Comparative effectiveness of echinocandins and liposomal amphotericin B for fluconazole-resistant Candida parapsilosis bloodstream infections

Antimicrob Agents Chemother. 2025 Nov 5;69(11):e0035525. doi: 10.1128/aac.00355-25. Epub 2025 Sep 30.

Abstract

Current therapeutic options for fluconazole-resistant Candida parapsilosis (FLZR-CP) bloodstream infections (BSI) are limited to echinocandins and liposomal amphotericin B (L-AmB). To the best of our knowledge, no real-world comparative effectiveness studies have assessed these agents. This study aimed to compare the effectiveness of echinocandins and L-AmB for the treatment of FLZR-CP BSI. This retrospective, observational study was conducted in two hospitals in Italy between January 2018 and December 2022. Eligible patients were adults (≥18 years old) with microbiologically confirmed FLZR-CP BSI who received targeted therapy with either echinocandins or L-AmB. Patients were matched (2:1) based on age, Charlson comorbidity index, presence of sepsis or septic shock, time to appropriate antifungal therapy (≤48 hours or > 48 hours from diagnosis), and infection source. A total of 63 patients were included (42 in the echinocandin group and 21 in the L-AmB group). In Cox regression, targeted therapy with echinocandins was not associated with increased mortality (adjusted hazard ratio 1.40; 95% confidence interval [CI] 0.33-5.92, P = 0.645). An exploratory sensitivity analysis including patients who did not receive source control yielded consistent results (P = 0.491). Furthermore, in the multivariable regression analysis, echinocandin therapy was not associated with an increased risk of persistent fungemia (adjusted odds ratio 1.61: 95% CI 0.43-5.99, P = 0.476). Treatment with echinocandins and L-AmB resulted in similar 30-day mortality and persistent fungemia rates in patients with FLZR-CP BSI. These findings confirm that echinocandins are a viable treatment option for C. parapsilosis BSI, even for patients with fluconazole-resistant strains.

Keywords: Candida bloodstream infection; Candida parapsilosis; echinocandins; fluconazole resistance; liposomal amphotericin B.

Publication types

  • Observational Study
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Amphotericin B* / pharmacology
  • Amphotericin B* / therapeutic use
  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Candida parapsilosis* / drug effects
  • Candida parapsilosis* / pathogenicity
  • Candidemia* / drug therapy
  • Candidemia* / microbiology
  • Candidiasis* / drug therapy
  • Candidiasis* / microbiology
  • Drug Resistance, Fungal / drug effects
  • Echinocandins* / pharmacology
  • Echinocandins* / therapeutic use
  • Female
  • Fluconazole* / pharmacology
  • Fluconazole* / therapeutic use
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Retrospective Studies

Substances

  • Antifungal Agents
  • Amphotericin B
  • liposomal amphotericin B
  • Fluconazole
  • Echinocandins