Empiric antibiotic therapy for moderate to severe community-acquired pneumonia: a systematic review and network meta-analysis.
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BACKGROUND: The optimal empiric antibiotic regimen for moderate to severe community-acquired pneumonia (CAP) is uncertain. OBJECTIVES: To compare the effects of antibiotics for empiric therapy of moderate to severe CAP using a network meta-analysis (NMA). DATA SOURCES: Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from inception to July 03, 2024. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCT). PARTICIPANTS: Adults with moderate to severe CAP. INTERVENTIONS: Any empiric antibiotic regimen versus another, placebo, or no treatment. ASSESSMENT OF RISK OF BIAS: Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials. METHODS OF DATA SYNTHESIS: We conducted frequentist random-effects NMAs addressing patient-important outcomes and assessed the certainty of evidence using the GRADE approach. RESULTS: 143 RCTs involving 29,157 participants proved eligible. Effects are in comparison with respiratory fluoroquinolones alone. Penicillins alone (RR 1.25, 95% CI 0.93 to 1.67; RD 33 more per 1000, 95% CI 9 fewer to 88 more), 2nd generation cephalosporins alone (RR 1.34, 95% CI 0.89 to 2.02; RD 45 more per 1000, 95% CI 15 fewer to 135 more), and 3rd generation cephalosporins alone (RR 1.32, 95% CI 0.99 to 1.77; RD 42 more per 1000, 95% CI 1 fewer to 102 more) or combined with a macrolide (RR 1.34, 95% CI 0.98 to 1.84; RD 45 more per 1000, 95% CI 3 fewer to 111 more) may be inferior in reducing treatment failure (all low certainty). The evidence among other antibiotic regimens for treatment failure and among all regimens for all-cause mortality, duration of hospitalization, and adverse events suggested little to no difference (in most cases with low certainty) or was very low certainty. CONCLUSIONS: For empiric treatment of moderate to severe CAP, none of the antibiotic regimens provided convincing evidence of important differences in any of the outcomes. REGISTRATION: PROSPERO (CRD42022297216).
