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Journal of Clinical Microbiology, July 2008, p. 2212-2215, Vol. 46, No. 7
0095-1137/08/$08.00+0     doi:10.1128/JCM.00177-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Prevention of Drug Carryover Effects in Studies Assessing Antimycobacterial Efficacy of TMC207{triangledown}

Nacer Lounis,1* Tom Gevers,1 Joke Van Den Berg,1 Tom Verhaeghe,2 Rolf van Heeswijk,1 and Koen Andries1

Tibotec BVBA, Johnson & Johnson, Turnhoutseweg 30, Beerse 2340, Belgium,1 Pharmaceutical Research and Development, Johnson & Johnson, Turnhoutseweg 30, Beerse 2340, Belgium2

Received 29 January 2008/ Returned for modification 23 March 2008/ Accepted 3 May 2008

The levels of TMC207 (R207910) that can be reached in mouse organs and the sputa of treated patients easily exceed the MIC of the compound and can therefore interfere with in vitro bacterial titrations. We studied the usefulness of protein-enriched media for the prevention of such drug carryover effects. The average MIC of Mycobacterium tuberculosis was determined on three different media: unsupplemented 7H11 agar (MIC = 0.03 µg/ml), 7H11 agar supplemented with 5% bovine serum albumin (BSA; MIC = 1 µg/ml), and Lowenstein-Jensen medium (MIC = 14.33 µg/ml). In a second stage of the study, the maximal noninhibitory concentrations (MNICs) of TMC207 were determined by adding TMC207 to the bacterial inoculum rather than to the culture medium. These MNICs were 0.97 µg/ml for 7H11 agar, 32.33 µg/ml for 7H11 agar with 5% BSA, and 96.33 µg/ml for Lowenstein-Jensen medium. Both protein-enriched media were able to prevent drug carryover effects, but the use of 7H11 medium supplemented with 5% BSA is preferred for practical reasons.

* Corresponding author. Mailing address: BVBA, Johnson & Johnson, Turnhoutseweg 30, Beerse 2340, Belgium. Phone: 32 14 60 65 71. Fax: 32 14 60 54 03. E-mail: nlounis{at}tibbe.jnj.com

{triangledown} Published ahead of print on 14 May 2008.

Journal of Clinical Microbiology, July 2008, p. 2212-2215, Vol. 46, No. 7
0095-1137/08/$08.00+0     doi:10.1128/JCM.00177-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Diacon, A. H., Pym, A., Grobusch, M., Patientia, R., Rustomjee, R., Page-Shipp, L., Pistorius, C., Krause, R., Bogoshi, M., Churchyard, G., Venter, A., Allen, J., Palomino, J. C., De Marez, T., van Heeswijk, R. P.G., Lounis, N., Meyvisch, P., Verbeeck, J., Parys, W., de Beule, K., Andries, K., Neeley, D. F. M. (2009). The Diarylquinoline TMC207 for Multidrug-Resistant Tuberculosis. NEJM 360: 2397-2405 [Abstract] [Full Text]  


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