Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection.
Am J Respir Crit Care Med
; 184(6): 732-7, 2011 Sep 15.
Article
en En
| MEDLINE
| ID: mdl-21659613
ABSTRACT
RATIONALE Multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is an emerging global health threat. Proper management of close contacts of infectious patients is increasingly important. However, no evidence-based recommendations for treating latent TB infection (LTBI) after MDR/XDR-TB exposure (DR-LTBI) exist. An ultrashort regimen for LTBI caused by drug-susceptible strains (DS-LTBI) is also desirable. TMC207 has bactericidal and sterilizing activity in animal models of TB and improves the activity of current MDR-TB therapy in patients. OBJECTIVES:
The objective of this study was to determine whether TMC207 might enable short-course treatment of DR-LTBI and ultrashort treatment of DS-LTBI.METHODS:
Using an established experimental model of LTBI chemotherapy in which mice are aerosol-immunized with a recombinant bacillus Calmette-Guérin vaccine before low-dose aerosol infection with Mycobacterium tuberculosis, the efficacy of TMC207 alone and in combination with rifapentine was compared with currently recommended control regimens as well as once-weekly rifapentine + isoniazid and daily rifapentine ± isoniazid. MEASUREMENTS Outcomes included monthly lung colony-forming unit counts and relapse rates. MAINRESULTS:
Lung colony-forming unit counts were stable at about 3.75 log(10) for up to 7.5 months postinfection in untreated mice. Rifamycin-containing regimens were superior to isoniazid monotherapy. TMC207 exhibited sterilizing activity at least as strong as that of rifampin alone and similar to that of rifampin + isoniazid, but daily rifapentine +/- isoniazid was superior to TMC207. Addition of TMC207 to rifapentine did not improve the sterilizing activity of rifapentine in this model.CONCLUSIONS:
TMC207 has substantial sterilizing activity and may enable treatment of DR-LTBI in 3-4 months.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinolinas
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Rifampin
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Tuberculosis Latente
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Antibióticos Antituberculosos
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Antituberculosos
Tipo de estudio:
Guideline
Límite:
Animals
Idioma:
En
Año:
2011
Tipo del documento:
Article