期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 59, 期 11, 页码 6975-6982出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01005-15
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资金
- Spanish Fondode Investigacion Sanitaria (FIS) [PI12_02376]
- Instituto de Salud Carlos III
- Subdireccion General de Redes y Centros de Investigacion Cooperativa
- Ministerio de Economia y Competitividad
- Spanish Network for Research in Infectious Diseases [REIPI RD 12/0015]
- Spanish Fondo de Investigacion Sanitaria through a Sara Borrell Fellowship [CD13/00198]
In invasive candidiasis, there has been an epidemiological shift from Candida albicans to non-albicans species infections, including infections with C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. Although the prevalence of C. krusei remains low among yeast infections, its intrinsic resistance to fluconazole raises epidemiological and therapeutic concerns. Echinocandins have in vitro activity against most Candida spp. and are the first-line agents in the treatment of candidemia. Although resistance to echinocandin drugs is still rare, individual cases of C. krusei resistance have been reported in recent years, especially with strains that have been under selective pressure. A total of 15 C. krusei strains, isolated from the blood, urine, and soft tissue of an acute lymphocytic leukemia patient, were analyzed. Strains developed echinocandin resistance during 10 days of caspofungin therapy. The molecular epidemiology of the isolates was investigated using two different typing methods: PCR-based amplification of the species-specific repetitive polymorphic CKRS-1 sequence and multilocus sequence typing. All isolates were genetically related, and the mechanism involved in decreased echinocandin susceptibility was characterized. Clinical resistance was associated with an increase in echinocandin MICs in vitro and was related to three different mutations in hot spot 1 of the target enzyme Fks1p. Molecular evidence of the rapid acquisition of resistance by different mutations in FKS1 highlights the need to monitor the development of resistance in C. krusei infections treated with echinocandin drugs.
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