Combination of rifapentine-moxifloxacin-minocycline (PMM) for the treatment of leprosy.
To further the development of a multidrug regimen for treatment of leprosy that is suitable for monthly administration and fully supervisable, the bactericidal activities against Mycobacterium leprae of HMR 3647 (HMR), moxifloxacin (MXFX) and rifapentine (RPT) were measured by the proportional bactericide technique in the mouse footpad system, and compared with those of the established antileprosy drugs clarithromycin (CLARI), ofloxacin (OFLO) and rifampicin (RMP). Administered in five daily doses of 100 mg per kg body weight, HMR appeared slightly more bactericidal than CLARI, but the difference did not attain statistical significance. Administered as single doses, MXFX in a dosage of 150 mg per kg was more active than OFLO in the same dosage, and displayed the same level of activity as RMP in a dosage of 10 mg per kg; the combination MXFX-minocycline (MINO) (MM) was more bactericidal than the combination OFLO-MINO (OM); RPT in a dosage of 10 mg per kg was more bactericidal than RMP administered in the same dosage, and even more active than the combination RMP-OFLO-MINO (ROM); the combination RPT-MXFX-MINO (PMM) killed 99.9% of viable M. leprae, and was slightly more bactericidal than was RPT alone, indicating that the combination PMM showed an additive effect against M. leprae. These promising results justify a clinical trial among lepromatous patients, in which MM is being compared with OM, and PMM with ROM, in terms of efficacy and tolerance.
Ji
B
B
Faculté de Médicine Pitié-Salpêtrière, Paris, France.
Grosset
J
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001372:Aza Compounds; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones; D007917:Leprostatic Agents / Q000008:administration & dosage*; D007918:Leprosy / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D008911:Minocycline / Q000008:administration & dosage*; D000077266:Moxifloxacin; D011336:Probability; D011804:Quinolines; D012293:Rifampin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D007917:Leprostatic Agents; D011804:Quinolines; D008911:Minocycline; D000077266:Moxifloxacin; D012293:Rifampin; C018421:rifapentine