OBJECTIVE: Fluconazole non-susceptibility (FNS) in Candida tropicalis is an escalating global concern. We aimed to evaluate the clinical and molecular factors associated with 30-day mortality among patients with C. tropicalis invasive candidiasis (IC). METHODS: We performed a retrospective cohort study involving C. tropicalis IC episodes at a medical center in southern Taiwan (2018-2023). Multivariable logistic regression identified independent correlates of 30-day mortality. Furthermore, a subset of FNS isolates underwent MIC profiling, ERG11/UPC2 sequencing, qRT-PCR of target and efflux-pump genes, and phylogenetic analysis to investigate molecular mechanisms. RESULTS: We identified 341 C. tropicalis IC patients, with 30-day mortality rate of 45.8%. The average FNS rate was 8.2%, and the annual proportion among sterile-site isolates (ranging from 3.8% to 12.5%) exhibited no significant temporal trend. Independent factors associated with higher mortality included older age (AOR 1.01 per year), fungemia (AOR 2.50), recent chemotherapy (AOR 1.62), and recent exposure to carbapenems (AOR 1.40), daptomycin (AOR 2.60), and polymyxins (AOR 2.49). Dialysis was associated with lower mortality (AOR 0.48). Importantly, neither FNS nor empiric echinocandin therapy was independently associated with 30-day mortality. Molecularly, FNS isolates were characterized by ERG11 Y132F±S154F, a recurrent UPC2 Q289L substitution, up-regulation of efflux pump genes (CDR1, CDR2, and MDR1), and predominance of DST538/DST544 lineages. CONCLUSION: The 30-day mortality in C. tropicalis IC was primarily driven by host factors and infection site rather than FNS status. In healthcare settings with a low FNS prevalence, these findings suggest that empiric fluconazole therapy remains a reasonable treatment option.
Lin et al. (Mon,) studied this question.