This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Heine, H. S.
Right arrow Articles by Moeck, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heine, H. S.
Right arrow Articles by Moeck, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2008, p. 3350-3357, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00360-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax {triangledown}

H. S. Heine,1* J. Bassett,1 L. Miller,1 A. Bassett,1 B. E. Ivins,1 D. Lehoux,2 F. F. Arhin,2 T. R. Parr Jr.,2 and G. Moeck2

United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Maryland,1 Targanta Therapeutics, St-Laurent, Quebec, Canada2

Received 14 March 2008/ Returned for modification 18 May 2008/ Accepted 23 June 2008

The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days. The potent in vitro activity of oritavancin, a semisynthetic lipoglycopeptide, against B. anthracis (MIC against Ames strain, 0.015 µg/ml) prompted us to test its efficacy in a mouse aerosol-anthrax model. In postexposure prophylaxis dose-ranging studies, a single intravenous (i.v.) dose of oritavancin of 5, 15, or 50 mg/kg 24 h after a challenge with 50 to 75 times the median lethal dose of Ames strain spores provided 40, 70, and 100% proportional survival, respectively, at 30 days postchallenge. Untreated animals died within 4 days of challenge, whereas 90% of control animals receiving ciprofloxacin at 30 mg/kg intraperitoneally twice daily for 14 days starting 24 h after challenge survived. Oritavancin demonstrated significant activity post symptom development; a single i.v. dose of 50 mg/kg administered 42 h after challenge provided 56% proportional survival at 30 days. In a preexposure prophylaxis study, a single i.v. oritavancin dose of 50 mg/kg administered 1, 7, 14, or 28 days before lethal challenge protected 90, 100, 100, and 20% of mice at 30 days; mice treated with ciprofloxacin 24 h or 24 and 12 h before challenge all died within 5 days. Efficacy in pre- and postexposure models of inhalation anthrax, together with a demonstrated low propensity to engender resistance, promotes further study of oritavancin pharmacokinetics and efficacy in nonhuman primate models.

* Corresponding author. Mailing address: Division of Bacteriology, USAMRIID, 1425 Porter St., Ft. Detrick, MD 21702-5011. Phone: (301) 619-4887. Fax: (301) 619-8351. E-mail: henry.heine{at}amedd.army.mil

{triangledown} Published ahead of print on 7 July 2008.

Antimicrobial Agents and Chemotherapy, September 2008, p. 3350-3357, Vol. 52, No. 9
0066-4804/08/$08.00+0     doi:10.1128/AAC.00360-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thomas, J. M., Moen, S. T., Gnade, B. T., Vargas-Inchaustegui, D. A., Foltz, S. M., Suarez, G., Heidner, H. W., Konig, R., Chopra, A. K., Peterson, J. W. (2009). Recombinant Sindbis Virus Vectors Designed To Express Protective Antigen of Bacillus anthracis Protect Animals from Anthrax and Display Synergy with Ciprofloxacin. CVI 16: 1696-1699 [Abstract] [Full Text]  
  • Sela-Abramovich, S., Chitlaru, T., Gat, O., Grosfeld, H., Cohen, O., Shafferman, A. (2009). Novel and Unique Diagnostic Biomarkers for Bacillus anthracis Infection. Appl. Environ. Microbiol. 75: 6157-6167 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»