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Journal of Clinical Microbiology, September 2006, p. 3098-3104, Vol. 44, No. 9
0095-1137/06/$08.00+0     doi:10.1128/JCM.00665-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Multicenter Evaluation of the Etest and Disk Diffusion Methods for Differentiating Daptomycin-Susceptible from Non-Daptomycin-Susceptible Staphylococcus aureus Isolates

Laura A. Jevitt,1 Grace M. Thorne,2 Maria M. Traczewski,3 Ronald N. Jones,4 John E. McGowan Jr.,5 Fred C. Tenover,1* and Steven D. Brown3

Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,1 Cubist Pharmaceuticals, Lexington, Massachusetts 02421,2 Clinical Microbiology Institute, Wilsonville, Oregon 97070,3 JMI Laboratories, Inc., North Liberty, Iowa 52317,4 Rollins School of Public Health, Emory University, Atlanta, Georgia 303225

Received 28 March 2006/ Returned for modification 3 May 2006/ Accepted 26 June 2006

Daptomycin is a novel cyclic lipopeptide that is approved by the U.S. Food and Drug Administration for the treatment of complicated skin and skin structure infections associated with Staphylococcus aureus and other gram-positive pathogens and also staphylococcal bacteremia, including right-sided endocarditis. The Clinical and Laboratory Standards Institute (CLSI) established "susceptible-only" interpretive criteria for broth microdilution (BMD) and disk diffusion (DD) testing of daptomycin in 2005. However, a series of S. aureus isolates have been recovered with daptomycin MICs in the nonsusceptible range (i.e., MICs of >1 µg/ml). The objective of this study was to determine the ability of the Etest and DD methods to differentiate daptomycin-susceptible from nonsusceptible isolates of S. aureus compared to the results of the CLSI BMD reference method. There was a good correlation between Etest MIC results and the results of BMD among laboratories (r = 0.86 to 0.88), with 95.3% of the Etest MICs within a ±1 log2 dilution of the BMD MIC result. A total of 92 of 102 (90.2%) non-daptomycin-susceptible isolates of S. aureus identified by BMD in two participating laboratories were also classified as nonsusceptible by Etest. However, the very major and major error rates reported by one of the participating laboratories were 13.5 and 4.0%, respectively, primarily due to the absence of an intermediate category. The DD method, however, did not reliably differentiate daptomycin-susceptible from non-daptomycin-susceptible isolates. In 2005, daptomycin disks were voluntarily removed from the market by Cubist Pharmaceuticals. The disk diffusion breakpoints were subsequently removed from the CLSI M100 standard in 2006.

* Corresponding author. Mailing address: Division of Healthcare Quality Promotion (G-08), Centers for Disease Control and Prevention, 1600 Clifton Rd., NE, Atlanta, GA 30333. Phone: (404) 639-3375. Fax: (404) 639-1381. E-mail: fnt1{at}cdc.gov.

Journal of Clinical Microbiology, September 2006, p. 3098-3104, Vol. 44, No. 9
0095-1137/06/$08.00+0     doi:10.1128/JCM.00665-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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