Abstract
Recurrent vulvovaginal candidiasis (RVVC) is one of the most prevalent fungal infections in humans, especially in developing countries; however, it is underestimated and regarded as an easy-to-treat condition. RVVC may be caused by dysbiosis of the microbiome and other host-, pathogen-, and antifungal drug-related factors. Although multiple studies on host-related factors affecting the outcome have been conducted, such studies on Candida-derived factors and their association with RVVC are lacking. Thus, fluconazole-tolerant (FLZT) isolates may cause fluconazole therapeutic failure (FTF), but this concept has not been assessed in the context of Candida-associated vaginitis. Iran is among the countries with the highest burden of RVVC; however, comprehensive studies detailing the clinical and microbiological features of this complication are scarce. Therefore, we conducted a 1-year prospective study with the aim to determine the RVVC burden among women referred to a gynecology hospital in Tehran, the association of the previous exposure to clotrimazole and fluconazole with the emergence of FLZT and fluconazole-resistant (FLZR) Candida isolates, and the relevance of these phenotypes to FTF. The results indicated that about 53% of the patients (43/81) experienced RVVC. Candida albicans and C. glabrata constituted approximately 90% of the yeast isolates (72 patients). Except for one FLZT C. tropicalis isolate, FLZR and FLZT phenotypes were detected exclusively in patients with RVVC; among them, 27.9% (12/43) harbored FLZR strains. C. albicans constituted 81.2% of FLZR (13/16) and 100% of the FLZT (13/13) isolates, respectively, and both phenotypes were likely responsible for FTF, which was also observed among patients with RVVC infected with fluconazole-susceptible isolates. Thus, FTF could be due to host-, drug-, and pathogen-related characteristics. Our study indicates that FLZT and FLZR isolates may arise following the exposure to over-the-counter (OTC) topical azole (clotrimazole) and that both phenotypes can cause FTF. Therefore, the widespread use of OTC azoles can influence fluconazole therapeutic success, highlighting the necessity of controlling the use of weak topical antifungals among Iranian women.
Highlights
Fungi are major components of the human microbiome (Rolling et al, 2020) and are associated with approximately 1.7 billion superficial fungal infections (SFIs) and 1.5 million deaths due to invasive fungal infections (IFIs) (Brown et al, 2012)
There was no significant difference in age and the underlying conditions between the VVC and recurrent vulvovaginal candidiasis (RVVC) groups
62% of patients with RVVC had persistent vaginal candidiasis (28/43), whereas for all patients with VVC the infection was cleared after the first use of azoles and no signs of infection were recorded through the entire follow-up period
Summary
Fungi are major components of the human microbiome (Rolling et al, 2020) and are associated with approximately 1.7 billion superficial fungal infections (SFIs) and 1.5 million deaths due to invasive fungal infections (IFIs) (Brown et al, 2012). Vulvovaginal candidiasis (VVC) is one of the most prevalent manifestations of SFIs, and it is estimated that 75% of women experience at least one VVC episode during their lifetime (Brown et al, 2012; Denning et al, 2018). Approximately 138 million women suffer from recurrent vulvovaginal candidiasis (RVVC) annually, and this number is projected to reach 158 million by 2030 (Denning et al, 2018). Fluconazole resistance phenotype is due to stable genomic changes with visible growth of higher than minimum inhibitory concentration (MIC) at 24 h endpoint in the presence of drug. Drug tolerance has been studied in the context of candidemia, its role in VVC remains unclear
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