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.

Tubercle; 1970; 51; 375-388.

A test, employing Lowenstein-Jensen medium acidified with hydrochloric acid to a preinspissation pH of 4.80-4.85, is described for detecting the sensitivity to pyrazinamide of strains of M. tuberculosis . The test was performed on cultures from patients with no history of previous chemotherapy with pyrazinamide, and on cultures from patients receiving daily treatment with pyrazinamide.

          Sensitivity was measured in terms of the minimal inhibitory concentration of the drug for various sizes of the inoculum, and as proportions of the bacterial population resistant to various concentrations of the drug. For each of these measures, 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 then chosen such that (a) it discriminated efficiently between the two populations, and (b) it classified only a small proportion of the former population as resistant.

          Four definitions of resistance were chosen - a minimal inhibitory concentration of 200 µg/ml. or more employing an inoculum containing approximately 0.4 mg. (moist weight) of bacilli per ml. and a 10-colony end-point, and proportions of 20% or more on 25µg/ml., 5% or more on 50µg/ml., and 1% or more on 100µg/ml. The efficiency of the four definitions was of the same order. Further, highly satisfactory agreement was obtained between pairs of definitions in the classification of individual cultures as sensitive or resistant.

          High viable counts on the drug-free acidified medium were associated with high minimal inhibitory concentrations but had little effect on the proportions resistant.

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