Showing papers by "Suhail Ahmad published in 2023"

Strategies to Prevent Transmission of Candida auris in Healthcare Settings

Abstract: Candida auris, a recently recognized yeast pathogen, has become a major public health threat due to the problems associated with its accurate identification, intrinsic and acquired resistance to antifungal drugs, and its potential to easily contaminate the environment causing clonal outbreaks in healthcare facilities. These outbreaks are associated with high mortality rates particularly among older patients with multiple comorbidities under intensive care settings. The purpose of this review is to highlight strategies that are being adapted to prevent transmission of C. auris in healthcare settings. Colonized patients shed C. auris into their environment which contaminates surrounding equipment. It resists elimination even by robust decontamination procedures and is easily transmitted to new patients during close contact resulting in outbreaks. Efforts are being made to rapidly identify C. auris-infected/C. auris-colonized patients, to determine its susceptibility to antifungals, and to perform effective cleaning and decontamination of the environment and isolation of colonized patients to prevent further transmission. Rapid and accurate identification of hospitalized patients infected/colonized with C. auris, rapid detection of its susceptibility patterns, and appropriate use of infection control measures can help to contain the spread of this highly pathogenic yeast in healthcare settings and prevent/control outbreaks.

Molecular Characterization and Sterol Profiles Identify Nonsynonymous Mutations in ERG2 as a Major Mechanism Conferring Reduced Susceptibility to Amphotericin B in Candida kefyr

Abstract: Some yeast species exhibit intrinsic resistance or rapidly acquire resistance to azole antifungals. Despite >50 years of clinical use, resistance to amphotericin B (AMB) among yeast species has been extremely rarely reported until recently. ABSTRACT The molecular basis of reduced susceptibility to amphotericin B (rs-AMB) among any yeasts is poorly defined. Genetic alterations in genes involved in ergosterol biosynthesis and total cell sterols were investigated among clinical Candida kefyr isolates. C. kefyr isolates (n = 81) obtained from 74 patients in Kuwait and identified by phenotypic and molecular methods were analyzed. An Etest was initially used to identify isolates with rs-AMB. Specific mutations in ERG2 and ERG6 involved in ergosterol biosynthesis were detected by PCR sequencing. Twelve selected isolates were also tested by the SensiTitre Yeast One (SYO), and total cell sterols were evaluated by gas chromatography-mass spectrometry and ERG3 and ERG11 sequencing. Eight isolates from 8 patients showed rs-AMB by Etest, including 2 isolates with additional resistance to fluconazole or to all three antifungals. SYO correctly identified 8 of 8 rs-AMB isolates. A nonsynonymous mutation in ERG2 was detected in 6 of 8 rs-AMB isolates but also in 3 of 73 isolates with a wild-type AMB pattern. One rs-AMB isolate contained a deletion (frameshift) mutation in ERG2. One or more nonsynonymous mutations was detected in ERG6 in 11 of 81 isolates with the rs-AMB or wild-type AMB pattern. Among 12 selected isolates, 2 and 2 isolates contained a nonsynonymous mutation(s) in ERG3 and ERG11, respectively. Ergosterol was undetectable in 7 of 8 rs-AMB isolates, and the total cell sterol profiles were consistent with loss of ERG2 function in 6 rs-AMB isolates and loss of ERG3 activity in another rs-AMB isolate. Our data showed that ERG2 is a major target conferring rs-AMB in clinical C. kefyr isolates. IMPORTANCE Some yeast species exhibit intrinsic resistance or rapidly acquire resistance to azole antifungals. Despite >50 years of clinical use, resistance to amphotericin B (AMB) among yeast species has been extremely rarely reported until recently. Reduced susceptibility to AMB (rs-AMB) among yeast species is, therefore, a matter of serious concern due to the availability of only four classes of antifungal drugs. Recent studies in Candida glabrata, Candida lusitaniae, and Candida auris have identified ERG genes involved in ergosterol biosynthesis as the major targets conferring rs-AMB. The results of this study also show that nonsynonymous mutations in ERG2 impair its function, abolish ergosterol from C. kefyr, and confer rs-AMB. Thus, rapid detection of rs-AMB among clinical isolates will help in proper management of invasive C. kefyr infections.