Antifungal susceptibility testing and determination of local epidemiological cut-off values for <i>Candida</i> species isolated from women with vulvovaginal candidiasis

The lack of clinical breakpoints and epidemiological cut-off values (ECOFFs) for antifungals prescribed for vulvovaginal candidiasis (VVC) make interpretation of antifungal susceptibility data difficult. This leads to empirical prescribing, poor clinical management and emergence of resistance. The <i>in vitro</i> susceptibilities of 152 <i>Candida albicans</i>, 105 <i>Candida parapsilosis</i>, 31 <i>Nakaseomyces glabratus,</i> and 8 <i>Pichia kudriavzevii</i> VVC isolates against eight antifungals, were determined according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) E.Def 7.4. The minimum inhibitory concentration (MIC) distributions were analyzed and local ECOFFs were determined visually and statistically. The <i>in vitro</i> activity of azoles was correlated with fluconazole susceptibility and clinical data were evaluated. The MICs of various azoles showed a significant correlation with the MICs of fluconazole and fluconazole non-wild type (WT) isolates had significantly higher MICs for other azoles. The estimated local ECOFFs for <i>C. albicans</i> were 0.016 mg/L (ketoconazole, clotrimazole), 0.06 mg/L (miconazole, econazole, itraconazole), 1 mg/L (fenticonazole), and 3,200 mg/L (boric acid). For <i>C. parapsilosis</i>, local ECOFFs were 0.06 mg/L (ketoconazole, clotrimazole, itraconazole), 1 mg/L (miconazole, econazole), 2 mg/L (fenticonazole), and 3,200 mg/L (boric acid). For <i>N. glabratus</i>, they were 1 mg/L (ketoconazole, clotrimazole, miconazole, itraconazole), 2 mg/L (econazole, fenticonazole), and 12,800 mg/L (boric acid). Non-WT isolates were detected for azoles in <i>N. glabratus</i> (10%-35%), <i>C. albicans</i> (5%-16%), and <i>C. parapsilosis</i> (≤ 3%). All isolates were WT for boric acid. Local ECOFFs were established for three major <i>Candida</i> species causing VVC, guiding the identification of non-WT isolates potentially associated with treatment failure.IMPORTANCEThe interpretation of <i>in vitro</i> susceptibility data of <i>Candida</i> isolates from women with vulvovaginal candidiasis (VVC) is challenging due to the lack of clinical breakpoints (CBPs) and epidemiological cut-off values (ECOFFs) for drugs used in VVC. In the present study, local ECOFFs were established for three major <i>Candida</i> species causing VVC, guiding the identification of non-wild type isolates potentially associated with treatment failure. This paper provides the framework for developing ECOFFs and ultimately CBPs that would help guide antifungal therapy of VVC.