Global Epidemiology and Antifungal Resistance Trends of Candida Species (2000-2025): A Systematic Review of Species Distribution, Outbreaks, and Emerging Multidrug Resistance

Background: The objective is to synthesize data on the distribution, antifungal resistance trends of Candida spp., hospital outbreaks and emergence of multidrug resistance across the world from 2000 to 2025. Material and Methods: A systematic review was carried out following PRISMA 2020 guidelines. Systematic reviews, meta-analyses, multi-country surveillance reports, cohort studies, cross-sectional studies and outbreak investigations were identified via PubMed/MEDLINE, Embase, Web of Science and Scopus databases for Candida species-level identification from human clinical infections. Clinical specimen source, geographic distribution, antifungal susceptibility, mechanisms of antifungal resistance, outbreak characteristics and outcomes of death were retrieved. Due to the differences in the study platforms, breakpoints, clinical settings and surveillance techniques across regions, findings were summarized narratively and supplemented with pooled estimates from eligible published meta-analyses. Results: After duplicates were removed, 139 studies contributed to the qualitative synthesis from 2864 records of which 755 full-text articles were evaluated. Candida albicans remained important, but non-albicans Candida species collectively exceeded Candida albicans in several regions and clinical settings. Candida tropicalis, Candida parapsilosis, Candida glabrata, and Candida auris showed the most clinically relevant shifts. Fluconazole resistance was particularly high in Candida auris and increased in Candida tropicalis in parts of Asia. Echinocandin resistance was increasingly reported in Candida glabrata and Candida parapsilosis. Candida auris caused multiple healthcare-associated outbreaks because of environmental persistence, delayed identification, multidrug resistance, and inter-facility transmission. Conclusion: Candida epidemiology has changed substantially over the last 25 years. Species-level identification, standardized susceptibility testing, active surveillance, infection prevention, and antifungal stewardship are essential to reduce morbidity, mortality, and outbreak risk from resistant Candida infections.

Keywords: Candida; candidemia; antifungal resistance; Candida auris; systematic review.