Clonal spread in Candida glabrata bloodstream isolates and fluconazole resistance affected by prolonged exposure: a 12-year single-center study in Belgium [PublishAheadOfPrint]

Candida glabrata is a major cause of candidemia in immunocompromised patients and is characterized by a high-level of fluconazole resistance. In the present study, acquisition of antifungal resistance and potential clonal spread of C. glabrata were explored at a single center over a 12-year period by analyzing 187 independent clinical C. glabrata bloodstream isolates. One strain was found to be micafungin resistant due to a mutation in the FKS2 gene. Fluconazole resistance remained stable throughout the period and was observed in 20 (10.7%) of the isolates. Analysis of the antifungal consumption data revealed that recent prior exposure to fluconazole increased the risk to be infected by a resistant strain. In particular, the duration of the treatment was significantly longer for patients infected by a resistant isolate while total and mean daily doses received did not impact the acquisition of resistance in C. glabrata. No link between genotype and resistance was found. However, multilocus variable-number tandem-repeat analyses indicated a potential intra-hospital spread of some isolates between patients. These isolates shared the same genetic profile and infected patients were hospitalized in the same unit during an overlapping period. Finally, quantitative real-time PCR analyses showed that, unlike other ABC efflux pumps, CgCDR1 was significantly more expressed in resistant strains, suggesting that it would be more involved in FLC resistance. Our study provides additional evidence that a proper administration of fluconazole is required to limit resistance and that strict hand hygiene is necessary to avoid possible spreading of C. glabrata isolates between patients.

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