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Antimicrobial Agents and Chemotherapy, April 2007, p. 1150-1154, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00620-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Bactericidal Activity and Resistance Development Profiling of Dalbavancin{triangledown}

Beth P. Goldstein,3 Deborah C. Draghi,1 Daniel J. Sheehan,2 Patricia Hogan,2 and Daniel F. Sahm1*

Focus Bio-Inova, Inc., Herndon, Virginia,1 Pfizer Inc., Pfizer Global Pharmaceuticals, New York, New York,2 Pfizer Inc., Pfizer Global Pharmaceuticals, King of Prussia, Pennsylvania3

Received 19 May 2006/ Returned for modification 14 July 2006/ Accepted 21 December 2006

Dalbavancin, a semisynthetic lipoglycopeptide being developed for the treatment of skin and skin structure infections (SSSIs), has a half-life of 5 to 7 days in humans and offers promise for a convenient weekly dosing regimen. We studied the in vitro bactericidal activity of dalbavancin against target organisms, using the concentrations that are maintained in human blood with the proposed dosage regimen. Dalbavancin minimal bactericidal concentrations (MBCs) were ≤0.5 µg/ml for eight staphylococcal isolates; and for six of these strains, including one vancomycin-intermediate Staphylococcus aureus (VISA) isolate, the MBCs were equal to or within 1 doubling dilution of the MIC. Dalbavancin MICs for all three Streptococcus pyogenes strains were 0.008 µg/ml, as were the MBCs for two of the isolates. In time-kill studies conducted with a different set of seven strains (two methicillin-susceptible S. aureus isolates, three methicillin-resistant S. aureus isolates, one VISA isolate, and one S. pyogenes isolate), all strains exhibited a ≥3-log10 decrease in their viable counts when they were exposed to ≥1 µg/ml of dalbavancin for 24 h. Resistance development studies by both direct selection (resistance frequency, <10–10) and serial passage failed to produce stable mutants with decreased susceptibility to dalbavancin. These observations suggest that dalbavancin will be an effective choice for the management of patients with SSSIs.

* Corresponding author. Mailing address: Focus Bio-Inova, Inc., 13665 Dulles Technology Drive, Suite 200, Herndon, VA 20171-4603. Phone: (703) 480-2536. Fax: (703) 480-2654. E-mail: dsahm{at}focusbioinova.com

{triangledown} Published ahead of print on 12 January 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1150-1154, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.00620-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • McKay, G. A., Beaulieu, S., Arhin, F. F., Belley, A., Sarmiento, I., Parr, T. Jr, Moeck, G. (2009). Time-kill kinetics of oritavancin and comparator agents against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium. J Antimicrob Chemother 63: 1191-1199 [Abstract] [Full Text]  
  • Dowell, J. A., Goldstein, B. P., Buckwalter, M., Stogniew, M., Damle, B. (2008). Pharmacokinetic-Pharmacodynamic Modeling of Dalbavancin, a Novel Glycopeptide Antibiotic. J Clin Pharmacol 48: 1063-1068 [Abstract] [Full Text]  


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