Candidemia is a major healthcare-associated bloodstream infection with high mortality, requiring ongoing surveillance to guide management. This retrospective study analyzed 306 candidemia episodes diagnosed between 2015 and 2024 at a Spanish tertiary-care hospital, comparing two periods (2015–2019 vs. 2020–2024). The overall incidence was 0.79 episodes per 1,000 admissions, with peaks in 2021 and 2024. Candida albicans was the most common species (44.8%), followed by Candida parapsilosis (19.0%) and Nakaseomyces glabrata (15.7%). A significant epidemiological shift occurred in the later period, with increased C. albicans, decreased C. parapsilosis, and emergence of N. glabrata as the second most frequent species. ICU-related cases rose significantly during the COVID-19 period. Diagnostic turnaround times improved, including faster blood culture positivity and species identification by MALDI-TOF, supported by rapid PCR testing with high sensitivity (91.7%). Antifungal resistance to fluconazole was notable in N. glabrata (42.3%). Empirical echinocandin use increased, alongside greater targeted fluconazole therapy. Antimicrobial stewardship interventions, mainly de-escalation strategies, were widely implemented after 2019. Overall mortality was 40.8%, with a decline observed in 2023–2024. These findings suggest that integrated diagnostic and stewardship strategies may improve outcomes, though causal relationships require further study.

Candidemia is a major healthcare-associated bloodstream infection with high mortality, requiring ongoing surveillance to guide management. This retrospective study analyzed 306 candidemia episodes diagnosed between 2015 and 2024 at a Spanish tertiary-care hospital, comparing two periods (2015–2019 vs. 2020–2024). The overall incidence was 0.79 episodes per 1.000 admissions, with peaks in 2021 and 2024. Candida albicans was the most common species (44.8%), followed by Candida parapsilosis (19.0%) and Nakaseomyces glabrata (15.7%). A significant epidemiological shift occurred in the later period, with increased C. albicans, decreased C. parapsilosis, and emergence of N. glabrata as the second-most frequent species. ICU-related cases rose significantly during the COVID-19 period. Diagnostic turnaround times improved, including faster blood culture positivity and species identification by MALDI-TOF, supported by rapid PCR testing with high sensitivity (91.7%). Antifungal resistance to fluconazole was notable in N. glabrata (48.1%). Empirical echinocandin use increased, alongside greater targeted fluconazole therapy. Antimicrobial stewardship interventions, mainly de-escalation strategies, were widely implemented after 2019. Overall mortality was 40.8%, with a decline observed in 2023–2024. These findings suggest that integrated diagnostic and stewardship strategies may improve outcomes, though causal relationships require further study.