Daptomycin susceptibility tests: interpretive criteria, quality control, and effect of calcium on in vitro tests

Daptomycin MICs were determined for 844 Gram-positive bacteria in three con centrations of Ca++ and compared with the MICs of vancomycin and teicoplani n. Daptomycin was twofold to fourfold more active against most species when tested in 50 mu g/ml of Ca++ than in 25 mu g/ml. In 50 mu g/ml of Ca++ dap tomycin was more active against methicillin-resistant staphylococci and van comycin-resistant enterococci than teicoplanin or vancomycin; 100% of these isolates were susceptible to less than or equal to 2.0 mu g/ml of daptomyc in. Different lots of Mueller-Hinton agar were variable in Ca++ content, an d daptomycin disk diffusion zone diameters were affected, i.e., zones were 1 to 15 mm smaller on one lot of agar with only 6 mu g/ml of Ca++ compared to another lot with 28 mu g/ml. The previously proposed daptomycin interpre tive breakpoints performed satisfactorily when MICs were determined in Muel ler-Hinton broth with 50 mu g/ml of Ca++ and when the agar gave appropriate zones with quality control strains. To define those control limits, replic ate tests with four quality control strains were performed in ten laborator ies using broth microdilution tests (with Ca++ supplemented broth) and disk diffusion tests on Mueller-Hinton agar without cation adjustments. (C) 200 0 Elsevier Science Inc. All rights reserved.