Candida guilliermondii Complex Is Characterized by High Antifungal Resistance but Low Mortality in 22 Cases of Candidemia

Abstract

The objectives of our study were to describe the characteristics of patients with Candida guilliermondii candidemia and to perform an in-depth microbiological characterization of isolates and compare them with those of patients with C. albicans candidemia. We described the risk factors and outcomes of 22 patients with candidemia caused by the C. guilliermondii complex. Incident isolates were identified using molecular techniques, and susceptibility to fluconazole, anidulafungin, and micafungin was studied. Biofilm formation was measured using the crystal violet assay (biomass production) and the XTT reduction assay (metabolic activity), and virulence was studied using the Galleria mellonella model. Biofilm formation was compared with that observed for C. albicans. The main conditions predisposing to infection were malignancy (68%), immunosuppressive therapy (59%), and neutropenia (18%). Clinical presentation of candidemia was less severe in patients infected by the C. guilliermondii complex than in patients infected by C. albicans, and 30-day mortality was lower in C. guilliermondii patients (13.6% versus 33.9%, respectively; P ϭ 0.049). Isolates were identified as C. guilliermondii sensu stricto (n ϭ 17) and Candida fermentati (n ϭ 5). The isolates produced biofilms with low metabolic activity and moderate biomass. The G. mellonella model showed that C. guilliermondii was less virulent than C. albicans (mean of 6 days versus 1 day of survival, respectively; P Ͻ 0.001). Patients with candidemia caused by the C. guilliermondii complex had severe and debilitating underlying conditions. Overall, the isolates showed diminished susceptibility to fluconazole and echinocandins, although poor biofilm formation and the low virulence were associated with a favorable outcome.

Candidemia due to Candida guilliermondii in an immuno-compromised infant: a case report and review of literature

“…However, recently, there is an increasing number of reports regarding the bloodstream infections due to this complex [4]. In addition, due to resistance or decreased susceptibility to antifungal agents, C. guilliermondii complex has been proposed to be a re-emerging pathogen in high-risk patients.…”

“…In addition, the decreased susceptibility of this pathogenic yeast to fluconazole has been observed in different geographical areas [1-4]. However, the epidemiology of candidemia due to C. guilliermondii has been underestimated so far.…”

Different detection capabilities by mycological media for Candida isolates from mono- or dual-species cultures

“…We used each isolate to prepare a 0.5 McFarland suspension (~10 6 CFU/mL) in phosphate-buffered saline. Using a checkerboard-like dilution scheme (see online supplementary figure S1), we mixed (ratio 1:1) each isolate’s suspension with the suspension of itself or with the suspension of each other isolate, respectively, in 96-well cell culture polystyrene plates to reach a final concentration of ~500 CFU per well.…”

“…4 However, the gamut of clinically relevant Candida species is expanding 5 and, notably, less common species (i.e. Candida guilliermondii complex), 6 rare species (e.g. Candida inconspicua [ Torulopsis inconspicua ], Candida pararugosa and Pichia norvegensis [ Candida norvegensis ]), 7 or emerging species (i.e.…”

“…Candida auris ) 8 may exhibit high antifungal resistance levels, thereby compromising infection outcomes. Furthermore, mixed bloodstream infections with Candida species in single patient-episodes are not uncommon, 6,9 consequently leading to misdiagnoses because of apparently pure isolates in mycological cultures.…”