Caspofungin MICs correlate with treatment outcomes among patients with Candida glabrata invasive candidiasis and prior echinocandin exposure.
Antimicrob Agents Chemother. 2013 May 13;
Authors: Shields RK, Nguyen MH, Press EG, Updike CA, Clancy CJ
Mutations in Candida glabrata FKS genes, which encode the echinocandin target enzyme, are independent risk factors for treatment failures during invasive candidiasis. We retrospectively compared the ability of caspofungin susceptibility testing methods to identify C. glabrata FKS mutant isolates and predict outcomes among patients at our center. Eight percent (10/120) of sterile-site C. glabrata isolates harbored FKS1 (n=3) or FKS2 (n=7) mutations, including 32% (10/32) recovered from patients with prior echinocandin exposure. Median echinocandin exposures for mutant and non-mutant isolates were 55 (range: 7-188) and 13 (3-84) days, respectively (p=0.004). Sensitivity/specificity of the CLSI caspofungin resistance breakpoint MIC (>0.12 μg/mL by broth microdilution (BMD) using RPMI medium) were 90% (9/10) and 3% (3/110) for identifying FKS mutants, respectively. Sensitivity/specificity of ROC curve-derived breakpoints by BMD-RPMI, BMD-antibiotic medium 3, Etest and YeastOne ranged from 70-100% and 89-95%, respectively; susceptibility rates varied between 83-90%. The 14-day echinocandin treatment success rate was 67% (44/66); failure was more likely with prior echinocandin exposure (p=0.002), infection with a FKS mutant (p=0.0001) or echinocandin-resistant isolates by BMD-AM3, Etest and YeastOne (p≤0.03). The failure rate among patients with prior exposure and infection with a resistant isolate was 91% (10/11), vs. 22% (12/55) among others (p<0.0001). In conclusion, ROC-derived caspofungin MIC breakpoints by several methods were sensitive and specific for identifying C. glabrata FKS mutant isolates. Mutations were seen exclusively among patients with prior echinocandin exposure. A paradigm that considers prior echinocandin exposure and caspofungin MICs accurately classified treatment outcomes for C. glabrata invasive candidiasis.
PMID: 23669387 [PubMed - as supplied by publisher]