Elevated in vitro activity of ibrexafungerp against azole-resistant Candida isolates from Vulvovaginal Candidiasis (VVC): a multicentric study from India

Vulvovaginal candidiasis (VVC) is complicated by an increase in non-albicans Candida (NAC) species, biofilm formation and rising fluconazole resistance, limiting the effectiveness of conventional therapies. Ibrexafungerp, a newer antifungal, offers a novel therapeutic option owing to its distinct mechanism of action against azole-resistant isolates. A total of 400 isolates from four centres (PGIMER, Chandigarh; RIMS, Imphal; BHU, Varanasi and MGMMC, Indore) were included in this study. Species identification was performed by MALDI-TOF MS, and antifungal susceptibility testing (AFST) as per Clinical and Laboratory Standards Institute (CLSI) M27 guidelines. Candida albicans was the most prevalent species across the four centres (72%, 74%, 34% and 47% from Chandigarh, Imphal, Varanasi and Indore respectively). Among NAC species, Nakaseomyces glabratus was predominant in Chandigarh (19%) and Imphal (14%), and Candida tropicalis in Varanasi (31%) and Indore (33%). AFST showed higher resistance in C. albicans to fluconazole - 11% in Chandigarh, 3% in Varanasi, and 2% in Imphal and Indore. C. tropicalis exhibited resistance to fluconazole and voriconazole amongst isolates from Varanasi only. Mutations in ERG11 gene attributing to azole-resistance included A114V, F145L amongst the fluconazole-resistant isolates. Biofilm formation of C. albicans was statistically significant in PGIMER compared to other centres. Ibrexafungerp MICs among C. albicans isolates ranged from 0.06 to 2 µg/ml, among C. tropicalis isolates from 0.12 to 1 µg/ml, among N. glabratus isolates from 0.25 to 1 µg/ml. With this, we derive that Candida albicans remains the predominant causative agent of VVC, however, NACs are increasing. Fluconazole is still the drug of choice to treat VVC, but with increasing resistance, the use of ibrexafungerp could be a promising alternative strategy.