Elsevier

Research in Microbiology

Volume 140, Issue 4, May–June 1989, Pages 301-309
Research in Microbiology

Rapid radiometric method for pyrazinamide susceptibility testing of Mycobacterium tuberculosis

Presented 26 October, 1988 at 28th Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles, California (USA)
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Abstract

Pyrazinamide (PZA) is one of the most important drugs in modern chemotherapy of tuberculosis. Since PZA is active only at an acid pH, testing the susceptibility of Mycobacterium tuberculosis to PZA is difficult and time-consuming. Therefore, we evaluated the BACTEC system for rapid testing of PZA susceptibility at pH 6. A total of 91 M. tuberculosis strains and 2 different strains of M. bovis BCG were screened for susceptibility to PZA. Each strain was tested in special 7H12 brth supplemented with polyoxyethylene stearate cotaining 25, 50 and 100 μg PZA/ml. Strains resistant to 100 μg/ml were retested against 25–100 μg/ml and at an extended range of PZA concentrations from 200-6, 400 μg/ml. The MIC was determined with all strains within 4–20 (mean 7) days. Of the 77 susceptible strains, based on the pyrazinamidase test, MIC were ⩽ 25 μg/ml for 34 strains, 50 for 38 and 100 for 2 strains. Three pyrazinamidase-positive strains had still higher MIC, 1 at 800 and 2 at 3,200 μg/ml. PZA-resistant strains had MIC of 800 or greater. Monoresistance to PZA has not been detected to date. The clear bimodal distribution of MIC in this method could enable the routine clinical microbiology laboratory to perform PZA susceptibility testing as easily as the 4 drugs now tested in the BACTEC system.

Keywords

Mycobacterium tuberculosis
Pyrazinamide
pH
Susceptibility testing
BACTEC system

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