Low Level of Antifungal Resistance in Iranian Isolates of Candida glabrata Recovered from Blood Samples in a Multicenter Study from 2015 to 2018 and Potential Prognostic Values of Genotyping and Sequencing of <i>PDR1</i>

Abstract

Establishing an effective empirical antifungal therapy requires that national surveillance studies be conducted. Herein, we report the clinical outcome of infections with and the microbiological features of Iranian isolates of <i>Candida</i><i>glabrata</i> derived from patients suffering from candidemia. <i>C. glabrata</i> isolates were retrospectively collected from four major cities in Iran; identified by a 21-plex PCR, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and large subunit of ribosomal DNA sequencing; and genotyped by amplified fragment length polymorphism (AFLP). Mutations in <i>PDR1</i>, <i>ERG11</i>, and hot spot 1 (HS1) of <i>FKS1</i> and <i>FKS2</i> were investigated, and antifungal susceptibility testing (AFST) was performed (by the CLSI M27-A3 and M27-S4 methods). Seventy isolates of <i>C. glabrata</i> were collected from 65 patients with a median age of 58 years. Fluconazole was the most widely used (29.23%) 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 the isolates were non-wild type (non-WT) for susceptibility to caspofungin and voriconazole, respectively. All isolates showed the WT phenotype for amphotericin B, posaconazole, and itraconazole. HS1 of <i>FKS1</i> and <i>FKS2</i> did not harbor any mutations, while numerous missense mutations were observed in <i>PDR1</i> and <i>ERG11</i> AFLP clustered our isolates into nine genotypes; among them, genotypes 1 and 2 were significantly associated with a higher mortality rate (<i>P</i> = 0.034 and <i>P</i> = 0.022, α < 0.05). Moreover, 83.3% of patients infected with strains harboring a single new mutation in <i>PDR1</i>, T745A, died despite treatment with fluconazole or caspofungin. Overall, Iranian isolates of <i>C. glabrata</i> were susceptible to the major antifungal drugs. Application of genotyping techniques and sequencing of a specific gene (<i>PDR1</i>) might have prognostic implications.