Once-weekly rifapentine-containing regimens for treatment of tuberculosis in mice.
The bactericidal activities of several once-weekly rifapentine (P)-containing combination regimens against Mycobacterium tuberculosis, and their ability to prevent the selection of rifampin (R)-resistant mutants, were compared with those of the standard six-times-weekly regimen consisting of R, isoniazid (H), and pyrazinamide (Z) in a mouse experiment. Mice were infected intravenously with 1.3 x 10(7) cfu of M. tuberculosis strain H37Rv, and 8 wk of treatment began on Day 14 after infection, when mice were randomly allocated to an untreated control group and nine treatment groups of 30 mice each. At the end of 8 wk of treatment, all the tested regimens showed promising bactericidal activities. Once-weekly P alone was less bactericidal than six-times-weekly R alone; likewise, the once-weekly P-containing combined regimens were less bactericidal than the six-times-weekly standard regimen. However, the difference in killing was about 1 log10, which represented only a fraction of the overall 4 log10 to 5 log10 magnitude of killing effects. The addition of streptomycin (S) improved the bactericidal effect of once-weekly PHZ, and the effect of once-weekly PHZS was further enhanced when it was preceded by 2 wk of daily HZS. The latter regimen achieved the same level of activity as the standard six-times-weekly regimen. All of the once-weekly P-containing combined regimens were able to prevent the selection of R-resistant mutants, whereas monotherapy with R or P selected resistant mutants in approximately 50% of animals.
Grosset
J
J
Bactériologie et Hygiène, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Lounis
N
N
Truffot-Pernot
C
C
O'Brien
R J
RJ
Raviglione
M C
MC
Ji
B
B
D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D008168:Lung / Q000382:microbiology; D051379:Mice; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification; D009929:Organ Size; D011815:R Factors; D012293:Rifampin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D013307:Streptomycin / Q000008:administration & dosage; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
D000995:Antitubercular Agents; D012293:Rifampin; C018421:rifapentine; D013307:Streptomycin