M. TUBERCULOSIS IN VITRO SUSCEPTIBILITY AND SERUM LEVEL EXPERIENCES WITH CAPREOMYCIN

The material to be presented represents results accumulated in our laboratory in support of clinical trials with the new antibiotic capreomycin. These data include results of in vitro studies on the minimal inhibitory concentration (MIC) of capreomycin against Mycobacterium tuberculosis, strain H37Rv, as compared to the MIC of other antituberculosis drugs against this organism. Also included are cross-resistance studies against drug-resistant and drugsusceptible strains of M. tuberculosis recovered from tuberculous patients. In addition, the data presents results of studies designed to evaluate possible cross-resistance to capreomycin of drug-resistant mutants of M . tuberculosis, strain H37Rv, sequentially selected resistant to isoniazid, streptomycin, or p-amino salicylic acid alone, or to mutants resistant to any two or all three of these drugs. In three instances, mutants were selected resistant to ethionamide, in addition to combinations of isoniazid, streptomycin and p-amino salicylic acid. Finally, data will be presented to demonstrate serum concentrations of capreomycin determined by biologic assay procedure on blood drawn from subjects and patients who had received this drug by intramuscular injection . The basal medium used in these studies was Middlebrook's 7H10 oleic acid-albumin liquid medium (7H10 OA). Agar was added for direct and indirect plating experiments. Tween 80 was added for preparation of smooth standardized inocula but was not added to the liquid medium used for capreomycin serum biologic assays. 1