Global trends in macrolide and lincosamide resistance in Streptococcus species: a comprehensive systematic review and meta-analysis

Abstract Background The widespread use of macrolides and lincosamides, particularly for treating infections caused by Streptococcus pyogenes (S. pyogenes) (group A Streptococcus (GAS)), and S. pneumoniae has led to a concerning rise in antibiotic resistance. This meta-analysis aimed to evaluate the weighted pooled resistance rates of macrolides and lincosamides in clinical isolates of S. pneumoniae, S. pyogenes, and S. agalactiae (group B Streptococcus (GBS)) based on time, geographical areas, antimicrobial susceptibility testing, and guidelines. Method We systematically searched PubMed, Embase, Web of Science, and Scopus for studies published between 2015 and 2023. Study quality was assessed via the Joanna Briggs Institute Checklist. Resistance rates were calculated with a random-effects model, supplemented by meta-regression, subgroup analyses, and identification of outliers. Statistical analyses were performed in R using the metafor package. Results This review analyzed 276 studies across 62 countries. Pooled resistance was highest for clarithromycin (57.6%) and azithromycin (55.8%), followed by erythromycin (41.5%) and clindamycin (29.5%), all with substantial heterogeneity (I 2 > 98%, p < 0.001). Resistance differed significantly across various countries and continents (p < 0.001). Resistance patterns varied notably by species, with S. pneumoniae exhibiting the highest resistance to all tested macrolides and lincosamides, followed closely by S. agalactiae. In contrast, S. pyogenes consistently showed the lowest resistance levels across all antibiotics examined. A significant upward trend in resistance was observed over time for erythromycin (p = 0.019) and clindamycin (p = 0.003). According to the meta-regression, the erythromycin resistance rate increased over time (r = 0.094, p = 0.005). Conclusion Macrolide and lincosamide resistance among key Streptococcus species are alarmingly high and rising globally, with marked species-specific and regional differences. Our findings underscore the urgent need for standardized susceptibility testing protocols, targeted surveillance by species, and enhanced antibiotic stewardship efforts.