BACKGROUND: This study assesses the impact of fluconazole resistance on 30-day all-cause mortality and 1-year recurrence in patients with Candida parapsilosis bloodstream infections (BSI). METHODS: A multicenter retrospective study was performed at 3 hospitals in Italy and Spain between 2018 and 2022. Adult patients with positive blood cultures for C. parapsilosis who received appropriate targeted therapy with either echinocandins or fluconazole were included. RESULTS: Among 457 patients, 196 (42.9%) had fluconazole-resistant C. parapsilosis (FLZR-CP) BSI and 261 (57.1%) had fluconazole-susceptible C. parapsilosis (FLZS-CP) BSI. All FLZR-CP patients received targeted echinocandins, while FLZS-CP patients received either echinocandins (60.5%) or fluconazole (39.5%). Unadjusted 30-day all-cause mortality rates were 28.6% for FLZR-CP and 28.4% for FLZS-CP (log-rank test, P = .998). In multivariable analysis, increased mortality was associated with age (adjusted hazard ratio [aHR] 1.03 per year
95% confidence interval [CI], 1.01-1.05
P = .0005), solid tumor (aHR 1.91
95% CI, 1.06-3.46
P = .0302), previous antifungal treatment (aHR 1.84
95% CI, 1.12-3.10
P = .0192), and septic shock (aHR 2.39
95% CI, 1.42-4.06
P = .0010), but not fluconazole resistance (aHR 1.00
95% CI, .62-1.63
P = .9864) nor the type of initial antifungal therapy (aHR 1.46
95% CI, .69-3.06
P = .3202). Propensity score-matched analysis showed no 30-day all-cause mortality difference between echinocandin-treated FLZR-CP and fluconazole-treated FLZS-CP patients (HR 0.81
95% CI, .37-1.75
P = .5915). However, a higher 1-year recurrence risk was observed in FLZR-CP patients (odds ratio, 7.37
95% CI, 2.11-25.80
P = .0018). CONCLUSIONS: Our results suggest that fluconazole resistance is not associated with a higher mortality risk in patients with C. parapsilosis BSI, though 1-year recurrence rates were higher in the FLZR-CP group.