Known mechanisms cannot account for at least one third of reduced susceptibility in a diverse collection of non-aureusstaphylococci

AbstractIntroductionNon-aureusstaphylococci (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 statementThe burden of antimicrobial resistance in NAS, particularly to clinically relevant antimicrobials, is under recognised.MethodologyWe 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. Cefoxitin was used to screen for methicillin resistance inS. aureus, as it stimulates expression ofmecA. We performed whole genome sequencing on 366 isolates and analysed these genotypically for the presence of genetic mechanisms responsible for the phenotypic levels of reduced antimicrobial susceptibility.ResultsWe observed 175 sequenced isolates with a minimum inhibitory concentration (MIC) of at least 4 μg/ml to cefoxitin, of which 50% (87/175) did not harbour a knownmechomologue. Eight clinical NAS isolates displayed high daptomycin MICs (>4 μg/ml), with no known mechanism identified. Differences in MICs against erythromycin were attributable to the presence of different resistance genes (msrAandermC). In total, 49% (193 /394) of isolates displayed reduced susceptibility to three or more of the antimicrobials tested.ConclusionsThe 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.