title: Activity of KRM-1648 alone or in combination with both ethambutol and kanamycin or clarithromycin against Mycobacterium intracellulare infections in beige mice.
abstract: 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.
authors.affiliation: Department of Infection and Inflammation, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: R
authors.initials: R
authors.lastname: Amitani
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Murayama
authors.forename: F
authors.initials: F
authors.lastname: Kuze
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D007612:Kanamycin / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D012293:Rifampin / Q000627:therapeutic use; D012294:Rifamycins / Q000008:administration & dosage / Q000627:therapeutic use*; D013154:Spleen / Q000382:microbiology; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D012294:Rifamycins; C068980:KRM 1648; D007612:Kanamycin; D004977:Ethambutol; D017291:Clarithromycin; D012293:Rifampin