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

Why clinicians should know about it

• Picked for Microbiology (medical) (top studies of the week, 19 July 2026).

Abstract

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.

Abstract as published, via PubMed.