Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida Time for harmonization of CLSI and EUCAST broth microdilution methods

Background Both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) have MIC clinical breakpoints (CBPs) for fluconazole (FLU) and Candida EUCAST CBPs are species specific and apply only to C albicans C tropicalis and C parapsilosis while CLSI CBPs apply to all species We reassessed the CLSI CBPs for FLU and Candida in light of recent data Methods We examined (1) molecular mechanisms of resistance and cross resistance profiles (2) wild type (WT)MICs and epidemiological cutoff values (ECVs) for FLU and major Candida species by both CLSI and EUCAST methods (3) determination of essential (EA) and categorical agreement (CA) between CLSI and EUCAST methods (4) correlation of MICs with outcomes from previously published data using CLSI and EUCAST methods and (5) pharmacokinetic and pharmacodynamic considerations We applied these findings to propose new species specific CLSI CBPs for FLU and Candida Results WT distributions from large collections of Candida revealed similar ECVs by both CLSI and EUCAST methods (0 5-1 mcg/ml for C albicans 2 mcg/ml for C parapsilosis and C tropicalis 32 mcg/ml for C glabrata and 64-128 for C krusei) Comparison of CLSI and EUCAST MICs reveal EA and CA of 95% and 96% respectively Datasets correlating CLSI and EUCAST FLU MICs with outcomes revealed decreased response rates when MICs were >4 mcg/ml for C albicans C tropicalis and C parapsilosis and >16 mcg/ml for C glabrata Conclusions Adjusted CLSI CBPs for FLU and C albicans C parapsilosis C tropicalis CS <= 2 mcg/ml SDD 4 mcg/ml R >= 8 mcg/ml) and C glabrata (SDD <= 32 mcg/ml R >= 64 mcg/ml) should be more sensitive for detecting emerging resistance among common Candida species and provide consistency with EUCAST CBPs (C) 2010 Elsevier Ltd All rights reserved