Impact of fluconazole non-susceptibility on 30-d mortality in Candida tropicalis invasive candidiasis: Insights from a region with low resistance prevalence

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-d 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-d 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-d 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-d 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. CONCLUSIONS: The 30-d 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.