Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults
E Robenshtok1, D Shefet, A Gafter-Gvili
1Campus Beilinson, Dept of Medicine E, Rabin Medical Center, Petah-Tikva, Israel, 49100. robensht@netvision.net.il
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:
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.
Insights
Adding atypical pathogen coverage to community-acquired pneumonia (CAP) antibiotics showed no survival benefit. This empirical approach did not improve mortality or clinical success in hospitalized patients.
Area of Science:
- Infectious Diseases
- Pharmacology
- Clinical Medicine
Background:
- Community-acquired pneumonia (CAP) is often treated empirically with antibiotics targeting both typical and atypical pathogens.
- Evidence supporting broad-spectrum coverage for CAP is limited, while narrower coverage could reduce adverse effects and costs.
Purpose of the Study:
- To evaluate the efficacy and necessity of including atypical pathogen coverage in antibiotic regimens for hospitalized CAP patients.
- Primary outcomes assessed were mortality and treatment success.
Main Methods:
- A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted.
- Searches included Cochrane CENTRAL, MEDLINE, and EMBASE databases.
- Twenty-five RCTs involving 5244 patients were analyzed, comparing atypical coverage versus no atypical coverage.
Main Results:
- No significant difference in mortality was observed between groups (RR 1.15; 95% CI 0.85 to 1.56).
- Atypical coverage showed a trend toward clinical success and improved bacterial eradication, but this was not significant in high-quality studies.
- Gastrointestinal events were more frequent in the non-atypical arm.
Conclusions:
- Empirical atypical coverage in hospitalized CAP patients does not demonstrate benefits in survival or clinical efficacy.
- Current evidence primarily compares monotherapy with atypical agents to beta-lactams.
- Further trials are needed to assess the combination of beta-lactams/cephalosporins with macrolides, using mortality as the primary endpoint.
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