ACTIVITY OF KRM-1648, A NEW BENZOXAZINORIFAMYCIN, AGAINST MYCOBACTERIUM-TUBERCULOSIS IN A MURINE MODEL

The activity of KRM-1648 was evaluated in a murine model of tuberculos is. Approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 o rganisms were given intravenously to 4-week-old female outbred mice. T reatment was started 1 week postinfection and given by gavage for 4 we eks. Viable-cell counts were determined from homogenates of spleen and lung tissues. The activity of KRM-1648 was compared,vith those of rif ampin and rifabutin at 20 mg/kg of body weight. KRM-1648 was more acti ve than either rifampin or rifabutin against organisms in spleens and lungs. KRM-1648 alone and in combination,vith either isoniazid, ethamb utol, pyrazinamide, or levofloxacin,vas evaluated. Other treatment gro ups received isoniazid, ethambutol, pyrazinamide, or levofloxacin as s ingle agents. KRM-1648 was the most active single agent evaluated. KRM -1648-pyrazinamide and KRM-1648-isoniazid were the most active combina tions. These combinations were more active than KRM-1648 alone. The pr omising activity of KRM-1648 in M. tuberculosis-infected mice suggests that it is a good candidate for clinical development as a new antitub erculosis agent.