Candida guilliermondii complex is characterized by high antifungal resistance but low attributable mortality: a report of 20 cases of candidaemia

Laura Judith Marcos-Zambrano, Felipe Pérez-García, Pilar Escribano Martos, Oscar Zaragoza, Emilio Bouza Santiago, Belén Padilla, Manuel Cuenca-Estrella, Jesus Guinea

Abstract: 

Background: Candida guilliermondii complex causes up to 2% of all cases of candidemia and is characterized by decreased susceptibility to azoles and echinocandins. Clinical data from patients with C. guilliermondii candidemia are scarce. We report clinical data for 20 patients with candidemia caused by C. guilliermondii. We also report the antifungal susceptibility of the isolates, their biofilm production, and their virulence as studied using Galleria mellonella larvae.

Material/methods: We described the risk factors and outcome of 20 patients with candidemia caused by C. guilliermondii complex admitted to Gregorio Marañon Hospital (n=7) or included in the CANDIPOP project, a multicenter population-based study on candidemia conducted in Spain (n=13). The incident isolates were identified using molecular methods, and the susceptibility of fluconazole, echinocandins, and amphotericin B was studied using the EUCAST Edef 7.2 procedure. Isolates with a fluconazole MIC ≥8 μg/mL were considered resistant. Biofilm formation was measured using the crystal violet (biomass production) and the XTT reduction (metabolic activity) assays. Virulence was studied using the G. mellonella model, and 6 C. albicans isolates were used as controls.

Results: Mean age was 50 (0-83) years, and half of the patients were male. The main predisposing conditions were central venous catheter (85%), malignancy (65%), immunosuppressants (50%), and neutropenia (35%). A high proportion had previously received antifungal agents (40%), mostly azoles (35%). Only 1 patient was in the ICU at the moment of the diagnosis. The catheter was removed in half of the patients. They received antifungal treatment with fluconazole (55%), echinocandins (45%), or amphotericin B (35%). Seven-day mortality and 30-day mortality were low (5% and 15%, respectively). The isolates were identified as C. guilliermondii sensu stricto (n= 16) and Candida fermentati (n=4). The geometric mean MIC of the antifungal agents was as follows: fluconazole, 5.27 μg/mL; caspofungin, 0.34 μg/mL; anidulafungin, 1 μg/mL; micafungin, 0.27 μg/mL; and amphotericin B, 0.31 μg/mL. Up to 25% (5/20) of the isolates were fluconazole-resistant. The isolates were moderate (55%) or low-biofilm-forming (45%) and mostly produced biofilms with low metabolic activity (65%). The G. mellonella model showed that C. guilliermondii was less virulent than C. albicans (6 vs 1 mean survival days, respectively; P<0.001).

Conclusions: Patients with candidemia caused by C. guilliermondii complex mainly had malignancy or central venous catheters. The isolates showed diminished susceptibility to fluconazole and echinocandins, but the low biofilm formation and low virulence in the G. mellonella model matched the good outcome of the patients infected by C. guilliermondii.

2016

Poster: 

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abstract No: 

#1354

Full conference title: 

26th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)