Epidemiology, Significance and Clinical Outcomes of Bloodstream Infections Caused by Non-Candida and Non-Cryptococcus Yeasts.

Introduction: Fungaemia due to non-Candida and non-Cryptococcus yeasts is uncommon but clinically significant, particularly in immunocompromised hosts. We aimed to describe the epidemiology, microbiology and outcomes of bloodstream infections (BSIs) caused by these organisms.

Methods: We identified all BSIs due to non-Candida and non-Cryptococcus yeasts over a 20-year period using statewide laboratory and administrative health databases.

Results: Seventy-five unique episodes were identified. The most frequent genera were Trichosporon (n = 31, 41.3%), Rhodotorula (n = 26 34.7%) and Saccharomyces (n = 10, 13.3%) species. Antifungal susceptibility testing performed in 33 (44%) episodes revealed high MICs (> 16 mg/L) to echinocandins for Trichosporon and Rhodotorula species. Fluconazole MICs were universally elevated ( $\ge$  32 mg/L) in Rhodotorula spp. but lower in Saccharomyces cerevisiae (2-4 mg/L). Voriconazole and posaconazole had good in vitro activity across all genera where tested. Thirty-day mortality was 22.7%, with the highest rate observed in S. cerevisiae (50.0%). Mortality was associated with malignancy (aHR 4.71, 95% CI 1.00-22.25), heart failure (aHR 11.31, 95% CI 1.66-77.14) and intensive care unit (ICU) admission (aHR 7.05, 95% CI 0.99-50.36). The presence of a central line may be protective (aHR 0.17, 95% CI 0.03-1.04). Rhodotorula infection was associated with lower mortality on univariable analysis (HR 0.11, 95% CI 0.14-0.86) compared with Trichosporon species.

Conclusion: Although rare, fungaemia due to non-Candida and non-Cryptococcus yeasts is associated with significant mortality and antifungal resistance. Species identification and susceptibility testing are crucial to guide treatment. Increased awareness is essential in high-risk patients, particularly those with malignancy, heart failure, or requiring ICU admission.