Fluconazole Susceptibility and ERG11 Gene Expression in Candida Species Associated With Vulvovaginal Candidiasis

Abstract

Summary V V ulvovaginal candidiasis is both treatable and mild, but when left untreated, is a possible risk for many complications. A number of antifungal agents especially azoles are available to treat vulvovaginal candidiasis. Fluconazole is recommended in various guidelines as the first drug of choice because it is less toxic and can be taken as a single oral dose. Several mechanisms of resistance to azoles have been described in Candida. These include increased expression of the drug efflux pump genes such as MDR1, CDR1 and CDR2 and also over expression and mutations of ERG11 gene which encodes for lanosterol 14α-demethylase which results in production of a large amount of lanosterol 14α-demethylase and this favours continuous synthesis of ergosterol and maintenance of the integrity of the cell wall which enables Candida to resist fluconazole. The present study aimed at determining the in vitro antifungal susceptibility profile of isolated Candida species especially to fluconazole in cases of vulvovaginal candidiasis, also investigating fluconazole resistant and susceptible dose dependent (SDD) isolates for the expression of mutations of ERG11 gene and guide empirical antifungal treatment for the suspected cases of Candida vulvovaginitis. Hundred Candida isolates obtained from female patients attending the Obstetric and Gynecological outpatient clinic in Ain Shams University Hospitals were subjected to culture on SDA, Hichrome agar and germ tube test for species identification. Then antifungal susceptibility testing by disc diffusion method using disks of fluconazole, ketoconazole, itraconazole and nystatin was performed. ERG11 gene DNA mutations were detected in fluconazole resistant and susceptible dose dependent Candida isolates by real time PCR except Candida krusei which has inherent resistant to fluconazole. In the present study, Candida albicans was the predominant species and was isolated from (62%) of vaginal swabs while NCAC group was isolated from (38%) with the predominant species Candida glabrata (22%) followed by Candida krusei (10%), Candida tropicalis (4%) and no other specified (NOS) NCAC (2%).