Recent Increase in the Prevalence of Fluconazole-Non-susceptible Candida tropicalis Blood Isolates in Turkey: Clinical Implication of Azole-Non-susceptible and Fluconazole Tolerant Phenotypes and Genotyping

Abstract

<i>Candida tropicalis</i> is the fourth leading cause of candidemia in Turkey. Although <i>C. tropicalis</i> isolates from 1997 to 2017 were characterized as fully susceptible to antifungals, the increasing global prevalence of azole-non-susceptible (ANS) <i>C. tropicalis</i> and the association between high fluconazole tolerance (HFT) and fluconazole therapeutic failure (FTF) prompted us to re-evaluate azole susceptibility of <i>C. tropicalis</i> in Turkey. In this study, 161 <i>C. tropicalis</i> blood isolates from seven clinical centers were identified by ITS rDNA sequencing, genotyped by multilocus microsatellite typing, and tested for susceptibility to five azoles, two echinocandins, and amphotericin B (AMB); antifungal resistance mechanisms were assessed by sequencing of <i>ERG11</i> and <i>FKS1</i> genes. The results indicated that <i>C. tropicalis</i> isolates, which belonged to 125 genotypes grouped into 11 clusters, were fully susceptible to echinocandins and AMB; however, 18.6% of them had the ANS phenotype but only two carried the ANS-conferring mutation (Y132F). HFT was recorded in 52 isolates, 10 of which were also ANS. Large proportions of patients infected with ANS and HFT isolates (89 and 40.7%, respectively) showed FTF. Patients infected with azole-susceptible or ANS isolates did not differ in mortality, which, however, was significantly lower for those infected with HFT isolates (<i>P</i> = 0.007). There were significant differences in mortality (<i>P</i> = 0.02), ANS (<i>P</i> = 0.012), and HFT (<i>P</i> = 0.007) among genotype clusters. The alarming increase in the prevalence of <i>C. tropicalis</i> blood isolates with ANS and HFT in Turkey and the notable FTF rate should be a matter of public health concern.