Evolution of Vaginal Candida spp. over Eight Years: Species Stability and Variability in Antifungal Susceptibility Classifications Using the Integral System YEASTS Plus

Vulvovaginal candidiasis is caused predominantly by Candida albicans, but non-albicans species differ in antifungal susceptibility, and surveillance based on commercial susceptibility systems must be read against their analytical limitations. We retrospectively analyzed 2789 vaginal Candida isolates from 2789 unique patients recovered at Pelican Hospital, Oradea, Romania, between August 2018 and July 2026, tested with the Integral System YEASTS Plus colorimetric system and grouped into four two-year periods. Classifications for clotrimazole, econazole, miconazole, fluconazole and nystatin were analyzed as recorded, without conversion into EUCAST categories. C. albicans accounted for 84.6% of isolates, Nakaseomyces glabratus (Candida glabrata) for 8.4%, Pichia kudriavzevii (Candida krusei) for 3.8% and the C. parapsilosis complex for 2.8%, and the distribution of species assignments did not change across periods (p = 0.532). Phenotypes were strongly species dependent: P. kudriavzevii, which is intrinsically resistant to fluconazole, was never classified as fluconazole-susceptible (0/107); only 37.2% of C. parapsilosis complex isolates were classified as nystatin-susceptible; and 97.3% of C. albicans isolates were classified as fluconazole-susceptible, without temporal change. Directional trends surviving multiplicity correction were confined to C. albicans but reflected a synchronous final-period rise across pharmacologically distinct agents, while clotrimazole classifications fell and recovered simultaneously in all three non-albicans species during 2020–2022, unlike econazole. These structures, and the progressive enrichment of later periods with newly included patients inherent to the first-isolate design, are more consistent with analytical variation and cohort structure than with resistance evolution. Commercial colorimetric classifications should not be equated with reference MIC-based categories, and the species–drug signals identified require confirmation by reference methods.