High prevalence of cross-class azole resistance among Candida isolates from oropharyngeal candidiasis in HIV-positive cohort in southeast Nigeria

Abstract

Oral candidiasis remains a prevalent opportunistic infection in people living with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), particularly in low-resource settings. The increasing prevalence of non-albicans Candida species and widespread resistance to commonly used azole antifungals present a major therapeutic challenge. This study investigated the prevalence and azole antifungal susceptibility patterns of Candida (C) species isolated from people living with HIV in southeast Nigeria. A total of 514 oral swab samples were collected from HIV-positive patients selected using a systematic random sampling technique. The samples were cultured on Sabouraud dextrose agar and Candida species were identified using CHROMagar, germ tube, microscopy and sugar fermentation tests. Antifungal susceptibility was determined using the Kirby-Bauer disk diffusion method against several azole agents. Multivariate analysis was conducted to identify predictors of resistance to azole antifungals, with p < 0.05 set as the threshold for statistical significance. Candida species were isolated in 195 (37.9%) patients. The most prevalent species was C. albicans complex (19.3%), followed by C. glabrata (12.5%), C. krusei (5.1%), and C. tropicalis (1.2%), including mixed infections of two or more Candida species (0.4%). Near-universal resistance (99.5%) was observed for fluconazole, ketoconazole, itraconazole, and voriconazole. Notably, clotrimazole demonstrated a marked resurgence in sensitivity, with 74.4% of the isolates remaining susceptible, suggesting a possible shift in susceptibility trends. No socio-demographic or clinical characteristics were found to be statistically significant. Oral Candida infection was common in this HIV-positive cohort, involving both Candida albicans complex and non-albicans Candida species. Near-universal cross-species resistance to systemic azoles suggests that empirical azole therapy is increasingly unreliable and requires re-evaluation. In contrast, preserved susceptibility to clotrimazole supports its use for uncomplicated oropharyngeal candidiasis, where alternative agents and routine susceptibility testing are limited. These findings highlight the need to revise local treatment protocols, strengthen species-level diagnosis, targeted susceptibility testing, and antifungal stewardship. Not applicable.