Impact of exposure of methicillin-resistant Staphylococcus aureus to polyhexanide in vitro and in vivo.

Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increase the need to develop alternative decolonization molecules. The absence of reported adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as topical antiseptic. In the present study we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced-susceptibility to polyhexanide by prolonged-stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes, and with concomitant decreased susceptibility to daptomycin and other cell-wall active antibiotics. However, the in vitro emergence of reduced-susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine antiseptic. During in vivo polyhexanide clinical decolonization treatment, neither polyhexanide reduced-susceptibility nor chlorhexidine cross-resistance were observed. Together, these observations suggest that polyhexanide could be used safely for decolonisation of carriers of chlorhexidine-resistant S. aureus strains but highlight the need for careful use of polyhexanide at low antiseptic concentrations.