Abstract
Highly variable resistance rates to erythromycin and clindamycin have been reported in the β-hemolytic streptococcal species Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus dysgalactiae, depending on geographic and temporal context. In the present study we aimed to examine the longitudinal trends of antimicrobial resistance in these three species in a northern European setting. Furthermore, we used whole genome sequencing to identify resistance determinants and the mobile genetic elements involved in their dissemination, as well as elucidate phylogenetic relationships. All cases of invasive β-hemolytic streptococcal diseases in Health Region Bergen, western Norway, in the period 2004 to 2018 were retrospectively identified, comprising 271, 358, and 280 cases of S. pyogenes, S. agalactiae, and S. dysgalactiae, respectively. Antimicrobial susceptibility testing revealed a gradual but significant increase in erythromycin and clindamycin resistance for S. agalactiae and S. dysgalactiae during the study period. Whole genome sequencing of the erythromycin and clindamycin resistant bacterial population revealed a substantial phylogenetic diversity in S. agalactiae and S. dysgalactiae. However, the mobile genetic elements harboring the resistance determinants showed remarkable intra- and interspecies similarities, suggesting a dissemination of antimicrobial resistance predominantly through conjugative transfer rather than clonal expansion of resistant strains in these two species. Conversely, antimicrobial resistance in S. pyogenes remained low, apart from a transient outbreak of a clindamycin and erythromycin resistant emm11/ST403-clone in 2010–2012. Increased epidemiological attentiveness is warranted to monitor the emerging threat of antimicrobial resistance in β-hemolytic streptococci, particularly in S. agalactiae and S. dysgalactiae.
Highlights
The major human pathogens among β-hemolytic streptococci (BHS) are Streptococcus pyogenes (Lancefield group A streptococcus, GAS), Streptococcus agalactiae (Lancefield group B streptococcus, GBS), and Streptococcus dysgalactiae (Lancefield group C and G streptococcus, SD).These phylogenetically closely related species produce overlapping clinical manifestations, and explore phylogenetic relationships and clonality in the resistant bacterial population.collectively they are responsible for substantial global disease burden (Carapetis et al, 2005; Le Doare and Heath, 2013; Rantala, 2014)
We identified a total of 995 culture positive cases of invasive
We have conducted a comprehensive analysis of macrolide and clindamycin resistance in invasive BHS isolates over a 15-year period, and to the best of our knowledge, this is the first study investigating the temporal trends of such resistance in SD isolates
Summary
The major human pathogens among β-hemolytic streptococci (BHS) are Streptococcus pyogenes (Lancefield group A streptococcus, GAS), Streptococcus agalactiae (Lancefield group B streptococcus, GBS), and Streptococcus dysgalactiae (Lancefield group C and G streptococcus, SD).These phylogenetically closely related species produce overlapping clinical manifestations, and explore phylogenetic relationships and clonality in the resistant bacterial population.collectively they are responsible for substantial global disease burden (Carapetis et al, 2005; Le Doare and Heath, 2013; Rantala, 2014). The major human pathogens among β-hemolytic streptococci (BHS) are Streptococcus pyogenes (Lancefield group A streptococcus, GAS), Streptococcus agalactiae (Lancefield group B streptococcus, GBS), and Streptococcus dysgalactiae (Lancefield group C and G streptococcus, SD). These phylogenetically closely related species produce overlapping clinical manifestations, and explore phylogenetic relationships and clonality in the resistant bacterial population. In GAS and GBS, all these resistance genes are associated with mobile genetic elements, and dissemination of these elements occur by either clonal expansion or horizontal genetic transfer (Varaldo et al, 2009; Palmieri et al, 2013; Hawkins et al, 2017; Zhou et al, 2017). In vitro conjugal transfer of integrative conjugative elements (ICEs) harboring resistance genes has been demonstrated between these three species, and a common reservoir for resistance determinants is feasible (Palmieri et al, 2013)
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