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J. Clin. Microbiol. doi:10.1128/JCM.00177-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Prevention of Drug Carry-Over Effects in Studies Assessing the Antimycobacterial Efficacy of TMC207

Tibotec Pharmaceuticals Ltd., Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium; and Pharmaceutical Research and Development, Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium

^* To whom correspondence should be addressed. Email: nlounis{at}tibbe.jnj.com.

	Abstract

The levels of TMC207 (R207910) that can be reached in mouse organs and sputa of treated patients easily exceed the MIC of the compound, and can therefore interfere with in vitro bacterial titrations. We studied the usefullness of protein-enriched media to prevent such drug carry-over effects. The average MIC of Mycobacterium tuberculosis was determined on 3 different media: unsupplemented 7H11 agar (MIC = 0.03 microgram/ml), 7H11 agar supplemented with 5% BSA (MIC = 1 microgram/ml) and Lowenstein Jensen (MIC = 14.33 microgram/ml). In a second stage, the maximal non inhibitory concentrations (MNIC) of TMC207 were determined by adding TMC207 to the bacterial inoculum rather than to the culture medium. These MNIC values 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 carry-over effects, but the use of 7H11 medium supplemented with 5% BSA is preferred for practical reasons.