Low level of antifungal resistance in Iranian isolates of Candida glabrata recovered from blood samples from multicenter (2015-2018): Potential prognostic values of genotyping and sequencing of PDR1

Abstract

Establishing an effective empirical antifungal therapy requires conducting national surveillance studies. Herein, we report the clinical outcome and microbiological features of Iranian isolates of C. glabrata derived from patients suffering from candidemia. C. glabrata isolates were retrospectively collected from four major cities of Iran, identified by a 21-plex PCR, MALDI-TOF MS, and LSU rDNA sequencing, and genotyped by Amplified fragment length polymorphism (AFLP). Mutations in PDR1, ERG11, and hotspot1 of FKS1 and FKS2, were investigated, and antifungal susceptibility testing (AFST) was performed (CLSI M27-A3/S4). Seventy isolates of C. glabrata were collected from 65 patients with median age of 58. Fluconazole (29.23) was the most widely used and least effective antifungal agent. The overall crude mortality rate was 35.4. Only one strain was resistant to fluconazole and 57.7 and 37.5 of isolates were non-wild type (non-WT) against caspofungin and voriconazole, respectively. All of isolates showed WT phenotype for AMB, posaconazole, and itraconazole. HS1 of FKS1 and FKS2 did not harbor any mutations, while numerous missense mutations were observed in PDR1 and ERG11 AFLP clustered our isolates into nine genotypes, among them genotypes 1 and 2 were significantly associated with a higher mortality rate (P=0.034 and P=0.022, alpha<0.05). Moreover, 83.3 of patients infected with strains harboring a single new mutation of T745A in PDR1 died despite of treatment with fluconazole or caspofungin. Overall, Iranian isolates of C. glabrata were susceptible to major antifungal drugs. Application of genotyping techniques and sequencing of specific genes, PDR1, might have prognostic implications.