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Antimicrob. Agents Chemother. doi:10.1128/AAC.01009-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Impact of inoculum and heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) on vancomycin activity and emergence of VISA in an in vitro pharmacodynamic model

Warren E. Rose, Steven N. Leonard, Kerri L. Rossi, Glenn W. Kaatz, and Michael J. Rybak*

Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, and School of Medicine, Wayne State University, Detroit, MI USA, 48201; Detroit Receiving Hospital, Detroit, MI, USA, 48201; John D. Dingell Department of Veteran's Affairs Medical Center, Detroit, MI USA 48201; University of Wisconsin School of Pharmacy, Madison, WI 53705


   Abstract

The activity of vancomycin against hVISA and non-hVISA isolates was reduced in the presence of a high inoculum (108 CFU/ml) using an in vitro pharmacodynamic model. A high bacterial load of > 105 CFU/mL persisted in all strains with doses up to 5 g every 12 h against high inoculum. No change in vancomycin MIC was detected in any isolate at moderate inoculum (106 CFU/ml) and bactericidal activity occurred only in the non-hVISA (T99 7.5 h; p=0.001)







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