Synergistic anticandidal activity of menthol in combination with itraconazole and nystatin against clinical Candida glabrata and Candida krusei isolates

Background: Candida glabrata (C glabrata) and C. krusei are now emerging as serious hospital acquired infections in immunocompromised patients. Menthol, a terpenic compound, has been reported to have antifungal activity. Objectives: The aim of this study was to investigate the effect of menthol in combination with itraconazole or nystatin against C. glabrata and C. krusei isolates. Methods: The effects of menthol along with itraconazole and nystatin, were evaluated by the Clinical Laboratory Standards Institute (CLSI) M44-A and CLSI M27-A3 methods. The fractional inhibitory concentration index (FICI) was determined for menthol plus itraconazole and nystatin combinations using the checkerboard method. Results: The mean of minimum inhibitory concentration (MIC) values of menthol, nystatin and itraconazole were 53.2, 2.30 and 1.50 mu g/ml for C. glabrata isolates and 121, 1.08 and 038 mu g/ml for C krusei isolates, respectively. Menthol in combination with itraconazole or nystatin exhibited the synergistic effects against all species of Candida tested. FICI values for menthol plus itraconazole and nystatin combinations ranged from 0.250 to 0.561 and 0.139 to 0.623 for C. glabrata isolates, and 0.182 to 0.750 and 0.188 to 0.760 for C krusei, respectively. Conclusions: These results support the potential use of menthol as an anticandidal agent, and it can be used complementarily with other conventional antifungal agents. (C) 2017 Published by Elsevier Ltd.