Abstract
BACKGROUND: The emergence of fluconazole-resistant non-albicans Candida (NAC) species poses a major challenge for the long-term management of candidiasis, particularly in immunocompromised patients. METHODS: A systematic search of four major databases was performed in accordance with the PRISMA 2020 guidelines to identify studies reporting fluconazole resistance among NAC species. Data were pooled using a random-effects model to estimate resistance prevalence with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s Q test and the I² statistic. RESULTS: This global meta-analysis evaluated the prevalence of fluconazole resistance among NAC species. Resistance rates varied substantially across species, with C. krusei showing the highest pooled resistance (78.3%), followed by C. glabrata (15.9%), C. tropicalis (13.0%), and C. dubliniensis (11.1%). Subgroup analyses revealed increasing temporal trends in resistance, particularly for C. krusei, C. parapsilosis, and C. tropicalis, with statistically significant increases confirmed by meta-regression (p < 0.05). Geographic disparities were evident: C. glabrata resistance was highest in South Korea (80.5%) and lowest in Peru (1.3%), while C. krusei resistance peaked in the Americas (96.7%) and was lowest in Africa (34.1%). Resistance estimates also differed by antifungal susceptibility testing (AST) method, particularly for C. krusei, where MIC-based methods identified substantially higher resistance than other approaches. Evidence of publication bias was detected for C. glabrata, C. krusei, and C. dubliniensis, suggesting possible overestimation of resistance rates. CONCLUSION: Fluconazole resistance among NAC species is rising globally, with particularly notable increases in C. krusei, C. glabrata, C. tropicalis, and C. dubliniensis. Significant geographic and methodological variations underscore the need for region-specific antifungal stewardship and standardized susceptibility testing. Addressing publication bias, strengthening surveillance systems, and developing alternative antifungal therapies are critical for the effective management of invasive candidiasis. CLINICAL TRIAL NUMBER: Not applicable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-026-12653-8.