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Antimicrobial Agents and Chemotherapy, March 2009, p. 918-925, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00766-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Oritavancin Kills Stationary-Phase and Biofilm Staphylococcus aureus Cells In Vitro {triangledown}

Adam Belley,1 Eve Neesham-Grenon,1 Geoffrey McKay,1 Francis F. Arhin,1 Robert Harris,2,3 Terry Beveridge,2,4 Thomas R. Parr Jr.,1 and Gregory Moeck1*

Targanta Therapeutics Incorporated, 7170 Frederick Banting, St. Laurent, Quebec H4S 2A1, Canada,1 MicroTEM Inc., P.O. Box 1107, 101 Chalmers St., Elora, Ontario N0B 1S0, Canada,2 Guelph Regional Integrated Imaging Facility, New Science Complex, 488 Gordon St., University of Guelph, Guelph, Ontario N1G 2W1, Canada,3 Department of Molecular and Cellular Biology, New Science Complex, 488 Gordon St., University of Guelph, Guelph, Ontario N1G 2W1, Canada4

Received 12 June 2008/ Returned for modification 19 October 2008/ Accepted 11 December 2008

Slow-growing bacteria and biofilms are notoriously tolerant to antibiotics. Oritavancin is a lipoglycopeptide with multiple mechanisms of action that contribute to its bactericidal action against exponentially growing gram-positive pathogens, including the inhibition of cell wall synthesis and perturbation of membrane barrier function. We sought to determine whether oritavancin could eradicate cells known to be tolerant to many antimicrobial agents, that is, stationary-phase and biofilm cultures of Staphylococcus aureus in vitro. Oritavancin exhibited concentration-dependent bactericidal activity against stationary-phase inocula of methicillin-susceptible S. aureus (MSSA) ATCC 29213, methicillin-resistant S. aureus (MRSA) ATCC 33591, and vancomycin-resistant S. aureus (VRSA) VRS5 inoculated into nutrient-depleted cation-adjusted Mueller-Hinton broth. As has been described for exponential-phase cells, oritavancin induced membrane depolarization, increased membrane permeability, and caused ultrastructural defects including a loss of nascent septal cross walls in stationary-phase MSSA. Furthermore, oritavancin sterilized biofilms of MSSA, MRSA, and VRSA at minimal biofilm eradication concentrations (MBECs) of between 0.5 and 8 µg/ml. Importantly, MBECs for oritavancin were within 1 doubling dilution of their respective planktonic broth MICs, highlighting the potency of oritavancin against biofilms. These results demonstrate a significant activity of oritavancin against S. aureus in phases of growth that exhibit tolerance to other antimicrobial agents.

* Corresponding author. Mailing address: Targanta Therapeutics Incorporated, 7170 Frederick Banting, St. Laurent, Quebec H4S 2A1, Canada. Phone: (514) 332-1008, ext. 232. Fax: (514) 332-6033. E-mail: gmoeck{at}targanta.com

{triangledown} Published ahead of print on 22 December 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 918-925, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.00766-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Arhin, F. F., Draghi, D. C., Pillar, C. M., Parr, T. R. Jr., Moeck, G., Sahm, D. F. (2009). Comparative In Vitro Activity Profile of Oritavancin against Recent Gram-Positive Clinical Isolates. Antimicrob. Agents Chemother. 53: 4762-4771 [Abstract] [Full Text]  


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