Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens.
The effectiveness of various once-weekly 10 mg/kg rifapentine (P)- containing regimens for treatment of tuberculosis was assessed in mice infected intravenously with 4.3 x 10(6) colony-forming units (cfu) of Mycobacterium tuberculosis H37Rv, and treated 14 d later with various combinations of rifampin (R), P, isoniazid (H), pyrazinamide (Z), ethambutol (E), or streptomycin (S). Control mice treated daily with either 2-mo HRZ + 4-mo HR or 2-mo HRZ + 6-mo HE were rendered spleen and lung culture-negative at 6 mo and 8 mo, respectively. Treatment failure with emergence of R-resistant bacilli occurred in all mice given once-weekly monotherapy with P for 6 mo. Once-weekly PH treatment was successful at 6 mo when it was preceded by a 2-mo daily phase with HRZ. When the initial daily phase was reduced to 2 wk, once-weekly PH-containing treatment was successful, at 6 mo, only if it was supplemented with S during the initial daily and the once-weekly phases, and at 8 mo if it was supplemented with daily H during the once-weekly phase. Without these supplements, once-weekly treatment failed in some mice with selection of R-resistant or H-resistant mutants.
Daniel
N
N
Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Lounis
N
N
Ji
B
B
O'Brien
R J
RJ
Vernon
A
A
Geiter
L J
LJ
Szpytma
M
M
Truffot-Pernot
C
C
Hejblum
G
G
Grosset
J
J
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage*; D000995:Antitubercular Agents / Q000008:administration & dosage; D015169:Colony Count, Microbial; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage; D005260:Female; D007538:Isoniazid / Q000008:administration & dosage; D008168:Lung / Q000382:microbiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D011718:Pyrazinamide / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013154:Spleen / Q000382:microbiology; D013307:Streptomycin / Q000008:administration & dosage; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine; D013307:Streptomycin