Combined Drug Treatment of Tuberculosis. I. Prevention of Emergence of Mutant Populations of Tubercle Bacilli Resistant to Both Streptomycin and Isoniazid in Vitro

Treatment of tuberculosis with single drug regimens employing streptomycin, para-aminosalicylic acid, or isoniazid has proved to be clinically inferior to the use of combinations of these drugs (1-3). The superiority of combined drug regimens has been manifest both in the percentage of patients rendered bacteriologically negative and in the lower incidence of the emergence of drug resistance. Ehrlich (4) first conceived the generalization that chemotherapy combining two or more effective agents with independent actions would prove superior to single drug treatment by tending to prevent the parasite from developing resistance to the action of either of the drugs. This principle