JAC Advance Access published online on April 15, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp126
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original research |
Time–kill kinetics of oritavancin and comparator agents against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium
Targanta Therapeutics Inc., 7170 Frederick Banting, St Laurent, QC, Canada H4S 2A1
Received 22 December 2008; returned 26 February 2009; revised 12 March 2009; accepted 12 March 2009
* Corresponding author. Tel: +1-514-332-1008 ext. 232; Fax: +1-514-332-6033; E-mail: gmoeck{at}targanta.com
Objectives: Oritavancin, a lipoglycopeptide, possesses bactericidal activity against Gram-positive bacteria including vancomycin-resistant Staphylococcus aureus and enterococci. To understand the time dependence of oritavancin activity, we have undertaken time–kill experiments against isolates of S. aureus, Enterococcus faecalis and Enterococcus faecium, including recent antibiotic-resistant strains.
Methods: Six strains of S. aureus [methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA)] and five strains of enterococci [vancomycin-susceptible enterococci (VSE) and vancomycin-resistant enterococci (VRE; both VanA and VanB)] were tested in time–kill assays; oritavancin assays included 0.002% polysorbate-80 to ensure quantitative drug recovery. Oritavancin and comparators vancomycin, teicoplanin, linezolid and daptomycin were tested at static concentrations approximating their free peak (fCmax) and free trough (fCmin) in plasma when administered at standard doses for complicated skin and skin structure infections.
Results: Oritavancin showed concentration-dependent killing of all strains tested: at its fCmax predicted from a 200 mg dose in humans, oritavancin exerted bactericidal activity (
3 log kill relative to starting inoculum) against MSSA, MRSA and VRSA within 1 h and against VSE between 11 and 24 h. At predicted fCmax from an 800 mg dose, oritavancin was bactericidal against VISA strains at 24 h and against VRE at 10 h.
Conclusions: Oritavancin displayed concentration-dependent killing of MSSA, MRSA, VRSA, VISA, VSE and VRE. Oritavancin was more rapidly bactericidal against all strains tested than were vancomycin, teicoplanin, linezolid or daptomycin at physiologically relevant concentrations. These data support the conclusion that oritavancin exerts concentration-dependent bactericidal activity on recent, drug-resistant isolates of S. aureus and enterococci.
Key Words: lipoglycopeptide , bactericidal , resistance
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. F. Arhin, D. C. Draghi, C. M. Pillar, T. R. Parr Jr., G. Moeck, and D. F. Sahm Comparative In Vitro Activity Profile of Oritavancin against Recent Gram-Positive Clinical Isolates Antimicrob. Agents Chemother., November 1, 2009; 53(11): 4762 - 4771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. F. Arhin, I. Sarmiento, T. R. Parr Jr, and G. Moeck Comparative in vitro activity of oritavancin against Staphylococcus aureus strains that are resistant, intermediate or heteroresistant to vancomycin J. Antimicrob. Chemother., October 1, 2009; 64(4): 868 - 870. [Full Text] [PDF]
|
|