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

Ghadimi M.; Siemieniuk R.A.C.; Loeb M.; Lima J.P.; Aminaei D.; Gomaa H.; Wang Y.; Hazzan A.A.; Basmaji J.; Yao L.; Kim W.S.H.; Grant A.; Agarwal A.; Motaghi S.; Tajika A.; Takayama T.; Alvarado-Gamarra G.; Kirmayr K.; Muti Schuenemann G.E.U.; Zandieh S.; Das A.; Manja V.; Momenilandi F.; Likhvantsev V.; Couban R.; Sadeghirad B.; Brignardello-Petersen R.; Guyatt G. · Clinical Microbiology and Infection (2025) · DOI: 10.1016/j.cmi.2025.06.033

Resumen

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).