Efficacy and safety of 24 antibiotics for group A streptococcal pharyngitis: a network meta-analysis of 64 randomized controlled trials.

BACKGROUND AND AIMS: Penicillin remains the first-line therapy for group A streptococcal (GAS) pharyngitis. However, broad-spectrum antibiotics continue to be widely prescribed in clinical practice. This study aimed to evaluate the relative efficacy and safety profiles of antibiotics for GAS pharyngitis.

METHODS

Literature published through March 2026 was searched. Efficacy outcomes included early and late bacterial eradication, clinical response, and bacteriological recurrence, whereas safety was assessed according to adverse events. Per-protocol data were extracted, and a Bayesian network meta-analysis was performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs).

RESULTS

We identified 64 RCTs (23,287 participants). For early bacterial eradication, cefdinir (OR: 3.09; 95% CI: 1.60-6.01) and cefpodoxime proxetil (OR: 2.58; 95% CI: 1.07-6.17) demonstrated greater efficacy compared with penicillin V, whereas azithromycin showed inferior eradication rates than penicillin V (OR: 0.53; 95% CI: 0.32-0.90). For late bacterial eradication, cefprozil demonstrated greater efficacy compared with penicillin V (OR: 3.12; 95% CI: 1.03-11.25), whereas azithromycin exhibited suboptimal performance (OR: 0.38; 95% CI: 0.25-0.62). For early clinical response, cefdinir (OR: 2.01; 95% CI: 1.28-3.25) and cefuroxime axetil (OR: 2.14; 95% CI: 1.19-3.60) demonstrated significantly greater efficacy compared with penicillin V. For late clinical response, spiramycin showed superior efficacy to penicillin V (OR: 0.17; 95% CI: 0.02-0.94), although evidence was limited to a single small trial. Azithromycin was associated with reduced efficacy, higher late recurrence rates, and increased adverse events.

CONCLUSION

Standard penicillins should remain the preferred first-line therapy for GAS pharyngitis to support antimicrobial stewardship. Cefdinir represents an effective alternative. Conversely, azithromycin should be avoided due to inferior efficacy and increased adverse risks.

SYSTEMATIC REVIEW REGISTRATION: http://www.crd.york.ac.uk/prospero, identifier CRD420251104703.