Known mechanisms account for less than half of antimicrobial resistance in a diverse collection of non-aureus staphylococci.
Introduction: Non-aureus staphylococci (NAS) are implicated in many healthcare-acquired infections and an understanding of the genetics of antimicrobial resistance in NAS is important in relation to both clinical intervention and the role of NAS as a reservoir of resistance genes. Gap statement: The burden of antimicrobial resistance in NAS, particularly to clinically relevant antimicrobials, is understudied. Methodology: We sourced 394 NAS isolates from clinical samples, healthy human volunteers, animals and type cultures and subjected them to agar dilution susceptibility testing against eight antimicrobials. We performed whole genome sequencing on 316 isolates and analysed these genotypically for the presence of genetic mechanisms responsible for the phenotypic levels of reduced antimicrobial susceptibility. Results: Cefoxitin is used to screen for methicillin resistance in S. aureus, as it stimulates expression of mecA. We observed 174 isolates with an MIC of at least 4 μg/ml to cefoxitin, of which sequencing revealed 47.6% (80/168) did not harbour a known mec homologue. Seven clinical NAS isolates displayed high daptomycin minimum inhibitory concentrations (MICs) (>4 μg/ml), with no known mechanism identified. Differences in MICs against erythromycin were attributable to the presence of different resistance genes (msrA and ermC). In total, 49% (187/394) of isolates displayed reduced susceptibility to three or more of the antimicrobials tested. Conclusions: The widespread presence of reduced antimicrobial susceptibility in NAS is a concern, with an increased likelihood of (1) harder to treat infections caused directly by NAS, and (2) resistance genes being passed on to other bacteria via horizontal gene transfer, both of which have clinical implications for treatment and management of patients.