Study on Vulvovaginal Candidiasis: Clinical Epidemiology and <i>in vitro</i> Susceptibility of Pathogenic Yeasts in China

Abstract

Background: Vulvovaginal candidiasis (VVC) is a common vaginal infection. We aim to investigate the clinical epidemiology of VVC and the in vitro antifungal susceptibility of Candida spp. collected from different regions of China, so as to provide a guideline for the appropriate use of antifungals in clinical settings. Methods: Candida isolates from VVC patients and questionnaires were collected from 12 hospitals across the China from September 2017 to March 2018. Species were identified by germ tube test, clamydospore formation, CHROMagar medium and DNA sequencing. Susceptibility to fluconazole (FLC), itraconazole (ITC), voriconazole (VOC), posaconazole (POS), miconazole (MIC), econazole (ECO), clotrimazole (CLZ), nystatin (NYS), amphotericin B (AMB), caspofungin (CAS), and terbinafine (TBF) was determined using the CLSI broth microdilution method (M27-E4). The in vitro data were also evaluated with updated clinical breakpoints and epidemiological cut-off values. Findings: A total of 602 cases were enrolled in this study, of which 253 (42%) were uncomplicated VVC and 349 (58%) were complicated. Among complicated VVC, 26% were RVVC. The subjects were between 16 and 64 years of age, of which 60% were between 25 and 35 years of age. A total of 543 strains were isolated from these VVC patients. The most commonly identified species was C.albicans (84.71%), followed by C.glabrata (8.66%), Meyerozyma caribbica (1.29%), Pichia guilliermondii (1.29%), C.tropicalis (0.92%), Pichia kudriavzevii (0.92%), C.parapsilosis (0.55%), Candida nivariensis (0.55%), Issatchenkia orientailis (0.55%) and less common yeasts(0.55%). The overall susceptibility rates of C.albicans to FLC, VOC and CAS were all greater than 80%, and the resistance rates were less than 10%. Most of C.albicans isolates were WT to ITC (86%), POS (95%) and AMB (98%). Most of C.glabrata (98%) were dose-dependently susceptible to FLC. All of C.glabrata isolates were WT to both ITC and AMB, while most were WT to both VOC (85%) and POS (91.5%).The proportion of NWT strains to FLC in RVVC was much higher than that in other types of VVC(33% vs . 23%, P <0.05). The proportions of WT strains to ITC in complicated VVC and RVVC were all over 80%, which were much higher than that to FLC( P <0.01). CLZ showed the lowest MIC 90 (0.06ug/ml)against C.albicans, and the MICs of CLZ among non-albicans Candida (NAC) were all <2ug/ml. Interpretation: VVC was more frequent in women of childbearing age. C.albicans (84.71%) was still the predominant species of VVC in China, while C.glabrata (56.6%) was the main species in NAC. Most C.albicans strains isolated from uncomplicated VVC in different regions of China were still susceptible to the commonly used azoles, including FLC and ITC, which could be used as empirical treatment. However, FLC may not be the first choice for the treatment of complicated VVC, especially RVVC. In both cases, ITC was more appropriate treatment. CLZ could be recommended as a good choice of topical drugs for VVC. As for new drugs, POS is promising for the refractory cases. Funding Statement: This study was supported by National Science and Technology Major Project (2018ZX10734404), the CAMS Initiative for Innovative Medicine (2016-I2M-3-021), National Natural Science Foundation of China (Grant No. 81573059), the Basical Scientific Research Fund Projects of Chinese Academy of Medical Sciences (No. 2018PT31013) and Nanjing Clinical Medicine Research Center Project (No.2019060001). Declaration of Interests: All authors declare that they have no conflicts of interest. Ethics Approval Statement: The study has been approved by the ethics committee of the hospital, and all patients have signed informed consent (version number and date:1.0, 2017.02.16).