Molecular Analysis of Resistance and Detection of Non-Wild-Type Strains Using Etest Epidemiological Cutoff Values for Amphotericin B and Echinocandins for Bloodstream Candida Infections from a Tertiary Hospital in Qatar

Abstract

A total of 301 <i>Candida</i> bloodstream isolates collected from 289 patients over 5 years at a tertiary hospital in Qatar were evaluated. Out of all <i>Candida</i> infections, 53% were diagnosed in patients admitted to the intensive care units. Steady increases in non-<i>albicans Candida</i> species were reported from 2009 to 2014 (30.2% for <i>Candida albicans</i> versus 69.8% for the other <i>Candida</i> species). Etest antifungal susceptibility testing was performed on all recovered clinical isolates to determine echinocandin (micafungin and anidulafungin) and amphotericin B susceptibilities and assess non-wild-type (non-WT) strains (strains for which MICs were above the epidemiological cutoff values). DNA sequence analysis was performed on all isolates to assess the presence of <i>FKS</i> mutations, which confer echinocandin resistance in <i>Candida</i> species. A total of 3.9% of isolates (12/301) among strains of <i>C. albicans</i> and <i>C. orthopsilosis</i> contained <i>FKS</i> hot spot mutations, including heterozygous mutations in <i>FKS1</i> For <i>C. tropicalis</i>, the Etest appeared to overestimate strains non-WT for micafungin, anidulafungin, and amphotericin B, as 14%, 11%, and 35% of strains, respectively, had values above the epidemiological cutoff value. However, no <i>FKS</i> mutations were identified in this species. For all other species, micafungin best reported the echinocandin non-WT strains relative to the <i>FKS</i> genotype, as anidulafungin tended to overestimate non-wild-type strains. Besides <i>C. tropicalis</i>, few strains were classified as non-WT for amphotericin B.