Comparison of techniques for measuring the isoniazid resistance of tubercle bacilli.

As with streptomycin and P.A.S., the introduction of isoniazid for the treatment of tuberculosis has raised the problem of the development of resistance to the drug in strains of tubercle bacilli recovered from treated patients. In the Medical Research Council (1952) trials 71% of cultures from patients who had received three months' treatment with isoniazid alone were found to be resistant. Although combined treatment with isoniazid and streptomycin may markedly reduce this high incidence of resistant strains, it will still be essential to measure the sensitivity of tubercle bacilli recovered from patients before, during, and after treatment. A number of methods have been used for determining the sensitivity of tubercle bacilli to streptomycin and other chemotherapeutic agents. These can be classified as (1) the direct test, when the sputum concentrate is placed directly on to a series of solid medium slopes containing a range of drug concentrations; (2) the indirect test, when a suspension of a primary culture on drug-free medium is inoculated on to a similar series of solid or fluid media containing a range of drug concentrations; and (3) the subculture test, when the strain is subcultured into liquid medium, usually Dubos Tween-albuimin medium, and then the resulting growth is inoculated into tubes of the same medium containing a range of drug concentrations. This last method has been recommended by the Medical Research Council (1948) for streptomycin, since the test can be performed under standardized conditions in a medium with a constant pH and composition. During the Medical Research Council trials of isoniazid a series of experiments was carried out to investigate the behaviour of isoniazid-resistant strains in the indirect and subculture tests, since these were thought to be the methods most likely to be adopted in practice.