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Antimicrobial Agents and Chemotherapy, September 2007, p. 3311-3316, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.01470-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pharmacodynamic Effects of Telavancin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Strains in the Presence of Human Albumin or Serum and in an In Vitro Kinetic Model{triangledown}

Inga Odenholt,1,2* Elisabeth Löwdin,2 and Otto Cars2

Infectious Diseases Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden,1 Antibiotic Research Unit, Sections of Infectious Diseases and Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden2

Received 23 November 2006/ Returned for modification 9 April 2007/ Accepted 2 July 2007

Telavancin is a novel bactericidal lipoglycopeptide with multiple mechanisms of action against gram-positive pathogens. The aim of this study was to describe the dynamics of the antimicrobial effect of telavancin against two strains of Staphylococcus aureus (methicillin susceptible and methicillin resistant) in an in vitro kinetic model with simulated human pharmacokinetics. Also, static experiments were performed to determine the rate and extent of killing by telavancin in the presence and absence of human albumin and human serum. Experiments in broth and in nutrient-depleted medium were performed to study the rate and extent of killing by telavancin of bacteria in different growth phases. In the in vitro kinetic model regrowth was noted at 24 h for both strains when exposed to initial concentrations below 5 mg/liter. There was a >3-log10 killing at all concentrations from 0.5x MIC and above at 24 h both in broth and in the presence of 40-g/liter human albumin. In contrast to the methicillin-susceptible strain, the methicillin-resistant strain in 40-g/liter human albumin showed a regrowth at concentrations of 0.5x MIC and 1x MIC at 24 h. At all the other concentrations >3-log10 killing was seen at 24 h. Concordant results were seen in 50% human serum. At a target area under the curve/MIC ratio of 50 (corresponding to the human dose of 10 mg/kg of body weight, administered intravenously), >3-log10 killing was observed at 6 to 8 h. Unlike most antibiotics, telavancin was able to kill both strains in a nongrowing phase.

* Corresponding author. Mailing address: Department of Infectious Diseases, University Hospital MAS, S-205 02 Malmö, Sweden. Phone: 46 40-331806. Fax: 46 40-336279. E-mail: inga.odenholt{at}med.lu.se

{triangledown} Published ahead of print on 9 July 2007.

Antimicrobial Agents and Chemotherapy, September 2007, p. 3311-3316, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.01470-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • LaPlante, K. L., Mermel, L. A. (2009). In Vitro Activities of Telavancin and Vancomycin against Biofilm-Producing Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis Strains. Antimicrob. Agents Chemother. 53: 3166-3169 [Abstract] [Full Text]  
  • Charneski, L., Patel, P. N, Sym, D. (2009). Telavancin: A Novel Lipoglycopeptide Antibiotic. The Annals of Pharmacotherapy 43: 928-938 [Abstract] [Full Text]  
  • Lubenko, I. Yu., Strukova, E. V., Smirnova, M. V., Vostrov, S. N., Portnoy, Y. A., Zinner, S. H., Firsov, A. A. (2008). Telavancin and vancomycin pharmacodynamics with Staphylococcus aureus in an in vitro dynamic model. J Antimicrob Chemother 62: 1065-1069 [Abstract] [Full Text]  


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