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Multicenter Study
. 2025 Mar 17;80(3):540-550.
doi: 10.1093/cid/ciae603.

Impact of Fluconazole Resistance on the Outcomes of Patients With Candida parapsilosis Bloodstream Infections: A Retrospective Multicenter Study

Antonio Vena  1   2 , Giusy Tiseo  3 , Marco Falcone  3 , Claudia Bartalucci  1   2 , Cristina Marelli  2 , Mario Cesaretti  3 , Vincenzo Di Pilato  4   5 , Pilar Escribano  6   7   8   9 , Arianna Forniti  3 , Daniele Roberto Giacobbe  1   2 , Jesus Guinea  6   7   8   9 , Alessandro Limongelli  1   2 , Antonella Lupetti  10 , Marina Machado  6   7   8 , Malgorzata Mikulska  1   2 , Jon Salmanton-García  11   12   13 , Ana Soriano-Martin  6   7   8 , Lucia Taramasso  1   2 , Maricela Valerio  6   7   8   14 , Emilio Bouza  6   7   8   14 , Patricia Muñoz  6   7   8   14 , Matteo Bassetti  1   2
Affiliations
Multicenter Study

Impact of Fluconazole Resistance on the Outcomes of Patients With Candida parapsilosis Bloodstream Infections: A Retrospective Multicenter Study

Antonio Vena et al. Clin Infect Dis. .

Abstract

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.

Keywords: Candida bloodstream infection; Candida parapsilosis; echinocandins; fluconazole resistance; mortality.

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Conflict of interest statement

Potential conflicts of interest . Outside the submitted work, A. V. reports personal fees for speaker/advisor from Pfizer Inc, Shionogi, Tillotts Pharma, Menarini, Gilead Italia, Mundipharma, Advanz pharma and MSD. Outside the submitted work, D. R. G. reports investigator-initiated grants from Pfizer Inc, Shionogi, BioMérieux, Tillotts Pharma, Menarini, and Gilead Italia, personal fees for speaker/advisor from Pfizer Inc, Menarini, BioMérieux, and Tillotts Pharma. Outside the submitted work, M. B. reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Bayer, BioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, and Shionogi. Outside the submitted work, J. S. G. has received speaker honoraria by Gilead, Menarini, and Pfizer; travel grant by AstraZeneca and was on the advisory board for Pfizer. Outside the submitted work, P. M. reports investigator-initiated grants from Pfizer Inc, Shionogi, Tillotts Pharma, Menarini, and Gilead. Outside the submitted work, V. D. P. reports payments for participation in a company sponsored speaker's bureau from A.d.a, consulting fee from Biorad, supports for attending meetings from Arrow Diagnostics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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