Klemens S P, Grossi M A, Cynamon M H
SUNY Health Science Center, Syracuse 13210.
Antimicrob Agents Chemother. 1994 Oct;38(10):2245-8. doi: 10.1128/AAC.38.10.2245.
The activity of KRM-1648 was evaluated in a murine model of tuberculosis. Approximately 10(7) viable Mycobacterium tuberculosis ATCC 35801 organisms were given intravenously to 4-week-old female outbred mice. Treatment was started 1 week postinfection and given by gavage for 4 weeks. Viable-cell counts were determined from homogenates of spleen and lung tissues. The activity of KRM-1648 was compared with those of rifampin and rifabutin at 20 mg/kg of body weight. KRM-1648 was more active than either rifampin or rifabutin against organisms in spleens and lungs. KRM-1648 alone and in combination with either isoniazid, ethambutol, pyrazinamide, or levofloxacin was evaluated. Other treatment groups received isoniazid, ethambutol, pyrazinamide, or levofloxacin as single agents. KRM-1648 was the most active single agent evaluated. KRM-1648-pyrazinamide and KRM-1648-isoniazid were the most active combinations. These combinations were more active than KRM-1648 alone. The promising activity of KRM-1648 in M. tuberculosis-infected mice suggests that it is a good candidate for clinical development as a new antituberculosis agent.
在结核病小鼠模型中评估了KRM-1648的活性。将约10⁷个活的结核分枝杆菌ATCC 35801菌株静脉注射给4周龄的雌性远交系小鼠。感染后1周开始治疗，通过灌胃给药4周。从脾脏和肺组织匀浆中测定活菌数。将KRM-1648的活性与体重20mg/kg的利福平及利福布汀的活性进行比较。KRM-1648对脾脏和肺中的细菌的活性比利福平或利福布汀更强。评估了单独使用KRM-1648以及KRM-1648与异烟肼、乙胺丁醇、吡嗪酰胺或左氧氟沙星联合使用的情况。其他治疗组分别接受异烟肼、乙胺丁醇、吡嗪酰胺或左氧氟沙星作为单一药物治疗。KRM-1648是所评估的最具活性的单一药物。KRM-1648-吡嗪酰胺和KRM-1648-异烟肼是最具活性的组合。这些组合比单独使用KRM-1648更具活性。KRM-1648在结核分枝杆菌感染小鼠中显示出的有前景的活性表明，它作为一种新型抗结核药物是临床开发的良好候选药物。
