Skip Navigation


JAC Advance Access originally published online on August 29, 2007
Journal of Antimicrobial Chemotherapy 2007 60(5):994-998; doi:10.1093/jac/dkm291
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
60/5/994    most recent
dkm291v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Saliu, O. Y.
Right arrow Articles by Wallis, R. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saliu, O. Y.
Right arrow Articles by Wallis, R. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Bactericidal activity of OPC-67683 against drug-tolerant Mycobacterium tuberculosis

Oluwabunmi Y. Saliu1, Catina Crismale1, Stephan K. Schwander1 and Robert S. Wallis1,2,*

1 UMDNJ-New Jersey Medical School, 185 S. Orange Avenue, MSB-185, Newark, NJ, USA 2 PPD, 1213 N St. NW, Suite A, WA DC 20005, USA

Received 7 April 2007; returned 19 June 2007; revised 1 July 2007; accepted 11 July 2007

* Corresponding author. Tel: +1-202-360-4784; Fax: +1-919-654-0640; E-mail: robert.wallis{at}columbia.ppdi.com

Objectives: There is an urgent need for drugs that hasten sterilization in tuberculosis; however, we presently lack indicators of this activity to guide early drug development. We previously described a novel in vitro assay to study mycobacterial phenotypic drug tolerance, in which sterilizing activity could be assessed. OPC-67683 is a novel imidazooxazole that accelerates sterilization in the mouse tuberculosis model. The present study was conducted to determine the activity of OPC-67683 in the in vitro tolerance model using drug-tolerant clinical Mycobacterium tuberculosis strains.

Methods: Tolerance was assessed in Bactec radiometric culture as: (i) delayed decline in growth index during 14 days of drug exposure; (ii) shorter time to positivity of subcultures following drug exposure.

Results: Four isolates were selected from among 16 surveyed, based on delayed killing by isoniazid and OPC-67683. Unlike isoniazid and rifampicin, whose rates of killing were concentration-independent, OPC-67683 showed concentration-dependent effects that, at the highest dose levels tested (1.0 µg/mL), were superior to isoniazid and equal to rifampicin.

Conclusions: The sterilizing activity of OPC-67683 against drug-tolerant M. tuberculosis in the Bactec model is consistent with its activity in mice. Further studies are warranted to examine the effects of OPC-67683 on mycobacterial persistence in tuberculous patients and to determine the biological basis of tolerance in the model.

Keywords: tuberculosis , relapse , sterilization , tolerance


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.