or

  • ° Are receiving empiric antimicrobial therapy for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or

  • ° Have a history of MRSA or P. aeruginosa infection, especially patients with previous respiratory tract infection with one of these pathogens (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯); or

  • ° Have a history of hospitalization and antimicrobial therapy in the last 90 days (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯).

Table 1: Criteria for severity of community-acquired pneumonia.

CAP is considered severe if the patient meets 1 major or 3 or more minor criteria.

Source: Adapted from Mandell et.al. 17

Good clinical practice point

Respiratory tract specimen quality should be judged based on the Murray & Washington criteria,18 and the report should be interpreted only if the specimen result is category 2 or 3. See Table 2.

Table 2: Murray & Washington criteria.

Source: Adapted from Murray & Washington.1

Rationale for the recommendation

Gram staining is an easy and quick test that can be performed in most health institutions, even in low complexity centers. Initially designed to identify S. pneumoniae, it allows to rapidly determine the microbial etiology of CAP. Conversely, sputum culture entails more difficulty due to the usual limitations for the growth of S. pneumoniae and a number of important causative microorganisms, especially intracellular bacteria.

In clinical practice, according to what has been reported in the literature, the results of sputum Gram stain or culture may have a very limited impact on decisions regarding the treatment of CAP in the outpatient setting. Given the low quality of evidence of the benefit of performing cultures of respiratory specimens from adult patients with CAP in the outpatient setting, the consensus group agreed to recommend against performing sputum Gram stain and culture in this context.

However, there are two cases in which sputum culture and Gram stain are recommended. The first is endotracheal aspirate culture in patients with severe CAP requiring intensive care with endotracheal intubation, since McCauley et al. 19 found that, for intubated patients with CAP, tracheal aspirate culture was the only positive test in 39% of cases (32 of 89) when other diagnostic tests such as blood cultures and urinary antigen tests were negative. The second case in which we recommend performing sputum culture and Gram stain is patients with suspected MRSA or P. aeruginosa infection to confirm their etiology and/or adjust antibiotic treatment based on the results of these tests; although evidence on risk factors associated with the presence of these microorganisms is not solid, it has been reported that situations such as a history of infection by these bacteria and previous antibiotic treatment or hospitalization in the last 90 days may be associated with an increased risk of MRSA or P. aeruginosa.

In addition, sputum cultures on admission in referral hospitals may be helpful in decision-making regarding antimicrobial therapy in these patients, as well as in identifying those who have been admitted with previous airway colonization. This recommendation aims to promote the rational use of antimicrobials when treating these patients by enabling the adjustment of the antimicrobial scheme once the culture results are available.

Summary of evidence

The studies that were identified to establish these recommendations are observational and, in general, the quality of the evidence is very low. Firstly, the criteria for differentiating patients with severe CAP are set out in Table 1,17 while the Murray and Washington criteria for interpreting the sputum Gram stain are presented in Table 2.18 Signori et al, 20 in a study involving 274 hospitalized patients with CAP, evaluated the frequency of sputum culture and its association with mortality, finding a mortality rate of 32.7% in patients who did not present with expectoration (n=58), 20.9% in patients with expectoration but from whom sputum samples were not collected for culture (n=124), and 6.5% in patients from whom sputum samples were collected for culture (n=124), with a higher risk of mortality in the group with expectoration but from whom sputum samples were not collected (OR: 3.78, 95%CI: 1.40-10.23). Moreover, in the study by Uematsu et al., 21 conducted in Japan with data from 65 141 adult hospitalized patients with CAP, no association was found between sputum testing and 30-day mortality (OR: 1.06, 95%CI: 0.98-1.15; p=0.013), nor with length of hospital stay (HR: 0.98, 95%CI: 0.97-1.00; p=0.071).

Studies on the usefulness of sputum Gram staining in the hospital setting, such as the one conducted in Japan by Sato et al. 22 in 144 CAP cases requiring hospitalization, have shown no significant difference in length of hospital stay (9.67 days with the test vs. 11.75 days without the test, p=0.053) nor in time on intravenous antimicrobial therapy (6.73 days with sputum Gram staining vs. 7.91 days without the test, p=0.44). These findings have been confirmed in other studies on microbiological testing that have shown that establishing an etiologic diagnosis using sputum Gram stain or culture routinely in settings with a low frequency of resistant pathogens does not have a significant impact on mortality, length of hospital stay, changes in antimicrobial therapy, or the overall clinical prognosis of these patients.23,24

In Colombia, there is insufficient information to evaluate the economic impact of the implementation of these recommendations. In the existing literature, no local data on the costs of medical care for CAP were found. Although the consensus meeting took into account data on the costs of some supplies, medications, hospitalization, among other factors involved in the care of these patients in the country, it was not possible to make an actual assessment of the cost-effectiveness of these recommendations. There were also no studies that allowed us to evaluate, from any perspective, the effect of the recommendations on health equity in minority or disadvantaged populations. These two aspects were considered as issues to be investigated in Colombia in order to better establish potential recommendations in future versions of the guideline.

Question N° 2. Should blood cultures be performed for diagnosing CAP in adults?

Recommendations

We do not recommend performing blood cultures in adult outpatients with CAP (strength of recommendation: strong against; quality of evidence: good: ⨁◯◯◯).

We recommend performing blood cultures prior to initiating antimicrobial therapy in hospitalized adult patients with CAP who:

  • Have been diagnosed with severe CAP (Table 1) (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or

  • Have risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯); or

  • Have a history of MRSA or P. aeruginosa infection, especially patients with a history of respiratory tract infection by one of these pathogens (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯); or

  • Have a history of hospitalization and antimicrobial therapy in the last 90 days (strength of recommendation: weak for; quality of evidence: very low ⨁◯◯◯).

Good clinical practice point

The blood culture set should be collected according to the parameters defined in the manual of procedures for sample collection issued by the Instituto Nacional de Salud (National Health Institute or INS by its acronym in Spanish).25

Rationale for the recommendation

Blood cultures allow the identification of microorganisms in the blood at the time of CAP diagnosis. However, most patients will not present with bacteremia, which is limited to S. pneumoniae, S. aureus, and Enterobacteriaceae infections, and to patients with comorbidities or severe forms of the disease.

Evidence on the benefit of performing blood cultures in all CAP patients has a very low quality, so the recommendation is limited to certain groups of patients who could be considered at higher risk, such as those with severe CAP or with risk factors for microorganisms such as MRSA or P. aeruginosa. In addition, routine performance of this test may lead to false positives that promote indiscriminate use of antimicrobials in the context of CAP treatment. Another reason for not recommending the routine performance of blood cultures is that results may take more than 48 hours, so treatment adjustment may be delayed or no longer relevant in outpatients or inpatients with mild or moderate CAP.

Summary of evidence

The reviewed studies on the usefulness and benefit of taking blood cultures in CAP patients are observational. For instance, Meehan et al., 26 in a study evaluating which care strategies in hospitalized CAP patients were associated with mortality outcome in a sample of 14 069 older adults (>65 years) hospitalized in different parts of the United States, found that the performance of blood cultures, both before initiating antibiotic administration and within the first 24 hours of administration, did not show a benefit with respect to 30-day mortality (adjusted OR: 0.92, 95%CI: 0.82-1.02; p=0.10 and adjusted OR: 0.90, 95%CI: 0.81-1.00; p=0.07).

Similarly, another study conducted in the United States in 1 062 adult inpatients with CAP reported that the performance of blood cultures within the first 24 hours after hospital admission or before the administration of antimicrobials had no impact on mortality (adjusted OR: 0.86, 95%CI: 0.36-2.07 and adjusted OR: 1.21, 95%CI: 0.62-2.34, respectively), nor on length of hospital stay (adjusted OR: 1.04, 95%CI: 0.72-1.50 and adjusted OR: 0.84, 95%CI: 0.60-1.17, respectively). However, there was an association between performing blood cultures during the first 24 hours after hospital admission and an increased risk of clinical instability at 48 hours (adjusted OR: 1.62, 95%CI: 1.13-2.33).27

Along these lines, Costantini et al., 28 in a study comparing two cohorts of CAP patients admitted to a hospital in Italy in 2005 (n=234) and 2012 (n=321), found that the performance of this test was not associated with a benefit for in-hospital mortality (OR: 0.67, 95%CI: 0.37-1.21), nor for 30-day mortality (OR: 0.6, 95%CI: 0.32-1.09). Finally, it has been described that, in the context of routine blood culture performance in patients with non-severe CAP, the rate of contaminated blood cultures is 3.1% and that, consequently, it is likely that there are many more false positives (e.g., growth of coagulase-negative staphylococci that colonize the skin of patients and are not related to CAP) than true positives, thus promoting the indiscriminate use of antibiotics in the treatment of these patients.29

Question No. 3. Should urinary antigen testing be performed for diagnosing CAP in adults?

Recommendations

  • We suggest performing pneumococcal urinary antigen testing in adults with severe CAP (Table 1) (strength of recommendation: weak for; quality of evidence: low ⨁⨁◯◯).

Rationale for the recommendation

Randomized clinical trials of urinary antigen testing for Legionella and S. pneumoniae have not shown a clear benefit in terms of clinical outcomes in patients with severe CAP requiring ICU management. On the other hand, observational studies unfortunately have a low quality, and their results are often contradictory: some suggest that urinary antigen testing for Legionella is associated with a decrease in mortality in hospitalized patients with CAP, while others conclude that there is no such benefit.

Furthermore, no studies evaluating only the role of urinary antigen testing in hospitalized patients with severe CAP were found; instead, the studies include other diagnostic laboratory tests and multiple care strategies, so it is unclear whether the results can be attributed to urinary antigen testing alone or to diagnostic and therapeutic strategies in general. Although Legionella infection carries a high burden in terms of mortality in the context of severe CAP, we consider that the benefit of performing urinary antigen testing to determine its presence is very limited considering that this microorganism would already be covered by the empirical antimicrobial treatment scheme implemented in CAP patients considered to be at high risk. Regarding the performance of pneumococcal urinary antigen testing, the consensus group agreed to recommend this practice in patients with severe CAP, since it has been reported that its use may be related to a decrease in mortality.28

Summary of evidence

Evidence on the use of urinary antigen testing for detecting microorganisms when diagnosing CAP is conflicting. For example, Costantini et al 28 found that taking these tests, including pneumococcal and Legionella urinary antigen tests, was associated with a decrease in in-hospital mortality and 30-day mortality (OR: 0.427, 95%CI: 0.215-0.850 and OR: 0.341, 95%CI: 0.170-0.685, respectively), a finding also reported by Uematsu et al. 21 for 30-day mortality (OR: 0.75, 95%CI: 0.69-0.82; p<0.001).

On the other hand, Falgera et al.,30 in a study of 177 hospitalized CAP patients evaluating the impact of a treatment strategy based on the urinary antigen test result (n=88) compared to empirical treatment (n=89), showed, in a intention-to-treat comparative analysis, that the performance of this test did not have any benefit in terms of mortality, clinical relapse, ICU admission, days of hospital stay, need for readmission, adverse events, duration (in days) of antimicrobial treatment, and duration (in days) of intravenous treatment.

Question N° 4. Should influenza virus testing be used for diagnosing CAP in adults?

Recommendations

We recommend testing for influenza viruses, preferably using rapid molecular assays for influenza viral RNA or nucleic acid detection, rather than the rapid influenza antigen detection test in patients:

  • Diagnosed with severe CAP (Table 1) (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯), or

  • Who have a comorbidity (respiratory, cardiovascular or immunosuppression) (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯).

Rationale for the recommendation

Evidence on the usefulness of testing for influenza viruses in patients with CAP is scarce; moreover, the reported results are controversial. Available information comes from studies conducted in patients with lower respiratory tract infection, in a group of individuals with CAP, and not in a population of patients infected only with influenza. Epidemiological studies have reported that the prognosis of patients with severe CAP or CAP and comorbidities worsens when they have an infection caused by one of the influenza viruses, so the consensus group decided to recommend molecular assays for influenza viral RNA or nucleic acid detection in these two clinical scenarios.

Summary of evidence

No studies evaluating the usefulness of testing for influenza viruses in patients with CAP were found. The few papers found involved individuals with lower respiratory tract infection, such as the randomized clinical trial conducted by Oosterheert et al.31 in 107 patients (51.4% with CAP) to evaluate the feasibility and clinical and economic impact of using the TaqMan PCR test for the detection of respiratory viruses and atypical pathogens, in which it was found that, compared to the control group (n=52; use of conventional diagnostic procedures) there was no change in 28-day mortality, duration of antimicrobial treatment, or length of hospital stay.

Treatment

Question N° 5. Should clinical prediction rules be used to determine the healthcare setting in which adult CAP patients should be treated?

Recommendations

  • We recommend using clinical judgment along with a validated clinical prediction rule, either the pneumonia severity index (PSI) or the CURB-65 or CRB-65 pneumonia severity scores, to assess the severity of illness and determine the need for hospitalization in adults diagnosed with CAP (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯).

Good clinical practice point

  • Clinical judgment, along with the 2007 IDSA/ATS pneumonia severity criteria, should be used to determine the level of inpatient care in adults diagnosed with CAP who do not require vasopressors or mechanical ventilation.

  • Adults with CAP and hypotension requiring vasopressor therapy or with respiratory failure requiring mechanical ventilation should be admitted directly to the ICU.

Rationale for the recommendation

The use of clinical prediction rules to determine where patients with CAP should be treated (outpatient setting, general ward, or ICU) has been shown to be more effective and safer than clinical judgment, reducing variability in this decision among health care professionals. For patients with CAP classified for outpatient treatment and follow-up, a decrease in the cost of care and in the development of complications associated with inpatient treatment has been reported.

Even though the use of the severity and clinical prediction scores may vary because, depending on the level of care, laboratory and diagnostic tests required to calculate the values of these scores are not available in all health care centers, we recommend using one of these scores, with no preference in particular, to determine the health care setting in which these patients should be treated. In any case, besides the use of clinical prediction rules, the decision must be made taking into account clinical judgment, which includes the variability of the aspects considered in the prediction rules as well as socio-demographic, economic and support network factors of the patient.

Summary of evidence

Clinical prediction rules such as the PSI and CURB-65 pneumonia severity scoring system use demographic variables and clinical data obtained from laboratory and diagnostic tests to determine the prognosis of patients with CAP, especially 30-day mortality outcome.32-34 In this regard, Marrie et al.,35 in a multicenter controlled clinical trial conducted in 1 743 patients with CAP treated at the emergency department aimed to determine whether a critical care strategy that included clinical prediction rules had benefits in the treatment of these patients, found that using the PSI was a superior strategy in terms of classifying patients requiring outpatient treatment compared to not using any clinical prediction rules. They also found that the use of this score showed a benefit in terms of length of hospital stay, with a reduction in hospital readmission. These findings have been confirmed in other studies that have demonstrated that the use of the PSI in this population is safe, especially for selecting patients who only require outpatient care, and that this score has greater discriminating power to define the initial place of treatment for patients with CAP, without increasing the risk of mortality or morbidity.36,37

Studies on other clinical prediction rules for pneumonia are scant and results are less consistent. For example, in the case of the CURB-65 score, a randomized trial conducted in New Zealand comparing a group of patients with CAP who received inpatient treatment on a general ward (n=25) with a group who received outpatient treatment (n=24) had limitations in determining the differences between the two treatment strategies. One of them was related to the intravenous administration of antimicrobials under the supervision of nursing staff in the outpatient setting, which is a practice that is typical of the hospital setting and is referred to as "hospital-at-home" in several regions.38

The CURB-65 score includes simple variables that can be routinely recorded in the medical records, without the need for additional laboratory tests other than the blood urea nitrogen test, which facilitates its use in less complex health care settings and makes it an easier tool to use compared to other clinical prediction rules.39 In this regard, Aujeski et al., 40 in a study performed in 3 181 patients with CAP seen in the emergency departments of 32 hospitals of the United States and in which the performance of the PSI, CURB-65 and CURB clinical prediction rules for predicting 30-day mortality was evaluated, found that the diagnostic performance of the PSI was superior with an ROC curve of 0. 81 (95%CI: 0.78-0.84), showing a significant difference (p<0.01) in comparison with the other two scores (CURB: AUC=0.73, 95%CI: 0.68-0.76; CURB-65: AUC=0.76, 95%CI: 0.73-0.80).40

Question N° 6. Should the procalcitonin test be used to define the initiation of antimicrobial therapy in adults with CAP?

Recommendations

  • We do not recommend performing procalcitonin (PCT) test in adults with clinically suspected CAP confirmed by imaging studies to decide, based on the test results, to initiate antimicrobial therapy (strength of recommendation: strong against; quality of evidence: moderate ⨁⨁⨁◯).

Rationale for the recommendation

Some of the studies that have described the use of the PCT test to determine the initiation of antimicrobial therapy in patients with CAP do not clearly meet the diagnostic criteria for pneumonia, and some do not even include the performance of an imaging study to confirm the diagnosis. For this reason, results about the benefit of performing this test in these patients may not be sufficiently reliable and conclusions may be controversial. For the GDG, the latter factor has the greatest weight for not recommending the PCT test to determine the initiation of antimicrobial therapy, since, in several clinical trials, patients with PCT values below the cut-off point for this serum marker and in whom antimicrobial treatment has not been initiated have favorable outcomes, while other patients with the same characteristics do not have a similar clinical course.

Other factors were considered that, based on the experience of the consensus group's experts, do not support the use of this test in this context, including cost, the fact that it is not readily available at the various levels of health care, and the typical delay in reporting the results in some health care centers (up to 72 hours).

Summary of evidence

Several studies have attempted to establish a reliable cut-off point for the serum PCT level to differentiate a CAP of viral etiology from one of bacterial origin, but so far it has not been possible to establish a standard threshold, although it is clear that the higher the value, the more likely it is that the origin is bacterial.41 For instance, the study conducted in Switzerland by Christ-Crain et al 42 in 243 patients (35.40% with CAP) found that the adjusted relative risk (RR) of antibiotic exposure was 0.49 (95%CI: 0.44-0.55; p<0.0001) in the group in which the PCT test was used (n=124) compared to the standard group (clinical trial only); however, other clinical outcomes such as mortality, length of hospital stay or development of complications were not evaluated.42 Likewise, a randomized controlled clinical trial conducted in Switzerland in 302 patients diagnosed with CAP reported that the use of PCT levels reduced antibiotic exposure (RR: 0.52, 95%CI: 0.48-0.55; p<0.01), antibiotic prescriptions on admission (85 vs. 99%; p<0.01), and duration of antibiotic treatment (median: 5 vs. 12 days; p <0.01), but, again, no prognostic clinical outcomes were assessed, and neither the length of hospital stay nor the risk of clinical failure.43

Regarding the evaluation of the impact of using this biomarker in terms of adverse effects, Schuetz et al, 44 in a randomized controlled clinical trial conducted in 1 359 patients with lower respiratory tract infection admitted to the emergency departments of 6 hospitals in Switzerland, 68.1% of whom had CAP, found that, considering the reduction in the duration of antibiotic treatment, patients in the PCT group (n=671) had a lower risk of adverse events associated with antibiotic use. However, concerning undesirable outcomes such as death, ICU admission, disease-specific complications, or recurrent infection requiring antibiotic use during the last 30 days, the use of a PCT algorithm was not superior to the use of treatment strategies based on clinical judgment.

Furthermore, the limitations for its implementation in Colombia should be taken into account, since the PCT test is not available in all health care centers and its use is widely limited because it is not included in the health benefits plan. Consequently, given the importance of initiating antimicrobial treatment in a timely manner, its use could entail a delay in the initiation of antibiotic administration in patients who require it.

Question N° 7. What is the best strategy for empirical antimicrobial therapy in adult outpatients with CAP?

Recommendations

  • We recommend using amoxicillin or, in case of penicillin allergy, doxycycline or clarithomycin, in adult patients diagnosed with CAP treated in the outpatient setting and without risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯).

Good clinical practice point

Quinolones should be avoided in the treatment of CAP.

Rationale for the recommendation

For this recommendation, the consensus group considered studies conducted in patients with CAP treated in the outpatient setting. To establish the first-line antimicrobial treatment, the most frequent etiological microorganisms in this population were considered; the proposed antimicrobial treatment schemes do not include coverage of atypical bacteria because no harmful outcomes have been reported in patients with CAP treated with amoxicillin. Another aspect in favor of the use of amoxicillin in monotherapy is that there are a large number of studies on the safety of this antimicrobial.

In cases in whom amoxicillin is contraindicated, such as patients with a history of allergy to this antibiotic, the consensus group recommended the administration of doxycycline or clarithromycin. These antimicrobials were not considered as first-line treatment for two reasons: first, the additional adverse effects of macrolides related, in particular, to electrocardiographic changes, arrhythmias, and increased risk of sudden death, and second, to promote the rational use of antimicrobials in this clinical setting.45

Finally, the use of this group of drugs for the treatment of CAP should be avoided as a good practice point bearing in mind that quinolone antibiotics increase the risk of inducing antimicrobial resistance in Gram-positive cocci and enterobacteria; the fact that they are used as second-line treatment for tuberculosis, an endemic disease in Colombia; and the frequency and severity of adverse effects related to the administration of these antibiotics.46,47 Prescription of antimicrobials should be based on the antibiotic susceptibility profile of the microorganisms causing CAP in each health care center. See Table 3 48-52 and Table 4.

Table 3: Frequency of microorganisms causing CAP in Colombia.

n*: number of patients.

n+: number of adults aged 65 and over.

n++ number of adults with severe CAP.

Source: Own elaboration.

Table 4: Antimicrobials and recommended dosages for the treatment of adult patients with CAP.

Source: Own elaboration.

Summary of evidence

Data on the superiority or non-inferiority of antimicrobials in patients with CAP receiving outpatient treatment are scarce, as documented by a Cochrane review conducted in 2014.53 For example, Maimon et al., 54 found no significant differences in terms of morbidity or mortality, despite the fact that some antimicrobials did not cover atypical bacteria, in a meta-analysis that included five studies comparing the usefulness of macrolides vs. fluoroquinolones in the outpatient treatment of CAP; three comparing macrolides vs. beta-lactams; three comparing fluoroquinolones vs. beta-lactams; and two comparing cephalosporins vs. beta-lactam beta-lactamase inhibitors.

Similarly, Bonvehi et al., 55 in a study conducted in Argentina in 327 outpatients with CAP comparing the use of clarithromycin (n=160) vs. amoxicillin+clavulanate (n=167), reported that there were no significant differences between groups in clinical and microbiological response rates, nor in the presence of adverse effects. On the other hand, studies that have evaluated the usefulness of amoxicillin in this clinical setting have reported that, compared to the use of other antimicrobials such as broad-spectrum quinolones, the use of high doses of this drug has not shown any significant difference in terms of clinical success and adverse effects.56,57

Information on the frequency of microorganisms causing pneumonia in Colombia is limited. In general, three groups of microorganisms have been described: classical bacterial agents with a high virulence potential, including S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus; intracellular microorganisms, usually grouped as atypical, which include Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella spp, and Coxiella burnetii; and viruses, most notably influenza viruses, respiratory syncytial virus, rhinoviruses, coronaviruses, adenoviruses and, recently, SARS CoV-2 in the adult population. Table 3 presents information on the relative frequency of the most frequent microorganisms reported by Colombian studies conducted in patients with CAP.

The frequency of Streptococcus pneumoniae isolates in Colombia, as well as the relative frequency of the different serotypes and their antimicrobial resistance, has varied after the introduction and extensive use of pneumococcal vaccines in the Expanded Program for Childhood Immunization. Although penicillin resistance decreased during the first few years after its inclusion, penicillin, ceftriaxone, and macrolide resistance rates in S. pneumoniae isolates have increased in recent years due to the selection of certain serotypes not covered by the vaccine.58

Furthermore, according to data from the National Public Health Surveillance System - SIVIGILA, since 2017 the proportion of isolates that are not sensitive to macrolides and penicillins or ceftriaxone in adults is greater than 25% and 10%, respectively.59 This suggests that epidemiological surveillance for this microorganism should be maintained in the country, although the impact of its resistance to antimicrobials is still unclear in the context of pneumonia,60 and more studies are needed in this regard.

Question N° 8. What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP?

Recommendations

Patients with moderate CAP:

  • We recommend using the following antimicrobial therapy in hospitalized adult patients with a diagnosis of moderate CAP and no risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):

  • ° Monotherapy with a beta-lactam (ampicillin/sulbactam) and re-evaluation 48 to 72 hours after treatment initiation to consider the need to add a macrolide (clarithromycin), taking into account aspects such as worsening of vital signs, ability to eat, and mental status.

In case the patient is allergic to penicillin, it is recommended to use (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):

  • Monotherapy with ceftriaxone; or

  • Monotherapy with cefuroxime; or

  • Monotherapy with doxycycline.

Patients with severe CAP:

  • We recommend using the following antimicrobial therapy in hospitalized adult patients with a diagnosis of severe CAP (Table 1) and no risk factors for MRSA or P. aeruginosa (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):

  • ° Combination therapy with a beta-lactam (ampicillin/sulbactam) and clarithromycin.

  • If the patient is allergic to penicillin, we recommend using (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯):

  • ° Combination therapy with ceftriaxone (instead of ampicillin/sulbactam) and clarithromycin.

Good clinical practice point

  • Quinolones should be avoided in the treatment of CAP.

  • Anaerobic coverage should not be added to the treatment scheme for suspected aspiration pneumonia unless lung abscess or empyema are suspected.

Rationale for the recommendation

Recommendations for the treatment of CAP patients in the hospital setting are based on the treatment of the microorganisms that most frequently cause infection. There is no strong evidence on the benefits of using macrolides or antibiotics for the treatment of atypical bacteria in hospitalized patients with moderate CAP; studies comparing monotherapy with beta-lactam vs. beta-lactam with macrolide have not reported significant differences in that scenario. In the case of severe CAP, we recommend using a macrolide considering the coverage of atypical bacteria with high mortality burden such as Legionella and the additional effects of this group of drugs, such as modulation of inflammation. Furthermore, taking into account the quinolone resistance profile of the microorganisms that cause CAP and the adverse effects of these antibiotics, the use of this group of drugs for the treatment of these patients should be avoided as a good practice point. Antimicrobial prescription should be based on the antibiotic susceptibility profile of the microorganisms causing CAP in each health care center. See Tables 3 and 4.

Summary of evidence

Some studies have compared the use of beta-lactams with macrolides vs. monotherapy, although the latter with quinolones, and have reported that there are no differences between the two schemes; however, these studies have a low quality, small samples, and a non-inferiority design.61-63 Other research has evaluated the non-inferiority of beta-lactam and macrolide combination therapy vs. beta-lactam monotherapy, such as the open-label randomized clinical trial conducted by Garin et al. 64 in 580 patients with CAP hospitalized in 6 hospitals in Switzerland, which did not report a clear difference between arms (monotherapy arm, n=291 vs. combination therapy arm, n=289), but did suggest that patients with intracellular microorganisms took longer to achieve clinical stability.64

Nevertheless, the results reported by Garín et al. 64 differ from those described by Postma et al. 65 who compared various treatment strategies for CAP (beta-lactam monotherapy vs. fluroquinolone monotherapy vs. beta-lactam and macrolide combination therapy) in a cluster-randomized crossover clinical trial in 2 283 patients with mild to moderate CAP requiring hospitalization. The authors concluded that beta-lactam monotherapy was not inferior to the other antimicrobial treatment options for the outcomes of 90-day mortality and length of hospital stay, the latter being similar for all strategies.

These data, taken together, suggest that the benefit of using combination therapy in hospitalized patients with mild or moderate CAP is unclear, as its use does not offer any benefits in terms of reduced risk of progression to more severe forms of the disease and reduced length of hospital stay, but instead may contribute to increased antibiotics use, higher resource expenditure, and increased risk of adverse effects. As an alternative for the treatment of patients who are allergic to penicillin, the consensus group recommended the use of ceftriaxone, a therapy included in the non-inferiority studies of beta-lactam monotherapy referred to above. Likewise, as indicated in the systematic reviews and meta-analysis of Picard etal, 66 several clinical studies have evidenced the low frequency of cross-reactivity in allergic reactions in patients with a history of penicillin allergy who receive this drug. The next alternative in patients with a history of beta-lactam allergy is doxycycline, an antibiotic that has proven to be efficient due to its broad coverage of the causative microorganisms, as well as safe and cost-effective for the treatment of patients with mild to moderate CAP in the hospital setting.67

In patients with severe CAP, we recommend using beta-lactam plus macrolide to cover atypical bacteria such as Legionella, whose presence has been associated with a higher mortality rate, especially in older adults. In this regard, Nie et al, 68 in a meta-analysis that included 16 cohort studies (42 942 patients with CAP), reported a significant decrease in mortality in patients who received combination therapy (beta-lactam+macrolide) compared to those who received monotherapy (beta-lactam) (adjusted OR: 0.67, 95%CI: 0.61-0.73; p<0.01).

A similar finding was also described in the systematic review and meta-analysis (14 studies; 33 618 patients) by Horita et al.,69 specifically in patients with severe CAP, where the random-model meta-analysis yielded an OR for all-cause mortality for beta-lactam plus macrolide compared with beta-lactam monotherapy of 0.80 (95%CI: 0.69-0.92; p<0.01). Collectively, this evidence suggests the benefit of using combination therapy in patients with severe CAP, which is related either to antibiotic coverage of Legionella species that may be associated with increased mortality, or to the effect of combination therapy in patients with severe CAP caused by S. pneumoniae. 68

Question N° 9. What is the best strategy for empirical antimicrobial treatment in adult inpatients with CAP and with risk factors for MRSA or P. aeruginosa?

Recommendations

  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of moderate or severe CAP and previous respiratory isolate of MRSA (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):

  • ° Initiate antimicrobial therapy based on the microbiological report of the previous respiratory isolate AND

  • ° Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results OR

  • ° Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results AND initiate antimicrobial therapy with vancomycin or linezolid.

  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of moderate or severe CAP and previous respiratory isolate of P. aeruginosa (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):

  • ° Initiate antimicrobial therapy based on microbiological report of previous respiratory isolate AND

  • ° Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm need for continued therapy based on results OR

  • ° Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on the results AND initiate antimicrobial therapy with piperacillin/tazobactam or cefepime.

  • We suggest taking the following actions in hospitalized adult patients with a diagnosis of moderate CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for MRSA or P. aeruginosa (strength of recommendation: weak for; quality of evidence: low ⨁⨁◯◯):

  • ° Perform culture or PCR of upper respiratory tract specimen AND

  • ° Initiate antibiotic treatment covering MRSA or P. aeruginosa only if results are positive.

  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of severe CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for MRSA (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):

  • ° Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results AND initiate antimicrobial therapy with vancomycin or linezolid, along with measurement of vancomycin levels, if appropriate.

  • We recommend taking the following actions in hospitalized adult patients with a diagnosis of severe CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for P. aeruginosa (strength of recommendation: strong for; quality of evidence: low ⨁⨁◯◯):

  • ° Perform culture or PCR of upper respiratory tract specimen to adjust treatment or confirm the need for continued therapy based on results AND initiate antimicrobial therapy with piperacillin/tazobactam or cefepime.

Rationale for the recommendation

There are no clinical studies on predictors of MRSA or P. aeruginosa infection and there are no predictive scores to determine their presence. This, added to the fact that the prevalence of these microorganisms varies widely in each region and health care center in the country, led the consensus group to recommend the use of antimicrobials that cover MRSA or P. aeruginosa in patients with moderate to severe CAP and with a history of isolate of these microorganisms, as well as to perform culture or PCR of upper respiratory tract samples in order to establish a targeted treatment that promotes the rational use of antimicrobials.

The other clinical setting where we recommend antibiotic treatment of these bacteria is in patients with severe CAP and a history of hospitalization and/or antimicrobial therapy in the past 90 days or with locally validated risk factors for the presence of MRSA or P. aeruginosa. The strength of this recommendation is weak, and the evidence has a low quality because no studies were found to support the increased risk of MRSA or P. aeruginosa infection in the presence of these factors; however, due to the high mortality of patients with severe CAP, the use of antibiotics covering these bacteria should be considered in this clinical setting.

Summary of evidence

The main risk factor for suspecting infection by P. aeruginosa or MRSA is a history of infection or colonization by one of these microorganisms; in this regard, for example, an OR of 6.21 (95%CI: 3.25-11.85) has been described for MRSA.70 Other risk factors include the presence of respiratory comorbidities (OR: 5.8, 95%CI: 2.2-15.3; p<0.01), having a history of hospitalization (OR: 3.8, 95%CI: 1.8-8.3; p=0.02),71 especially in the last 90 days, and the use of antimicrobials in the last 90 days (OR: 2.90, 95%CI: 1.13-7.45; p=0.02).72 An additional risk factor that should be considered to initiate antibiotic coverage is the epidemiology of these infections in the health care center, which should include the local antimicrobial susceptibility profile.

In patients with moderate or severe CAP and in whom, depending on the presence of risk factors, MRSA or P. aeruginosa infection is suspected, cultures or PCR of respiratory samples should be performed to confirm this etiology and adjust antimicrobial treatment. This is explained by the fact that antimicrobial stewardship is relevant, as it has been shown to be safe and to reduce the duration of antibiotic treatment, the length of hospital stay, and the frequency of complications related to adverse effects of broad-spectrum antimicrobials.73

In this regard, Cremers et al. 74 found that, compared to no adjustment, adjusting antimicrobial therapy reduced mortality in patients with bacteremic nemococcal CAP (adjusted OR: 0.35, 95%CI: 0.12-0.99). Furthermore, Carugati et al., 75 in a study conducted with data from 261 hospitalized patients with CAP bacteremia, reported that adjustment of antimicrobial therapy (de-escalation) based on microbiological test results did not increase the risk of clinical failure in comparison with patients in whom antimicrobial therapy was de-escalated (RR: 0.89, 95%CI: 0.63-1.27; p=0.54). Nevertheless, in a recent large cohort study (88 605 hospitalizations due to CAP in the Veterans Affairs health care system medical centers), inverse propensity score-weighted regression of the weights showed that empirical use of linezolid or vancomycin in these patients did not decrease mortality but, on the contrary, increased it. 76

The costs of generic antimicrobials in Colombia are quite low and it is possible that the recommended therapeutic schemes are not expensive, both for intravenous and oral therapy. However, as mentioned above, formal evaluations of the cost-effectiveness of recommended treatments are needed in the region.

Question N° 10. What is the appropriate duration of antimicrobial therapy in adult patients with CAP, both outpatients and inpatients?

Recommendations

  • Patients with mild to moderate CAP:

We recommend that the duration of antimicrobial therapy should not exceed 5 days in total and considering the following criteria for discontinuation: clinical stability of the patient (resolution of alterations in vital signs [heart rate, respiratory rate, blood pressure, oxygen saturation, and body temperature]), adequate tolerance to oral administration of food and fluids, and no alteration in mental status (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯).

  • Patients with severe CAP:

We recommend establishing the duration of antimicrobial therapy depending on the patient's clinical course, microbiological test results, and biomarker levels (strength of recommendation: strong for; quality of evidence: moderate ⨁⨁⨁◯).

Good clinical practice point

If available, serum PCT testing may be used to determine whether to discontinue antimicrobial therapy in hospitalized patients.

Rationale for the recommendation

Taking into account that, in general, adequate antimicrobial prescription leads to clinical stability of patients 48-72 hours after starting treatment, we recommend a maximum duration of antimicrobial therapy of 5 days in patients with mild to moderate CAP and that discontinuation be decided based on clinical judgment, which includes criteria such as the absence of alterations in vital signs, adequate tolerance to oral administration of food and fluids, state of consciousness, and absence of complications. In cases of severe CAP, the duration of antimicrobial therapy should be established based on medical judgment, taking into account clinical and microbiological factors and monitoring of biomarkers such as serum PCT, if possible.

Summary of evidence

Historically, studies on the duration of antimicrobial treatment in patients with CAP have been grouped into two classes: a duration <7 days and a duration >7 days. The studies identified, such as that performed by el Moussaoui et al. 77 in 119 patients with CAP, compare the use of amoxicillin, initially intravenously for 3 days and then orally for 5 more days, with the use of placebo in patients with mild to moderate CAP, concluding that although both strategies showed similar results in the outcomes of resolution of symptoms and changes in x-ray findings, the frequency of adverse effects was greater in the group of patients in which antibiotics were administered for 7 or more days (21% vs. 11%).

These results have been confirmed by other studies such as the one conducted by Dunbar et al. 78 in 528 patients with mild to moderate CAP in which there was no statistically significant difference in clinical response rates or microbiological eradication rates between the use of levofloxacin for 5 days vs. the use of this drug for 10 days. Likewise, besides not finding discordant results between the duration of antibiotic treatment (7 days vs. 10 days) in hospitalized patients with severe CAP in terms of late recurrences or cure rates, Siegel et al. 79 reported a shorter length of hospital stay, a lower frequency of adverse effects, and lower costs in the group of patients who received antibiotic treatment with a shorter duration.

It should be noted that the use of scores to evaluate the possibility of implementing antimicrobial treatments of even 3 days has also been suggested, since these scores, some of which have been translated into and culturally adapted to Spanish,80 take into account the symptoms and the subjective clinical evolution of the patient to define the time of treatment.

Discontinuation of antimicrobial therapy should be based on the clinical stability of the patient, understood as the presence of normal vital signs, adequate tolerance to oral administration of food and fluids, and the absence of altered mental status; in this sense, these findings are expected to be observed in patients with mild to moderate CAP 2 to 3 days after initiation of antimicrobial therapy.81,82 Furthermore, the assessment of patients' clinical condition has been shown to reduce the length of hospitalization and duration of antimicrobial therapy, with no adverse impact on patient safety.83

Finally, it should be pointed out that there is currently no evaluation of the cost-effectiveness of the proposed interventions, although it is expected that they will be cost-effective, considering that they have the potential to reduce the length of hospital stay and, therefore, the possible associated complications, which would imply a reduction in the costs associated with the care of these patients since their use would allow early hospital discharge.

Question N° 11. What is the appropriate route of administration of antimicrobial therapy in adult patients with moderate to severe CAP?

Recommendations

  • We recommend using oral antimicrobials as first-line treatment in adult patients with moderate to severe CAP, always taking into account tolerance to oral administration of food/drugs/fluids and severity of infection (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯).

  • We recommend reassessing the patient's clinical condition 48 hours after starting intravenous antimicrobial therapy to consider switching to oral antimicrobials (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯).

Rationale for the recommendation

Initially, the route of administration of antimicrobials in patients with moderate to severe CAP was exclusively intravenous for the entire course of treatment. However, more recent studies have promoted the use of oral antimicrobials considering the decrease of adverse effects, the convenience of this route of administration, and the effectiveness of oral antimicrobial treatment, particularly in cases where 48 hours of intravenous therapy have already been completed and the patient is clinically stable. Therefore, the consensus group accepted and included this recommendation, as it encourages the rational use of antimicrobials, reduces the costs of care and hospital stay and, according to the evidence found, is a safe decision.

Summary of evidence

The evidence identified regarding the route of administration of antimicrobials in patients with moderate to severe CAP has a very low quality. For example, in a literature review, Cassiere & Fein84 report that switching from intravenous to oral administration in low-risk patients was an effective and safe intervention in the treatment of CAP. Likewise, Marras et al.,85 in a meta-analysis that included 7 studies (a total of 1 366 hospitalized adult patients with CAP), concluded that in patients with non-severe CAP who received oral antibiotic treatment, the strategy was effective and therapy lasted 1.3 days less (95%CI: 0.4%-2.2% days; p<0.01) than in the group of patients who received intravenous therapy.

Furthermore, based on the evidence found, the main costs of treating moderate to severe CAP are related to the duration of intravenous antimicrobial therapy and the length of hospital stay, so switching to oral antibiotics significantly reduces the costs of care for these patients, without this change implying harm to the patient or being associated with recurrences of infection and the development of complications.86 Once the patient is clinically stable and the switch from intravenous to oral antibiotics has been made, in-hospital observation is not required, so discharge, if there are no other contraindications, can be immediate, as confirmed by Nathan et al. 87 in their retrospective study carried out with data obtained from the US Medicare National Pneumonia Project. In Colombia, the antimicrobials mentioned in the recommendations are covered by the health benefits plan of the Colombian health system.

Question N° 12. Should antiviral therapy be included in the treatment of adult patients with CAP who test positive for influenza?

Recommendations

  • We recommend initiating influenza treatment (e.g., oseltamivir) in adult patients with severe CAP who test positive for influenza, regardless of the duration of illness prior to diagnosis (strength of recommendation: strong for; quality of evidence: very low ⨁◯◯◯).

Rationale for the recommendation

Evidence on the use of influenza antiviral therapy in the context of CAP is very scarce and has a very low quality. No clinical trial that directly evaluated the usefulness of this type of treatment exclusively in patients diagnosed with CAP was found, but instead evidence comes from observational studies conducted in patients with different types of lower respiratory tract infections describing benefits in reducing the frequency of complications, the duration of symptoms, and the risk of mortality, even when antiviral administration is initiated more than 48 hours after the onset of symptoms. However, these results have not been consistent and have only been reported for patients with severe CAP. Moreover, the benefits of using these drugs have only been described in patients with a positive microbiological test for influenza virus, so the consensus group decided to make this recommendation only in this setting.

Summary of evidence

No clinical trials evaluating the use of oseltamivir in patients with CAP were found; in fact, very few studies were identified, and they have a very low quality with a high risk of bias. For example, Lee et al. 88 reported that for hospitalized patients with confirmed influenza A/B respiratory infection (n=754), the use of antiviral drugs was significantly associated with a reduced risk of mortality (adjusted HR: 0.27, 95%CI: 0.13-0.55; p<0.01) and that early treatment (within 2 days after symptom onset) was associated with faster discontinuation of oxygen therapy (adjusted HR: 1.30, 95%CI: 1.01-1.69; p=0.04) and sooner hospital discharge (adjusted HR: 1.28, 95%CI: 1.04-1.57; p=0.01). McGeer et al.,89 in a study conducted in Toronto involving 512 hospitalized patients with a laboratory-confirmed diagnosis of influenza (185 children, none of whom died), reported that treatment with influenza antiviral drugs was associated with a significant decrease in mortality (OR: 0.21, 95%CI: 0.06-0.80) but that no benefit was observed for other outcomes such as length of hospital stay.

According to some of the initial clinical studies on this subject, such as the one conducted in the United States by Siston et al. 90 with data from 788 pregnant women diagnosed with AH1N1 influenza, antiviral therapy should be initiated within 48 hours of symptom onset.90 However, good results have also been reported when this therapy is started 4 to 5 days after symptom onset.91

Although the usefulness of antiviral therapy has been reported primarily in the in-hospital setting, a reduction in the risk of complications has also been demonstrated in the outpatient setting. This was evidenced in a systematic review and meta-analysis that included 9 clinical trials (4 328 patients) where it was reported that the frequency of lower respiratory tract complications requiring antibiotics at 48 hours was lower in the group that received oseltamivir compared to the placebo group (4.2% vs. 8.7%), estimating a 44% reduction in the risk of these complications with treatment with this antiviral (RR: 0.56, 95%CI:0.42-0.75; p=00001), with an absolute risk difference of -3.8% (95%CI: -5.0 to -2.2).92 Concerning the in-hospital setting, Muthuri et al.,93 in a systematic review including individual data from 29 234 patients infected with H1N1pdm09 influenza virus and hospitalized during the 2009 pandemic, found that, compared with using no antiviral therapy, treatment with neuraminidase inhibitors (regardless of the time of onset) was associated with a reduction in the risk of mortality (adjusted OR: 0.81, 95%CI: 0.70-0.93; p=0.0024). Also, compared to late onset, early initiation of treatment (within the first 2 days after symptom onset) was also significantly associated with a reduction in the risk of mortality (adjusted OR: 0.50, 95%CI: 0.37-0.6; p<0.0001).

The use of oseltamivir and zanamivir (another neuroaminidase inhibitor) for the treatment of influenza has been extensively studied in the outpatient setting; in this regard, it has been reported that although these antiviral drugs mildly reduce symptoms, their use does not have a relevant clinical impact and their effect on reducing the use of antibiotics is low or null.94 Furthermore, a systematic review that included randomized controlled clinical trials conducted in patients with confirmed or suspected exposure to influenza virus reported that, although the use of oseltamivir reduced the time to first symptom relief in adults by 16.8 hours (95%CI: 8.4-25.1 hours; p<0.001), this drug was associated with an increase in the frequency of nausea, vomiting and psychiatric symptoms,95 thus concluding that its use in the outpatient setting is not very beneficial for these patients. In view of the above, the need to use this drug only in patients with a microbiologically confirmed diagnosis of influenza is strongly emphasized.

In Colombia, during the 2009 H1N1 influenza pandemic, the use of oseltamivir was implemented for the treatment of patients with severe acute respiratory infection, so the access to this drug is guaranteed since then in all health centers of the country. This fact makes this recommendation feasible with a limited impact on the costs currently incurred by healthcare centers associated with the care of these patients.96

Question N° 13. Should corticosteroids be used in adult inpatients with CAP?

Recommendations

  • Patients with mild to moderate CAP:

We do not recommend using corticosteroids to treat patients with mild to moderate CAP (strength of recommendation: strong against; quality of evidence: moderate ⨁⨁⨁◯).

  • Patients with severe CAP (Table 1):

We suggest using corticosteroids in patients with severe CAP (strength of recommendation: weak for; quality of evidence: moderate ⨁⨁⨁◯).

Good clinical practice point

  • Provided there are no contraindications, use corticosteroids in patients with COVID-19.

  • Avoid the use of corticosteroids in patients with influenza.

Rationale for the recommendation

No studies were found to support the use of corticosteroids in patients with mild to moderate CAP; however, there is scientific evidence of the benefit of their use in patients with severe CAP in terms of mortality, requirement of mechanical ventilation, and length of stay in the ICU.

Therefore, we suggest using these drugs in these patients taking into account clinical judgment, the absence of contraindications, and the analysis of the balance between risks and benefits, since their use is frequently associated with adverse effects, hyperglycemia being the most common, which could affect the clinical outcome of patients with sepsis of pulmonary origin. Corticosteroids and suggested doses to be used in these patients are presented in Table 5.97,98

Table 5: Corticosteroids for clinical use suggested to treat patients with severe CAP.

Source: Adapted from Samuel et.al 97 and Liu et al. 98

Summary of evidence

Some studies have documented the benefit of using corticosteroids in patients with severe CAP. Confalioniere et al., 99 in a multicenter randomized controlled trial conducted in 46 patients with CAP admitted to the ICU and receiving antibiotic treatment, found that, compared to placebo, the use of hydrocortisone infusion was associated with a significant decrease in hospital stay and mortality. However, it has not been possible to reproduce this considerable reduction in the risk of death of these patients in other studies and even some studies, such as the multicenter, randomized, double-blind, controlled trial conducted by Torres et al. 100 in 120 patients with severe CAP, have described that the use of corticosteroids did not lead to a decrease in hospital stay or mortality.

At first, different meta- analyses, such as the one conducted in 2015 by Chen et al. 101 (7 randomized clinical trials; 944 patients with CAP), documented that the use of these drugs (specifically glucocorticoids) was associated with a decrease in hospital stay, but more recent meta- analyses, such as the one conducted by Jian et al 102 (10 randomized clinical trials; 665 patients), have identified a significant reduction in mortality. In addition, other studies, such as the multicenter double-blind randomized controlled trial conducted by Blum et al.103 in 785 hospitalized adult CAP patients, have documented that the time to reach clinical stability is shorter in patients receiving steroids such as prednisone and that the use of these drugs is also associated with a reduction in the time requiring mechanical ventilation.

The use of steroids has been associated with important adverse effects such as alterations in glucose metabolism (hyperglycemia) and gastrointestinal bleeding. However, the clinical studies reviewed, at the doses and times recommended in this CPG, did not report an increase in the frequency of these events.102 Nevertheless, in the case of patients with pulmonary sepsis, the presence of adverse effects should be routinely evaluated, and appropriate measures should be taken for their prevention and timely control.

On the other hand, the use of steroids is a standard practice for the treatment of patients with COVID-19, so, provided there is no contraindication, these drugs should be used in these patients.9

Finally, according to a recently published meta-analysis that included 21 observational studies, corticosteroid use was associated with increased mortality in patients with influenza (OR: 3.9, 95%CI: 2.3-6.6, 15 studies; adjusted HR: 1.49, 95%CI: 1.09-2.02, 6 studies).104

Implementation and update of the CPG

This CPG should be implemented in health centers that provide health care services to adult patients with CAP in order to support activities related to the treatment of this population and programs to optimize the use of antimicrobial agents. Similarly, the indicators presented in Table 6 should be considered to measure the progress of the guideline's implementation, with the frequency and reporting requirements that each institution deems pertinent.

Table 6: Indicators for measuring the implementation of the clinical practice guideline.

Source: Own elaboration.

In order to facilitate the implementation of this CPG, the following dissemination tools will be used to provide the country's health professionals with better access to its contents: publication of the guideline in the Revista de la Facultad de Medicina of the Universidad Nacional de Colombia and on the website of the Asociación Colombiana de Infectología, as well as inclusion of the guideline recommendations in the contents of a massive open online course (MOOC) and a mobile application for CAP management.

Finally, it is considered that this CPG should be updated within a period no longer than 5 years, following the same methodology and rigor that was used for its development. The topics to be addressed may be reconsidered depending on the needs arising from clinical practice or the appearance of new evidence that should be included in the CPG.

Acknowledgments

Patient representatives: José Ernesto Mosquera and Mildred Pérez, Asociación de Usuarios de Méderi.

Administrative support: Fabiam Andrés Ariza, Faculty of Medicine, Universidad Nacional de Colombia.

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84. Cassiere HA, Fein AM. Duration and route of antibiotic therapy in community-acquired pneumonia: switch and step-down therapy. Semin Respir Infect. 1998;13(1):36-42.

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Cortés JA, Cuervo-Maldonado SI, Nocua-Báez LC, Valderrama MC, Sánchez EA, Saavedra A, et al. Clinical practice guideline for the management of community-acquired pneumonia. Rev. Fac. Med. 2022;70(2):e93814. English. doi: https://doi.org/10.15446/revfacmed.v70n2.93814.
This guideline was prepared within the framework of the project Programas de administración de antimicrobianos en un país latinoamericano (Antimicrobial stewardship programs in a Latin American country) of the Universidad Nacional de Colombia, whose objectives included the elaboration of a CPG for CAP management in the Colombian context. The project was financed by a grant from the International Society for Infectious Diseases (ISID) and Pfizer.
The contents of this guideline were freely developed; there was no influence from ISID and/or Pfizer. All the steps considered in the methodology for the development of this guideline, from the creation of the GDG to the elaboration of the recommendations and writing of the final document, were carried out in their entirety and independently by the development group. The sponsors did not participate in any part of this process, nor did they have any influence over the contents of this document.

Supplementary material

Supplementary Table 1: Medline search strategy.

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Cómo citar

APA

Cortés, J. A., Cuervo-Maldonado, S. I., Nocua-Báez, L. C., Valderrama, M. C., Sánchez, E. A., Saavedra, A., Torres, J. V., Forero, D. P., Álvarez-Moreno, C. A., Leal, A. L., Pérez, J. E., Rodríguez, I. A., Guevara, F. O., Saavedra, C. H., Vergara, E. P., Montúfar, F. E., Espinosa, T., Chaves, W., Carrizosa, J. A., Meléndez, S. D. M., Espinosa, C. J., García-López, F., Guzmán, I. J., Cortés, S. L., Díaz, J. A. y González, N. (2022). Clinical Practice Guideline for the management of community-acquired pneumonia. Revista de la Facultad de Medicina, 70(2), e93814. https://doi.org/10.15446/revfacmed.v70n2.93814

ACM

[1]
Cortés, J.A., Cuervo-Maldonado, S.I., Nocua-Báez, L.C., Valderrama, M.C., Sánchez, E.A., Saavedra, A., Torres, J.V., Forero, D.P., Álvarez-Moreno, C.A., Leal, A.L., Pérez, J.E., Rodríguez, I.A., Guevara, F.O., Saavedra, C.H., Vergara, E.P., Montúfar, F.E., Espinosa, T., Chaves, W., Carrizosa, J.A., Meléndez, S.D.M., Espinosa, C.J., García-López, F., Guzmán, I.J., Cortés, S.L., Díaz, J.A. y González, N. 2022. Clinical Practice Guideline for the management of community-acquired pneumonia. Revista de la Facultad de Medicina. 70, 2 (abr. 2022), e93814. DOI:https://doi.org/10.15446/revfacmed.v70n2.93814.

ACS

(1)
Cortés, J. A.; Cuervo-Maldonado, S. I.; Nocua-Báez, L. C.; Valderrama, M. C.; Sánchez, E. A.; Saavedra, A.; Torres, J. V.; Forero, D. P.; Álvarez-Moreno, C. A.; Leal, A. L.; Pérez, J. E.; Rodríguez, I. A.; Guevara, F. O.; Saavedra, C. H.; Vergara, E. P.; Montúfar, F. E.; Espinosa, T.; Chaves, W.; Carrizosa, J. A.; Meléndez, S. D. M.; Espinosa, C. J.; García-López, F.; Guzmán, I. J.; Cortés, S. L.; Díaz, J. A.; González, N. Clinical Practice Guideline for the management of community-acquired pneumonia. Rev. Fac. Med. 2022, 70, e93814.

ABNT

CORTÉS, J. A.; CUERVO-MALDONADO, S. I.; NOCUA-BÁEZ, L. C.; VALDERRAMA, M. C.; SÁNCHEZ, E. A.; SAAVEDRA, A.; TORRES, J. V.; FORERO, D. P.; ÁLVAREZ-MORENO, C. A.; LEAL, A. L.; PÉREZ, J. E.; RODRÍGUEZ, I. A.; GUEVARA, F. O.; SAAVEDRA, C. H.; VERGARA, E. P.; MONTÚFAR, F. E.; ESPINOSA, T.; CHAVES, W.; CARRIZOSA, J. A.; MELÉNDEZ, S. D. M.; ESPINOSA, C. J.; GARCÍA-LÓPEZ, F.; GUZMÁN, I. J.; CORTÉS, S. L.; DÍAZ, J. A.; GONZÁLEZ, N. Clinical Practice Guideline for the management of community-acquired pneumonia. Revista de la Facultad de Medicina, [S. l.], v. 70, n. 2, p. e93814, 2022. DOI: 10.15446/revfacmed.v70n2.93814. Disponível em: https://revistas.unal.edu.co/index.php/revfacmed/article/view/93814. Acesso em: 6 feb. 2025.

Chicago

Cortés, Jorge Alberto, Sonia Isabel Cuervo-Maldonado, Laura Cristina Nocua-Báez, Martha Carolina Valderrama, Edgar Alberto Sánchez, Alfredo Saavedra, July Vianneth Torres, Diana Paola Forero, Carlos Arturo Álvarez-Moreno, Aura Lucía Leal, Jairo Enrique Pérez, Iván Arturo Rodríguez, Fredy Orlando Guevara, Carlos Humberto Saavedra, Erika Paola Vergara, Franco Eduardo Montúfar, Tatiana Espinosa, Walter Chaves, Jorge Armando Carrizosa, Sugeich Del Mar Meléndez, Carmelo José Espinosa, Felipe García-López, Ingrid Jany Guzmán, Sergio Leonardo Cortés, Jorge Augusto Díaz, y Nathaly González. 2022. «Clinical Practice Guideline for the management of community-acquired pneumonia». Revista De La Facultad De Medicina 70 (2):e93814. https://doi.org/10.15446/revfacmed.v70n2.93814.

Harvard

Cortés, J. A., Cuervo-Maldonado, S. I., Nocua-Báez, L. C., Valderrama, M. C., Sánchez, E. A., Saavedra, A., Torres, J. V., Forero, D. P., Álvarez-Moreno, C. A., Leal, A. L., Pérez, J. E., Rodríguez, I. A., Guevara, F. O., Saavedra, C. H., Vergara, E. P., Montúfar, F. E., Espinosa, T., Chaves, W., Carrizosa, J. A., Meléndez, S. D. M., Espinosa, C. J., García-López, F., Guzmán, I. J., Cortés, S. L., Díaz, J. A. y González, N. (2022) «Clinical Practice Guideline for the management of community-acquired pneumonia», Revista de la Facultad de Medicina, 70(2), p. e93814. doi: 10.15446/revfacmed.v70n2.93814.

IEEE

[1]
J. A. Cortés, «Clinical Practice Guideline for the management of community-acquired pneumonia», Rev. Fac. Med., vol. 70, n.º 2, p. e93814, abr. 2022.

MLA

Cortés, J. A., S. I. Cuervo-Maldonado, L. C. Nocua-Báez, M. C. Valderrama, E. A. Sánchez, A. Saavedra, J. V. Torres, D. P. Forero, C. A. Álvarez-Moreno, A. L. Leal, J. E. Pérez, I. A. Rodríguez, F. O. Guevara, C. H. Saavedra, E. P. Vergara, F. E. Montúfar, T. Espinosa, W. Chaves, J. A. Carrizosa, S. D. M. Meléndez, C. J. Espinosa, F. García-López, I. J. Guzmán, S. L. Cortés, J. A. Díaz, y N. González. «Clinical Practice Guideline for the management of community-acquired pneumonia». Revista de la Facultad de Medicina, vol. 70, n.º 2, abril de 2022, p. e93814, doi:10.15446/revfacmed.v70n2.93814.

Turabian

Cortés, Jorge Alberto, Sonia Isabel Cuervo-Maldonado, Laura Cristina Nocua-Báez, Martha Carolina Valderrama, Edgar Alberto Sánchez, Alfredo Saavedra, July Vianneth Torres, Diana Paola Forero, Carlos Arturo Álvarez-Moreno, Aura Lucía Leal, Jairo Enrique Pérez, Iván Arturo Rodríguez, Fredy Orlando Guevara, Carlos Humberto Saavedra, Erika Paola Vergara, Franco Eduardo Montúfar, Tatiana Espinosa, Walter Chaves, Jorge Armando Carrizosa, Sugeich Del Mar Meléndez, Carmelo José Espinosa, Felipe García-López, Ingrid Jany Guzmán, Sergio Leonardo Cortés, Jorge Augusto Díaz, y Nathaly González. «Clinical Practice Guideline for the management of community-acquired pneumonia». Revista de la Facultad de Medicina 70, no. 2 (abril 1, 2022): e93814. Accedido febrero 6, 2025. https://revistas.unal.edu.co/index.php/revfacmed/article/view/93814.

Vancouver

1.
Cortés JA, Cuervo-Maldonado SI, Nocua-Báez LC, Valderrama MC, Sánchez EA, Saavedra A, Torres JV, Forero DP, Álvarez-Moreno CA, Leal AL, Pérez JE, Rodríguez IA, Guevara FO, Saavedra CH, Vergara EP, Montúfar FE, Espinosa T, Chaves W, Carrizosa JA, Meléndez SDM, Espinosa CJ, García-López F, Guzmán IJ, Cortés SL, Díaz JA, González N. Clinical Practice Guideline for the management of community-acquired pneumonia. Rev. Fac. Med. [Internet]. 1 de abril de 2022 [citado 6 de febrero de 2025];70(2):e93814. Disponible en: https://revistas.unal.edu.co/index.php/revfacmed/article/view/93814

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1. Pablo Restrepo Maya, Santiago Vargas Pardo. (2024). Enfoque del paciente con neumonía adquirida en la comunidad. https://doi.org/10.59473/medudea.pc.2024.83.

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