A comparison of various measures of sensitivity of M. tuberculosis to pyrazinamide.
Tripathy, S.P.; Mitchison, D.A.; Nair, N.G.K.; Radhakrishna, S.; Subbammal, S.
Indian Journal of Medical Research; 1971; 59; 175-189.
Information on the in vitro sensitivity of Mycobacterium tuberculosis to pyrazinamide is limited, mainly because of the difficulty in choosing an appropriate pH for the medium employed. A pyrazinamide sensitivity test, employing Lowenstein-Jensen medium acidified with hydrochloric acid to a preinspissation pH of 4.80-4.85, was developed at this Centre, and performed on cultures from tuberculous patients. Sensitivity was measured as the minimal inhibitory concentration (MIC) of pyrazinamide for various sizes of the inoculum, and as proportions of the bacterial population resistant to various concentrations of the drug. For each measure, the findings in patients with no history of previous chemotherapy with pyrazinamide were compared with those obtained at 4-12 months after the start of daily treatment with pyrazinamide; the definition of resistance was chosen such that it discriminated efficiently between the two populations, and classified only a small proportion of the former population as resistant. Four definitions of resistance were chosen - an MIC of 200 µg/ml or more employing an inoculum containing approximately 0.4 mg of bacilli per ml and a 10-colony end-point, and proportions 20% or more on 25 µg/ml, 5% or more on 50 µg/ml, and 1% or more on 100 µg/ml. The four definitions were of similar efficiency. Employing them, it was found that wild strains with consistent resistance to pyrazinamide were rare in Madras patients; also, in patients who received daily pyrazinamide, resistance emerged (if at all) at 4-6 months after the start of treatment.
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