Activity of KRM-1648 alone or in combination with both ethambutol and kanamycin or clarithromycin against Mycobacterium intracellulare infections in beige mice.

The in vivo activities of KRM-1648 alone or in combination with both ethambutol (EB) and kanamycin (KM) or clarithromycin (CAM) were tested against Mycobacterium intracellulare infections in beige mice. KRM-1648 was more active than rifampin (RFP) when each drug was used alone, and the efficacy of KRM-1648 was similar to those of both kanamycin and clarithromycin. The combination KRM-1648-KM-EB was strongly active and rapidly reduced the numbers of bacilli both in lungs and in spleens compared with RFP-KM-EB. The combination KRM-1648-CAM had greater therapeutic effects than RFP-CAM; this difference in efficacy was more pronounced for lungs than for spleens. These findings suggest that KRM-1648 is a promising candidate for combination therapy with other potent antimycobacterial drugs.