Rapid Development of Candida krusei Echinocandin Resistance during Caspofungin Therapy
ABSTRACTIn invasive candidiasis, there has been an epidemiological shift fromCandida albicansto non-albicansspecies infections, including infections withC. glabrata,C. parapsilosis,C. tropicalis, andC. krusei. Although the prevalence ofC. kruseiremains low among yeast infections, its intrinsic resistance to fluconazole raises epidemiological and therapeutic concerns. Echinocandins havein vitroactivity against mostCandidaspp. and are the first-line agents in the treatment of candidemia. Although resistance to echinocandin drugs is still rare, individual cases ofC. kruseiresistance have been reported in recent years, especially with strains that have been under selective pressure. A total of 15C. kruseistrains, 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 MICsin vitroand 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 inFKS1highlights the need to monitor the development of resistance inC. kruseiinfections treated with echinocandin drugs.