Evaluation of synergistic action between nimesulide and the antifungals ketoconazole and nystatin on clinical cervical-vaginal isolates of Candida spp.

Abstract

Introduction: Antifungal resistance in cases of vulvovaginal candidiasis (VVC) increasingly affects women worldwide, being a recurrence in gynecological appointments. The need for effective new therapies and the difficulty of introducing antifungals into the pharmaceutical market makes drug combination a quick and interesting therapeutic strategy for solving such a problem. Objective: The present study aims to evaluate the association of nimesulide, a non-steroidal anti-inflammatory drug, with antifungals used in topical treatments for vaginal candidiasis (ketoconazole and nystatin). Secondarily, we link the susceptibility profile of clinical isolates from primary health care units in southern Brazil. Materials and methods: The broth micro dilution methodology was used for susceptibility testing, and the Checkerboard method was used to evaluate the synergistic effect of nimesulide with antifungals. Results and discussions: High percentages of isolates resistant to the tested antifungals were observed: 75% of the isolates were resistant to fluconazole and 36.1% to Iitraconazole, as well as 22.2% had low susceptibility to ketoconazole and 55% to nystatin. The combination of nimesulide and ketoconazole showed synergistic effect for 62.5% of Candida spp. tested, including C. albicans, C. glabrata and C. tropicalis isolates. On the other hand, the combination of nimesulide and nystatin resulted in 100% indifference.