We determined the echinocandin minimum effective concentration (MEC) values for caspofungin, micafungin and anidulafungin against 288 Aspergillus isolates prospectively collected from transplant patients with proven or probable invasive aspergillosis between 2001 and 2006 as part of the Transplant-Associated Infection Surveillance Network (TRANSNET). We demonstrated that the vast majority of Aspergillus isolates had MEC values at or below the epidemiological cutoff values for caspofungin, micafungin and anidulafungin, even from patients who had received caspofungin.

Candida glabrata is the second leading cause of candidemia in the United States. Its high resistance to triazole antifungal drugs has led to the increased use of the echinocandin class of antifungal agents for primary therapy of these infections. We monitored C. glabrata bloodstream isolates from a population-based surveillance for elevated echinocandin MIC values (MIC ≥0.25 mug/ml). From the 490 C. glabrata isolates that were screened, we identified 16 isolates with an elevated MIC value (2.9% of isolates from Atlanta and 2.0% of isolates from Baltimore) to one or more of the echinocandin drugs caspofungin, anidulafungin or micafungin. All the isolates with elevated MIC values had a mutation in the previously identified hotspot 1 of either glucan synthase FKS1 (n=2) or FKS2 (n=14) genes. No mutations were detected in hotspot 2 of either FKS1 or FKS2. The predominant mutation was FKS2 serine 663 to proline (S663P), found in 10 of the isolates with elevated echinocandin MICs. Two of the mutations, R631G in FKS1 and R665G in FKS2 have not been previously reported for C. glabrata. Multilocus sequence typing indicated that the predominance of the S663P mutation was not due to the clonal spread of a single sequence type. With a rising number of echinocandin therapy failures reported, it is important to continue to monitor rates of elevated echinocandin MIC values and the associated mutations.