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Rapid Evolution of Multidrug Resistance in a Candida lusitaniae Infection during Micafungin Monotherapy.
Scott, Nancy E; Edwin Erayil, Serin; Kline, Susan E; Selmecki, Anna.
Afiliación
  • Scott NE; University of Minnesota, Bioinformatics and Computational Biology Program, Minneapolis, Minnesota, USA.
  • Edwin Erayil S; University of Minnesota, Department of Microbiology and Immunology, Minneapolis, Minnesota, USA.
  • Kline SE; University of Minnesota Medical School, Department of Medicine, Division of Infectious Diseases and International Medicine, Minneapolis, Minnesota, USA.
  • Selmecki A; University of Minnesota Medical School, Department of Medicine, Division of Infectious Diseases and International Medicine, Minneapolis, Minnesota, USA.
Antimicrob Agents Chemother ; 67(8): e0054323, 2023 08 17.
Article en En | MEDLINE | ID: mdl-37428075
Candida (Clavispora) lusitaniae is a rare, emerging non-albicans Candida species that can cause life-threatening invasive infections, spread within hospital settings, and rapidly acquire antifungal drug resistance, including multidrug resistance. The frequency and spectrum of mutations causing antifungal drug resistance in C. lusitaniae are poorly understood. Analyses of serial clinical isolates of any Candida species are uncommon and often analyze a limited number of samples collected over months of antifungal therapy with multiple drug classes, limiting the ability to understand relationships between drug classes and specific mutations. Here, we performed comparative genomic and phenotypic analysis of 20 serial C. lusitaniae bloodstream isolates collected daily from an individual patient treated with micafungin monotherapy during a single 11-day hospital admission. We identified isolates with decreased micafungin susceptibility 4 days after initiation of antifungal therapy and a single isolate with increased cross-resistance to micafungin and fluconazole, despite no history of azole therapy in this patient. Only 14 unique single nucleotide polymorphisms (SNPs) were identified between all 20 samples, including three different FKS1 alleles among isolates with decreased micafungin susceptibility and an ERG3 missense mutation found only in the isolate with increased cross-resistance to both micafungin and fluconazole. This is the first clinical evidence of an ERG3 mutation in C. lusitaniae that occurred during echinocandin monotherapy and is associated with cross-resistance to multiple drug classes. Overall, the evolution of multidrug resistance in C. lusitaniae is rapid and can emerge during treatment with only first-line antifungal therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candidiasis / Antifúngicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candidiasis / Antifúngicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Antimicrob Agents Chemother Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos