Abstract
OBJECTIVES: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are potential sequelae of untreated group A streptococcal (Strep A) infections. Guidelines focus on treating Strep A pharyngitis but seldom on skin infections. This systematic review explored whether directed antibiotic therapy for superficial Strep A skin infections prevents ARF/RHD. METHODS: We searched PubMed, Scopus, Cochrane Library, and clinical trial registries for published and ongoing trials measuring the eradication of Strep A and clinical resolution of polymicrobial infections with antibiotics through December 13, 2024. We calculated risk ratios and absolute risk differences, using the grading of recommendations, assessment, development, and evaluation (GRADE) to assess the certainty of evidence. RESULTS: No trials were reported on ARF/RHD outcomes. However, we identified 12 trials and pooled data comparing penicillin, cotrimoxazole, macrolides, and cephalosporins. There was probably no difference between interventions for eradicating Strep A (very low certainty evidence). For clinical resolution, cotrimoxazole was comparable to intramuscular benzathine benzylpenicillin and macrolides to penicillin (moderate certainty evidence). First- and second-generation cephalosporins showed no difference (low certainty evidence), whereas third-generation cephalosporins demonstrated improved clinical response (moderate certainty evidence). Benzathine benzylpenicillin-associated injection-site pain and oral antibiotic-associated gastrointestinal disorders were commonly reported. CONCLUSIONS: The available evidence for directed treatment of Strep A skin infections to prevent ARF/RHD is uncertain, requiring further research, with consideration of antimicrobial resistance and the limited antibiotic pipeline.