Increase of daptomycin-resistant Staphylococcus aureus with a possible link to antiseptic wound treatment

Objectives: Due to a steady increase in the detection of daptomycin-resistant (DAP-R) Staphylococcus aureus (S. aureus) at three medical centres molecular surveillance was. Seventy-five S. aureus isolates, both DAP-R and daptomycin-susceptible (DAP-S), were collected from forty-two patients for further analysis. Methods: Broth-microdilution was used to determine the MICs for daptomycin (DAP) and polyhexamethylene biguanide/polyhexanide (PHMB). To investigate the effect of PHMB on the development of DAP resistance, we performed selection experiments with PHMB. All isolates studied were subjected to whole genome sequencing (WGS). Epidemiological, clinical, microbiological and molecular data were analysed comparatively. Results: Acquisition of DAP resistance was mainly observed in patients suffering from chronic wounds treated with antiseptic rather than systemic antibiotic therapy. DAP-R S. aureus had a diverse genetic background; however, within individual patients, isolates were closely related. At least three potential transmission events were detected. Most DAP-R isolates had concomitant elevated MICs for PHMB, and in vitro selection experiments confirmed that PHMB is capable of generating DAP resistance. DAP resistance could be linked to different polymorphisms in the mprF gene in the majority of clinical isolates as well as in the in vitro selected strains. Conclusions: DAP resistance in S. aureus can occur independently of prior antibiotic therapy and can be selected by PHMB. Therefore, wound treatment with PHMB may trigger individual resistance development associated with gain-of-function mutations in the mprF gene.