Clinical Characteristics, Antifungal Exposure, and 90-Day Mortality of PCR-Identified Candidemia According to Presumed Species-Level Fluconazole Susceptibility

Rapid species identification frequently informs early antifungal decision-making before isolate-level antifungal susceptibility testing becomes available. Clinicians therefore commonly rely on presumed species-level fluconazole susceptibility to guide initial therapy. Whether these presumed susceptibility categories identify clinically distinct patient populations with different treatment patterns and outcomes remains uncertain. We conducted a retrospective cohort study using TriNetX Research Network (May 2017-November 2023) including adults with PCR-identified candidemia. Patients were categorized as presumed fluconazole susceptible (FS) (Candida albicans, C. parapsilosis, C. tropicalis) or presumed fluconazole nonsusceptible (FNS) (Nakaseomyces glabratus, Pichia kudriavzevii, Candida auris). Clinical characteristics, antifungal treatment patterns, and 90-day all-cause mortality were evaluated using inverse probability of treatment weighting (IPTW) and Cox proportional hazards models. Among 1,171 patients, 43% were categorized in the FNS group. Compared with the FS group, patients in the FNS group were older, had greater comorbidity burden, and more frequently received echinocandins, whereas azole exposure was more common in the FS group. Despite similar crude 90-day mortality (23.9% vs 23.3%), IPTW-adjusted analysis demonstrated lower survival among patients in the FS group (adjusted HR 1.41, 95% CI 1.09-1.82, p = 0.009). Within-group analyses identified variables independently associated with mortality, with PCR-identified N. glabratus independently associated with mortality only within the FNS group. Species categorized as presumed FNS accounted for nearly half of PCR-identified candidemia cases and were associated with clinically distinct patient populations characterized by different baseline characteristics and mortality associations. Rapid species identification conveys clinically relevant information beyond anticipated fluconazole susceptibility while awaiting isolate-level AFST.