Efficient intermittent rifapentine-moxifloxacin-containing short-course regimen for treatment of tuberculosis in mice.
Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 x10(6) CFU of Mycobacterium tuberculosis H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.
Veziris
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Laboratoire de Bactériologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France. veziris@chups.jussieu.fr
Lounis
N
N
Chauffour
A
A
Truffot-Pernot
C
C
Jarlier
V
V
D000818:Animals; D021461:Animals, Outbred Strains; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones; D051379:Mice; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis; D011804:Quinolines / Q000008:administration & dosage*; D011897:Random Allocation; D012293:Rifampin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015996:Survival Rate; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin; D012293:Rifampin; C018421:rifapentine