Prevention of drug carryover effects in studies assessing antimycobacterial efficacy of TMC207.

ABSTRACT

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 microg/ml), 7H11 agar supplemented with 5% bovine serum albumin (BSA; MIC = 1 microg/ml), and Lowenstein-Jensen medium (MIC = 14.33 microg/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 microg/ml for 7H11 agar, 32.33 microg/ml for 7H11 agar with 5% BSA, and 96.33 microg/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.