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Antimicrobial Agents and Chemotherapy, July 2009, p. 2928-2933, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01544-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Activity of Telavancin against Staphylococcus aureus Strains with Various Vancomycin Susceptibilities in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations {triangledown}

Steven N. Leonard,1,3,4 Céline Vidaillac,1 and Michael J. Rybak1,2,3*

Anti-Infective Research Laboratory, 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 Northeastern University, School of Pharmacy, Boston, Massachusetts 021154

Received 19 November 2008/ Returned for modification 23 March 2009/ Accepted 26 April 2009

We investigated the activity of telavancin, a novel lipoglycopeptide, alone and combined with gentamicin or rifampin (rifampicin) against strains of Staphylococcus aureus with various vancomycin susceptibilities. Strains tested included methicillin (meticillin)-resistant S. aureus (MRSA) 494, methicillin-sensitive S. aureus (MSSA) 1199, heteroresistant glycopeptide-intermediate S. aureus (hGISA) 1629, which was confirmed by a population analysis profile, and glycopeptide-intermediate S. aureus (GISA) NJ 992. Regimens of 10 mg/kg telavancin daily and 1 g vancomycin every 12 h were investigated alone and combined with 5 mg/kg gentamicin daily or 300 mg rifampin every 8 h in an in vitro model with simulated endocardial vegetations over 96 h. Telavancin demonstrated significantly greater killing than did vancomycin (P < 0.01) for all isolates except MRSA 494 (P = 0.07). Telavancin absolute reductions, in log10 CFU/g, at 96 h were 2.8 ± 0.5 for MRSA 494, 2.8 ± 0.3 for MSSA 1199, 4.2 ± 0.2 for hGISA 1629, and 4.1 ± 0.3 for GISA NJ 992. Combinations of telavancin with gentamicin significantly enhanced killing compared to telavancin alone against all isolates (P < 0.001) except MRSA 494 (P = 0.176). This enhancement was most evident against hGISA 1629, where killing to the level of detection (2 log10 CFU/g) was achieved at 48 h (P < 0.001). The addition of rifampin to telavancin resulted in significant (P < 0.001) enhancement of killing against only MSSA 1199. No changes in telavancin susceptibilities were observed. These results suggest that telavancin may have therapeutic potential, especially against strains with reduced susceptibility to vancomycin. Combination therapy, particularly with gentamicin, may improve bacterial killing against certain strains.

* 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) 577-4376. Fax: (313) 577-8915. E-mail: m.rybak{at}wayne.edu

{triangledown} Published ahead of print on 4 May 2009.

Antimicrobial Agents and Chemotherapy, July 2009, p. 2928-2933, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01544-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vidaillac, C., Leonard, S. N., Rybak, M. J. (2009). In Vitro Activity of Ceftaroline against Methicillin-Resistant Staphylococcus aureus and Heterogeneous Vancomycin-Intermediate S. aureus in a Hollow Fiber Model. Antimicrob. Agents Chemother. 53: 4712-4717 [Abstract] [Full Text]  


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