THE EARLY BACTERICIDAL ACTIVITY OF DRUGS IN PATIENTS WITH PULMONARY TUBERCULOSIS

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Abstract
Counts of colony-forming units of Mycobacterium tuberculosis in sputum were done on selective medium during the first 2 wk of treatment of 124 patients with pulmonary tuberculosis. The 27 chemotherapy regimens studied included daily administration of thiacetazone, p-aminosalicylic acid, pyrazinamide, rifampin, streptomycin, ethambutol and isoniazid alone and certain 2 drug, 3 drug and 4 drug combinations. Thiacetazone and p-aminosalicylic acid appeared to be only bacteriostatic. The mean fall in counts and the differences between regimens containing the remaining bactericidal drugs were greater during the 1st 2 days of treatment than during the remaining 12 days. The early (0-2 day) falls were much larger with isoniazid than with other drugs. Rifampin was less bactericidal, and may have reduced the bactericidal activity of the 3 drug and 4 drug combinations, including isoniazid. Although streptomycin and pyrazinamide were only slightly bactericidal alone or in a 2 drug combination, the 3 drug regimen of isoniazid, streptomycin and pyrazinamide produced the largest early fall in counts encountered. The occurrence of definite though slight bactericidal activity of pyrazinamide alone throughout the 14 day period raised the question of how pyrazinamide acts in vivo; the finding may imply that bacilli in cavity walls are often in a very acid environment. The striking disagreement between the ranking of drugs and drug combinations in their ability to cause an early fall in counts and their ultimate sterilizing ability suggested that the mechanisms operative in sterilizing lesions, probably involving the killing of special portions of the residual bacterial population, are different from those responsible for early bactericidal action in vivo or in vitro.