In vitro studies on the choice of drugs for intermittent chemotherapy of tuberculosis

Abstract

Summary An attempt was made to study the effect of exposing cultures of Myco. tuberculosis for short periods to drugs used in the treatment of tuberculosis. Six drugs were used, the concentration of each being approximately ten times that necessary to inhibit growth. The cultures were exposed to these drugs for periods varying from two to 168 hours. Estimates of the number of viable organisms in the cultures were made before their exposure and at intervals after removal of the drug by washing with drug-free medium on a membrane filter. The effect of exposure was estimated by noting the delay before the organisms again began to grow. Streptomycin was considered most suitable for intermittent chemotherapy since it had the greatest bactericidal activity and the delay before growth began after exposure to the drug for six-96 hours and its subsequent removal, was eight-16 days; growth of organisms between doses would thus not be expected. Isoniazid and ethionamide appeared slightly less suitable as they only began to be bactericidal if the exposure period was at least one day and there was no delay before growth after exposure periods of 12 hours or less. However, after exposure periods of 24 hours or more, the delay before growth was three-17 days. With cycloserine, the delay before growth was only about one day after exposure for 24 hours but during exposure for 96 hours, this drug was more bactericidal than either isoniazid or ethionamide, and the delay before growth was then four-eight days. Thiacetazone and thiocarlide (4-4′ diisoamyloxythiocarbanilide) did not appear suitable for intermittent use since they were not bactericidal and growth started immediately after exposure.