Abstract
A system is described for the study of the activity of drugs against tubercle bacilli growing in cells of human origin (HeLa cells). The effective drugs can be divided into 2 groups. In the first group were the drugs with full activity against bacilli already within the cells. Thus the same minimal inhibitory concentrations were observed with an "early" schedule of drug administration, in which the drug was present during the period of phagocytosis, as by a "delayed" schedule, in which the drug was withheld until the bacilli had entered the cell. In addition, the same minimal inhibitory concentration was found in the usual tests in bacteriological media. This group of drugs was made up of cycloserine, isonicotinic acid hydrazide (isoniazid), and pyrazinamide. In the 2d group were drugs exhibiting decreased activity against intracellular bacilli, so that higher minimal inhibitory concentrations were found by the "delayed" than by the "early" schedule in HeLa cells, and both of these values were higher than those found in the absence of cells in bacteriological media. Into this 2d group of drugs fell para-aminosalicylic acid, streptomycin, tetracyclin, and viomycin.