Treatment-Shortening Effect of a Novel Regimen Combining Clofazimine and High-Dose Rifapentine in Pathologically Distinct Mouse Models of Tuberculosis.
Animals
Antibiotics, Antitubercular
/ administration & dosage
Antitubercular Agents
/ administration & dosage
Clofazimine
/ administration & dosage
Disease Models, Animal
Drug Administration Schedule
Drug Therapy, Combination
/ methods
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Rifampin
/ administration & dosage
Tuberculosis
/ drug therapy
BALB/c mice
C3HeB/FeJ mice
clofazimine
mouse models
rifapentine
tuberculosis
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
20
02
2019
accepted:
22
03
2019
pubmed:
3
4
2019
medline:
14
4
2020
entrez:
3
4
2019
Statut:
epublish
Résumé
Clofazimine and high-dose rifapentine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure. We tested this hypothesis in a well-established BALB/c mouse model of TB chemotherapy and also in a C3HeB/FeJ mouse model in which mice can develop caseous necrotic lesions, an environment where rifapentine and clofazimine may individually be less effective. In both mouse models, replacing rifampin with high-dose rifapentine and adding clofazimine in the first-line regimen resulted in greater bactericidal and sterilizing activity than either modification alone, suggesting that a rifapentine- and clofazimine-containing regimen may have the potential to significantly shorten the treatment duration for drug-susceptible TB. These data provide preclinical evidence supporting the evaluation of regimens combining high-dose rifapentine and clofazimine in clinical trials.
Identifiants
pubmed: 30936097
pii: AAC.00388-19
doi: 10.1128/AAC.00388-19
pmc: PMC6535519
pii:
doi:
Substances chimiques
Antibiotics, Antitubercular
0
Antitubercular Agents
0
Clofazimine
D959AE5USF
Rifampin
VJT6J7R4TR
rifapentine
XJM390A33U
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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