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Antimicrobial Agents and Chemotherapy, February 2009, p. 805-807, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.01009-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Impact of Inoculum Size and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus (hVISA) on Vancomycin Activity and Emergence of VISA in an In Vitro Pharmacodynamic Model {triangledown}

Warren E. Rose,1,3,5 Steven N. Leonard,1,3 Kerri L. Rossi,1 Glenn W. Kaatz,2,4 and Michael J. Rybak1,2,3*

Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences,1 School of Medicine, Wayne State University, Detroit, Michigan 48201,2 Detroit Receiving Hospital, Detroit, Michigan 48201,3 John D. Dingell Department of Veteran's Affairs Medical Center, Detroit, Michigan 48201,4 University of Wisconsin School of Pharmacy, Madison, Wisconsin 537055

Received 28 July 2008/ Returned for modification 4 September 2008/ Accepted 11 November 2008

The activity of vancomycin against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and non-hVISA isolates, using an in vitro pharmacodynamic model, was reduced in the presence of a high inoculum amount (108 CFU/ml). A high bacterial load of >105 CFU/ml persisted for all strains with doses up to 5 g every 12 h against high inoculum amounts. No change in the vancomycin MIC was detected in any isolate at a moderate inoculum amount (106 CFU/ml), and bactericidal activity occurred only against the non-hVISA isolate (time to 99% kill, 7.5 h; P = 0.001).

* Corresponding author. Mailing address: Anti-Infective Research Laboratory, Pharmacy Practice 4148, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201. Phone: (313) 993-4673. Fax: (313) 577-8915. E-mail: m.rybak{at}wayne.edu

{triangledown} Published ahead of print on 17 November 2008.

Antimicrobial Agents and Chemotherapy, February 2009, p. 805-807, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.01009-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sader, H. S., Jones, R. N., Rossi, K. L., Rybak, M. J. (2009). Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate strains (hVISA) among Staphylococcus aureus causing bloodstream infections in nine USA hospitals. J Antimicrob Chemother 64: 1024-1028 [Abstract] [Full Text]  
  • Zhanel, G. G., Voth, D., Nichol, K., Karlowsky, J. A., Noreddin, A. M., Hoban, D. J. (2009). Pharmacodynamic activity of ceftobiprole compared with vancomycin versus methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) using an in vitro model. J Antimicrob Chemother 64: 364-369 [Abstract] [Full Text]  


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