Initial antibiotic treatment for coverage of 'atypical' pathogens for community-acquired pneumonia in hospitalized adults

Robenshtok E, Shefet D, Gafter-Gvili A, Paul M, Vidal L, Leibovici L

Published Online:

October 6, 2010

Agents which cause pneumonia are traditionally divided into 'typical' and 'atypical', each dictating a distinct antibiotic treatment. Atypical agents refer to certain bacteria - namely, Legionella pneumophila (L. pneumophila), Mycoplasma pneumoniae (M. pneumoniae), and Chlamydia pneumoniae (C. pneumoniae). At presentation the causative agent is usually unknown so the initial treatment is empirical, customarily covering both groups. While typical coverage is essential, due to the common 'typical' pathogen Streptococcus pneumoniae (S. pneumoniae), the necessity of the atypical coverage has not been proven. This study reviewed trials comparing antibiotic regimens with atypical coverage to those without, limited to hospitalized adults with community-acquired pneumonia. Twenty five trials were included, encompassing 5244 patients. For the regimens tested, no advantage was found for regimens covering atypical pathogens in the major outcomes tested - clinical efficacy or mortality.

Abstract (click to read)

Background:

Community acquired pneumonia (CAP) is caused by various pathogens, traditionally divided into 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense.

Objectives:

To assess the efficacy and need of adding antibiotic coverage for atypical pathogens in hospitalized patients with CAP, in terms of mortality and successful treatment.

Search strategy:

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 1) which includes the Acute Respiratory Infection Group's specialized register; MEDLINE (January 1966 to March 2007); and EMBASE (January 1980 to January 2007).

Selection criteria:

Randomized trials of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical antibiotic coverage to a regimen without atypical antibiotic coverage.

Data collection and analysis:

Two review authors independently appraised the quality of each trial and extracted the data from included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated, assuming an intention-to-treat (ITT) basis for the outcome measures.

Main results:

Twenty five trials were included, encompassing 5244 randomized patients. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.15; 95% CI 0.85 to 1.56). The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high-quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non-significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were more common in the non-atypical arm (RR 0.73, 95% CI 0.54 to 0.99). All but two included trials compared a single atypical antibiotic to a beta-lactam, while no trials assessing the addition of an atypical antibiotic to a beta-lactam were identified.

Authors' conclusions:

No benefit of survival or clinical efficacy was shown to empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams (BL) or cephalosporins. Further trials, comparing BL or cephalosporins therapy to BL or cephalosporins combined with a macrolide in this population, using mortality as its primary outcome, should be performed.

This record should be cited as:

Robenshtok E, Shefet D, Gafter-Gvili A, Paul M, Vidal L, Leibovici L. Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD004418. DOI: 10.1002/14651858.CD004418.pub3

Assessed as up to date:

November 1, 2007

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Primary Review Group:

Acute Respiratory Infections Group

Health topics:

Infectious disease > Respiratory infections > Pneumonia

Lungs & airways > Respiratory infections > Pneumonia

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Independent high-quality evidence for health care decision making

Initial antibiotic treatment for coverage of 'atypical' pathogens for community-acquired pneumonia in hospitalized adults

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