Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults.

BACKGROUND: Community acquired pneumonia (CAP) is caused by various pathogens, traditionally divided to '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: 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 Issue 1, 2005) which includes the Acute Respiratory Infection Group's specialized register; MEDLINE (January 1966 to January Week 2 2005); and EMBASE (January 1980 to January Week 2 2005). 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 reviewers 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 four trials were included, encompassing 5015 randomized patients. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.13; 95% CI 0.82 to 1.54). 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). 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 non-atypical monotherapy. Further trials, comparing beta-lactam (BL) or cephalosporin therapy to BL or cephalosporin combined with a macrolide in this population, using mortality as its primary outcome, should be performed.