Stability and and efficacy of combined nystatin and chlorhexidine against suspensions and biofilms of Candida albicans

Objective: Nystatin and chlorhexidine are extensively used in oral medicine; however, there is some controversy about the possibility of these drugs showing antagonism. To clarify this issue, this study investigated the efficacy and stability of nystatin and chlorhexidine in combination. Design: An in vitro study was conducted to analyze the effect of nystatin and chlorhexidine combined on Candida albicans ATCC 18804, using the drugs mixed as a single formulation and as independent formulations used sequentially with different time intervals between them. The minimum inhibitory concentration (MIC) and effects on C. albicans suspensions and biofilms were evaluated. Also, the stability of nystatin and chlorhexidine in a mixture was tested by high performance liquid chromatography (HPLC). Results: When nystatin and chlorhexidine were mixed in a single formulation, there was no significant difference in MIC compared to that of the drugs used alone (as the only treatment). However, when these drugs were used as independent formulations, sequentially with time intervals in between, their MICs were higher than the respective MIC of the drug used alone, except for the MIC of chlorhexidine with a 10-min interval. Nystatin/chlorhexidine combinations showed lower activity against C. albicans biofilms, except for that with a 30-min interval. The drugs when combined showed high percentages of degradation at all the times evaluated. Conclusions: The combination of nystatin and chlorhexidine seems to interfere with the efficacy of the drugs and to increase their rate of degradation.