Investigating a possible link between antiseptic treatment and the increased occurrence of daptomycin-resistant Staphylococcus aureus

Abstract

Objectives: Because of a steady increase in the detection of daptomycin-resistant (DAP-R) Staphylococcus aureus at three medical centres in Cologne, Germany, molecular surveillance was established from June 2016 to June 2018 to investigate the causes of the emergence and spread of respective isolates. Seventy-five S. aureus isolates, both DAP-R and DAP-susceptible, were collected from 42 patients for further analysis. Methods: Broth microdilution was used to determine the MICs for 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. Epidemiological, clinical, microbiological and molecular data were analysed comparatively. Results: Acquisition of DAP resistance was mainly observed in patients with acute and chronic wounds (40/42, 96.2%) treated with antiseptic (32/42, 76.2%) rather than systemic antibiotic therapy using DAP or vancomycin (7/42, 16.7%). 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 (50/54, 92.6%), and in vitro selection experiments confirmed that PHMB treatment is capable of generating DAP resistance. DAP resistance could be linked to 12 different polymorphisms in the mprF gene in the majority of clinical isolates (52/54, 96.3%) as well as in all in vitro selected strains. Discussion: 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.