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Impact of Exposure of Methicillin-Resistant Staphylococcus aureus to Polyhexanide In Vitro and In Vivo
A Renzoni1, E Von Dach2, C Landelle3
1Service of Infectious Diseases, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increases the need for development of alternative decolonization molecules. The absence of reported severe adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as a 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. During in vivo polyhexanide clinical decolonization treatment, neither reduced polyhexanide susceptibility nor chlorhexidine cross-resistance was observed. Together, these observations suggest that polyhexanide could be used safely for decolonization of carriers of chlorhexidine-resistant S. aureus strains; they also highlight the need for careful use of polyhexanide at low antiseptic concentrations.
Insights
Polyhexanide shows promise as an alternative decolonization agent for MRSA. While in vitro studies indicated potential for reduced susceptibility and cross-resistance to certain antibiotics, in vivo use did not show these issues, suggesting safe application.
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Infectious Diseases
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to resistance to existing decolonization agents like mupirocin and chlorhexidine.
- The need for alternative antiseptic molecules is critical to combat MRSA infections and colonization.
- Polyhexanide is a promising topical antiseptic with no reported severe adverse reactions or bacterial resistance.
Purpose of the Study:
- To evaluate the potential for developing strains with reduced polyhexanide susceptibility.
- To investigate cross-resistance between polyhexanide, chlorhexidine, and clinical antibiotics.
- To assess the safety and efficacy of polyhexanide for MRSA decolonization in vitro and in vivo.
Main Methods:
- Prolonged stepwise exposure of MRSA to low concentrations of polyhexanide in broth culture to induce reduced susceptibility in vitro.
- Genomic analysis to identify genetic changes associated with reduced polyhexanide susceptibility.
- In vivo studies during clinical polyhexanide decolonization treatment to monitor susceptibility and cross-resistance.
Main Results:
- In vitro studies demonstrated the emergence of reduced polyhexanide susceptibility after prolonged exposure.
- Reduced polyhexanide susceptibility was linked to genomic changes in mprF and purR genes, and decreased susceptibility to daptomycin and cell wall-active antibiotics.
- Importantly, in vitro reduced susceptibility to polyhexanide did not lead to cross-resistance with chlorhexidine. In vivo treatment showed no reduced polyhexanide susceptibility or chlorhexidine cross-resistance.
Conclusions:
- Polyhexanide can be safely used for decolonizing carriers of chlorhexidine-resistant Staphylococcus aureus strains.
- The study highlights the importance of judicious use of polyhexanide, particularly at low antiseptic concentrations, to prevent potential resistance development.
- Polyhexanide represents a viable alternative antiseptic for MRSA decolonization, with favorable in vivo outcomes regarding resistance and cross-resistance.
