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It has been argued that thein vitro activity of caspofungin (CSP) is not a good predictor of the outcome of echinocandin treatmentin vivo . We evaluated thein vitro activity of CSP and the presence ofFKS mutations in the hot spot 1 (HS1) region of theFKS1 andFKS2 genes in 17 Candida glabrata strains with a wide range of MICs. The efficacy of CSP against systemic infections from each of the 17 strains was evaluated in a murine model. No HS1 mutations were found in the eight strains showing MICs for CSP of ≤0.5 μg/ml, but they were present in eight of the nine strains with MICs of ≥1 μg/ml, i.e., three in theFKS1 gene and five in theFKS2 gene. CSP was effective for treating mice infected with strains with MICs of ≤0.5 μg/ml, showed variable efficacy in animals challenged with strains with MICs of 1 μg/ml, and did not work in those with strains with MICs of &gt;1 μg/ml. In addition, mutations, including one reported for the first time, were found outside the HS1 region in theFKS2 gene of six strains with different MICs, but their presence did not influence drug efficacy. Thein vitro activity of CSP was compared with that of another echinocandin, anidulafungin, suggesting that the MICs of both drugs, as well as mutations in the HS1 regions of theFKS1 andFKS2 genes, are predictive of outcome.

antimicrobial agents and chemotherapy

<i>In Vitro</i> Antifungal Susceptibility of Candida glabrata to Caspofungin and the Presence of <i>FKS</i> Mutations Correlate with Treatment Response in an Immunocompromised Murine Model of Invasive Infection

In Vitro Antifungal Susceptibility of Candida glabrata to Caspofungin and the Presence of FKS Mutations Correlate with Treatment Response in an Immunocompromised Murine Model of Invasive Infection