In vitro evaluation of the antimicrobial activity of chlorhexidine alone or in combination with ketoconazole or miconazole against clinical isolates of Malassezia pachydermatis and multidrug-resistant Staphylococcus pseudintermedius

Background. Staphylococcus pseudintermedius ( SP ) and Malassezia pachydermatis ( MP ) are common causes of canine skin infections associated with increasing antimicrobial resistance. Topical products containing chlorhexidine and azoles have been utilized to treat these infections. However, a limited number of studies have assessed the interactions between chlorhexidine and azoles against SP and MP . Hypothesis/Objectives. To assess efficacy and potential additivity/synergy between chlorhexidine and azoles against clinical isolates of MP and multidrug-resistant SP ( MDR-SP ). Materials and Methods. A total of 30 MDR-SP and 30 MP isolates were tested using a modified broth microdilution method. Six twofold dilutions of 2% chlorhexidine gluconate, 1% miconazole nitrate and 0.15% ketoconazole were tested alone and in combination. Minimum inhibitory (MIC) and bactericidal/fungicidal (MBC/MFC) concentrations were recorded, and synergy, additivity or antagonism was calculated. Result. For MDR-SP , the combinations of chlorhexidine/miconazole ( P =0.003) and chlorhexidine/ketoconazole ( P <0.0001) resulted in lower MICs than chlorhexidine alone. Only the chlorhexidine/ketoconazole combination had lower MBCs ( P =0.0071) than chlorhexidine alone. For MP , only the chlorhexidine/ketoconazole combination had lower MICs ( P <0.0001) than chlorhexidine alone. Both combinations of chlorhexidine/miconazole ( P =0.0028) and chlorhexidine/ketoconazole ( P <0.0001) resulted in lower MFCs than chlorhexidine alone. Chlorhexidine/miconazole combination showed synergy in three MDR-SP isolates, but in none of the MP isolates. Chlorhexidine/ketoconazole showed synergy for 1 out of 30 MDR-SP and 19 out of 30 MP isolates. Conclusions and Clinical Relevance. These results suggest that chlorhexidine/azole combinations are an effective topical treatment for MDR-SP and MP infections. Further studies should assess the efficacy of commercial products containing these compounds and their efficacy in vivo .