ACTIVITY OF PYRAZINAMIDE IN A MURINE MODEL AGAINST MYCOBACTERIUM-TUBERCULOSIS ISOLATES WITH VARIOUS LEVELS OF IN-VITRO SUSCEPTIBILITY

The activity of pyrazinamide (PZA) against eight isolates of Mycobacte rium tuberculosis in a murine infection model was evaluated. M. tuberc ulosis isolates with various degrees of in vitro susceptibility to PZA (MIG range, 32 to >2,048 mu g/ml) were used. Four-week-old female mic e were infected intravenously with approximately 10(7) viable M. tuber culosis organisms, PZA at 150 mg/kg of body weight was started 1 day p ostinfection and given 5 days/week for 4 weeks. Infected but untreated mice were compared,vith PZA-treated mice. Mice were sacrificed at the completion of the treatment period, and viable cell counts were deter mined from homogenates of spleens and right lungs, PZA had activity in the murine test system against M. tuberculosis isolates for which the MICs were less than or equal to 256 mu g/ml. However, there was an in consistent correlation between the absolute MICs and the reductions in organ viable cell counts, Studies with drug-resistant A(l. tuberculos is isolates with an isogenic background would improve evaluation of dr ug efficacy in the murine test system. Further evaluation of antimycob acterial agents against monodrug-resistant isolates will provide data that will be useful for development of algorithms for treatment of inf ection with drug-resistant organisms.