Large-scale global molecular epidemiology of antibiotic resistance determinants in Streptococcus pneumoniae.

Abstract

Streptococcus pneumoniae is a leading pathogen in terms of deaths attributable to or associated with antimicrobial resistance globally. Thus, monitoring antibiotic resistance determinants constitutes a key aspect of surveillance efforts for this microbe. Leveraging publicly available whole-genome sequencing (WGS) data, we aimed to investigate the presence and distribution patterns of antibiotic resistance determinants in S. pneumoniae with a focus on multidrug resistance (MDR) and serotype distribution. Metadata and genomes were obtained from the National Center for Biotechnology Information Pathogen Detection database. Curation and harmonization were performed in R and SPSS. Data on resistance patterns were defined according to AMRFinderPlus, and a combination of prediction tools was employed for in silico serotyping. Analyses involved 75,161 genomes totalling 122,673 gene/allele counts from 14 antibiotic classes. MDR was observed in 16.7% of isolates, with the highest increasing rates in Asia and South America. Within antibiotic classes, an increase in macrolide resistance genes was highlighted, particularly in the proportion of genomes presenting mef(A)/msr(D). Over a third of isolates with serotypes 19F, 23F, 15A, 6B and 19A showed MDR. We further observed the highest significant increases in the presence of resistance in 33F, 22F, 10A and 23A. Serotype 13, not included in any vaccine formulation, presented high MDR rates with a strong increasing trend. The findings of this study highlight variations in resistance determinants globally and across serotypes over time. Collectively, these data underscore the added value of utilizing public WGS data to investigate the effectiveness and repercussions of treatment and vaccination strategies on managing antibiotic resistance.