Evaluation of moxifloxacin-containing regimens in pathologically distinct murine tuberculosis models.
Antimicrob Agents Chemother
; 59(7): 4026-30, 2015 Jul.
Article
en En
| MEDLINE
| ID: mdl-25918146
ABSTRACT
In the recently concluded REMox-TB trial, two 4-month moxifloxacin-containing regimens did not meet the criteria for noninferiority compared to the current 6-month first-line regimen to treat tuberculosis (TB). Despite the disappointing result, this phase 3 clinical trial provides a rare opportunity to gauge the predictive accuracy of the nonclinical models used to support regimen development. In parallel with the REMox-TB trial, we compared the efficacy of the same three regimens against chronic TB infection in the commonly used BALB/c mouse strain and in C3HeB/FeJ mice, which have attracted recent interest as a nonclinical efficacy model because they develop caseous lung lesions which may better resemble human TB. In long-term treatment experiments at two institutions, using low-dose aerosol infection models with 6- to 8-week incubation periods in both mouse strains, control mice received rifampin, isoniazid, pyrazinamide, and ethambutol (RHZE), and test mice received the same regimen with moxifloxacin replacing isoniazid (RMZE) or ethambutol (RHZM). Outcome measures were lung CFU counts during treatment and relapse after various durations of treatment. At both institutions and in both mouse strains, RMZE and RHZM reduced by approximately 1 month and 0 to 1 month, respectively, the treatment duration needed to produce the same relapse rate as RHZE. These results demonstrating generally similar treatment-shortening effects of the moxifloxacin-containing regimens in each mouse strain, with effect sizes consistent with the REMox-TB trial results, reinforce the predictive value of murine models for TB regimen development.
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Terapias_biologicas
/
Aromoterapia
Asunto principal:
Tuberculosis Pulmonar
/
Fluoroquinolonas
/
Antibacterianos
/
Antituberculosos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos