Increasing Echinocandin Resistance in Candida glabrata: Clinical Failure Correlates with Presence of FKS Mutations and Elevated MIC.
Clin Infect Dis. 2013 Mar 13;
Authors: Alexander BD, Johnson MD, Pfeiffer CD, Jiménez-Ortigosa C, Catania J, Booker R, Castanheira M, Messer SA, Perlin DS, Pfaller MA
Background. Fluconazole (FLC) resistance is common in C. glabrata and echinocandins are often used as first line therapy. Resistance to echinocandin therapy has been associated with FKS1 and FKS2 gene alterations. Methods. We reviewed records of all patients with C. glabrata bloodstream infection at Duke Hospital over the past decade (2001-10) and correlated treatment outcome with MIC results and the presence of FKS gene mutations. For each isolate, MICs to FLC and echinocandins (anidulafungin [ANF], caspofungin [CSF], and micafungin [MCF]) and FKS1 and FKS2 gene sequences were determined. Results. Two hundred ninety-three episodes (313 isolates) of C. glabrata bloodstream infection were analyzed. Resistance to echinocandins increased from 4.9% to 12.3% and to FLC from 18% to 30% between 2001 and 2010, respectfully. Among the 78 FLC resistant isolates, 14.1% were resistant to one or more echinocandins. Twenty-five (7.9%) isolates harbored a FKS mutation. The predictor of a FKS mutant strain was prior echinocandin therapy (stepwise multivariable analysis, OR 19.647, 95% CI 7.19-58.1). Eighty percent (8/10) of patients infected with FKS mutants demonstrating intermediate or resistant MICs to an echinocandin and treated with an echinocandin failed to respond or responded initially but recurred. Conclusions. Echinocandin resistance is increasing, including among FLC resistant isolates. The new CLSI clinical breakpoints differentiate wild-type from C. glabrata strains bearing clinically significant FKS1/FKS2 mutations. These observations underscore the importance of knowing the local epidemiology and resistance patterns for Candida within institutions and susceptibility testing of echinocandins for C. glabrata to guide therapeutic decision making.
PMID: 23487382 [PubMed - as supplied by publisher]