Risk factors for isolation of fluconazole and echinocandin non-susceptible Candida species in critically ill patients

J Med Microbiol. 2021 Aug;70(8). doi: 10.1099/jmm.0.001401.


Introduction. Resistance rates to azoles and echinocandins of Candida spp. increased over the last decade.Hypothesis/Gap Statement. Widespread use of antifungals could lead to development and dissemination of resistant Candida spp.Aim. To identify risk factors for isolation of Candida spp. non-susceptible to either fluconazole or echinocandins.Methodology. All patients hospitalized in the Intensive Care Unit (ICU) of the University General Hospital of Patras, Greece with Candida spp. isolated from clinical specimens during a ten-year period (2010-19) were included. Candida isolates were identified using Vitek-2 YST card. Consumption of antifungals was calculated.Results. During the study period, 253 isolates were included. C. non-albicans predominated (64.4 %) with C. parapsilosis being the most commonly isolated (42.3 %) followed by C. glabrata (nomenclatural change to Nakaseomyces glabrataa; 8.7 %) and C. tropicalis (11.9 %). Among all isolates, 45.8 and 28.5 % were non-susceptible and resistant to fluconazole, respectively. Concerning echinocandins, 8.7 % of isolates were non-susceptible to at least one echinocandin (anidulafungin or micafungin) and 3.1 % resistant. Multivariate analysis revealed that hospitalization during 2015-19, as compared to 2010-14, isolate being non-albicans or non-susceptible to at least one echinocandin was associated with isolation of fluconazole non-susceptible isolate. Administration of echinocandin, isolate being C. glabrata or C. tropicalis, or Candida spp. non-susceptible to fluconazole were independently associated with isolation of Candida spp. non-susceptible to at least one echinocandin. Fluconazole's administration decreased during the study period, whereas liposomal-amphotericin B's and echinoncandins' administration remained stable.Conclusion. Fluconazole's non-susceptibility increased during the study period, despite the decrease of its administration. Although echinocandins' administration remained stable, non-susceptibility among Candida spp. increased.

Keywords: Candida albicans; candidaemia; echinocandins; fluconazole; fluconazole resistance; liposomal-amphotericin B.

MeSH terms

  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Candida / classification
  • Candida / drug effects*
  • Candida / isolation & purification
  • Candidiasis / diagnosis
  • Candidiasis / drug therapy
  • Candidiasis / epidemiology
  • Candidiasis / microbiology*
  • Critical Illness*
  • Drug Resistance, Fungal*
  • Fluconazole / pharmacology*
  • Fluconazole / therapeutic use
  • Greece / epidemiology
  • Humans
  • Intensive Care Units
  • Microbial Sensitivity Tests
  • Mycological Typing Techniques
  • Risk Factors


  • Antifungal Agents
  • Fluconazole