Combined Drug Treatment

Microbiologic investigation of the prevention of emergence of mutant populations of tubercle bacilli resistant to streptomycin and isoniazid emphasized the fact that adequate concentrations of each of these two appropriate drugs were necessary (1). Delivery of such concentrations of isoniazid to the multiplying parasites can be estimated by microbiologic assay (2-4). Antimicrobially-active serum streptomycin assayed by a similar microbiologic method confirmed that there were also probably significant variations between individuals in serum levels of this drug as well. These observations suggested that conventional dosages of these drugs could not be relied upon to insure the delivery in vivo of sterilizing concentrations of each agent to physiologically-susceptible tubercle bacilli. The result of consideration of these principles was the formulation of a chemotherapeutic regimen combining high dosage of streptomycin with high dosage of isoniazid for all patients (5-7). The purpose of this report (the third of a series) is to present the results of clinical application of this approach to chemotherapy of pulmonary tuberculosis.