Therapeutic effect of KRM-1648 with various antimicrobials against Mycobacterium avium complex infection in mice.
A new benzoxazinorifamycin, KRM-1648 (KRM), was studied for its therapeutic efficacy in combination with other antimicrobials against Mycobacterium avium complex infections in mice. When M. intracellulare-infected (intravenously) mice were given KRM, clarithromycin (CAM), sparfloxacin (SPFX), or ethambutol (EB) each alone or in combination, by gavage, once daily 6 times per week (streptomycin [SM] was given subcutaneously twice per week) from day 1, KRM + CAM exhibited combined efficacy in terms of reducing the incidence of gross lung lesions and the bacterial loads in the lungs and spleens. The addition of either EB or EB + SPFX to KRM + CAM increased the efficacy. Moreover, the multi-drug regimen of KRM + CAM + EB + SPFX or ofloxacin [OFLX]) was more efficacious than rifampicin (RMP) + CAM + EB + SPFX (or OFLX). In M. avium infection, KRM + clofazimine was the most efficacious among two-drug combinations tested followed by KRM + SM. KRM + CAM was considerably less effective against M. avium than against M. intracellulare infection. KRM + EB and KRM+OFLX failed to show such a combined effect.
Saito
H
H
Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
Tomioka
H
H
Sato
K
K
Kawahara
S
S
Hidaka
T
T
Dekio
S
S
D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use; D002991:Clofazimine / Q000627:therapeutic use; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004977:Ethambutol / Q000627:therapeutic use; D024841:Fluoroquinolones; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D015242:Ofloxacin / Q000627:therapeutic use; D015363:Quinolones / Q000627:therapeutic use; D012294:Rifamycins / Q000627:therapeutic use*; D013307:Streptomycin / Q000627:therapeutic use
D000995:Antitubercular Agents; D024841:Fluoroquinolones; D015363:Quinolones; D012294:Rifamycins; C068980:KRM 1648; D004977:Ethambutol; D015242:Ofloxacin; D002991:Clofazimine; D017291:Clarithromycin; C061363:sparfloxacin; D013307:Streptomycin