Rapid development of Candida krusei echinocandin resistance during caspofungin therapy.
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.
Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
A
A
Forastiero
Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
V
V
Garcia-Gil
Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
O
O
Rivero-Menendez
Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
R
R
Garcia-Rubio
Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
M C
MC
Monteiro
Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
A
A
Alastruey-Izquierdo
Infectious Diseases Department, Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
R
R
Jordan
Mycology Laboratory, Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
I
I
Agorio
Mycology Reference Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain emellado@isciii.es.
E
E
Mellado
D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D000077336:Caspofungin; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D055666:Lipopeptides; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin