Determination of pyrazinamide MICs for Mycobacterium tuberculosis at different pHs by the radiometric method

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Abstract
The MICs of pyrazinamide (PZA) were determined for Mycobacterium tuberculosis cultivated under different pH conditions in 7H12 liquid medium. Mycobacterial growth was monitored by the radiometric method (BACTEC system; Johnston Laboratories, Inc., Towson, Md.). We observed a predictable eightfold difference between the MICs determined at pH 5.5 and those determined at pH 5.95. The highest MICs for 21 susceptible strains were 50.0 .mu.g/ml at pH 5.5 and 400 .mu.g/ml at pH 5.95. This eightfold difference enabled us to predict MICs at pH 5.5 from the values observed at pH 5.95. The use of 7H12 broth at pH 5.95 simplified the radiometric PZA susceptibility test by avoiding the addition of acid solutions in the course of cultivation, which was required when the test was performed at pH 5.5. An additional benefit of using pH 5.95 instead of pH 5.5 was that all tested strains grew at pH 5.95, while some of them, especially PZA-resistant strains, did not grow at pH 5.5.