Empiric antibiotic therapy for moderate-to-severe community-acquired pneumonia: a systematic review and network meta-analysis

Abstract

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.

Data sources: Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from inception to 03 July 2024.

Study eligibility criteria: Randomized controlled trials (RCT).

Participants: Adults with moderate-to-severe CAP.

Interventions: Any empiric antibiotic regimen vs. 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-effect network meta-analyses addressing patient-important outcomes and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results: In total, 143 RCTs involving 29,157 participants proved eligible. Effects are in comparison with respiratory fluoroquinolones alone. Penicillins alone (relative risks [RR]: 1.25, 95% CI: 0.93-1.67; risk difference [RD]: 33 more per 1000, 95% CI: 9 fewer to 88 more), second-generation cephalosporins alone (RR: 1.34, 95% CI: 0.89-2.02; RD: 45 more per 1000, 95% CI: 15 fewer to 135 more), and third-generation cephalosporins alone (RR: 1.32, 95% CI: 0.99-1.77; RD: 42 more per 1000, 95% CI: 1 fewer to 102 more) or combined with a macrolide (RR: 1.34, 95% CI: 0.98-1.84; 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.

Trial registration number: PROSPERO (CRD42022297216).

Keywords: Adverse events; All-cause mortality; Community-acquired pneumonia; Empiric antibiotic therapy; Moderate-to-severe; Network meta-analysis; Systematic review; Treatment failure.