Fully weekly antituberculosis regimen: a proof-of-concept study.

BACKGROUND: WHO recommends supervising the treatment of tuberculosis. Intermittent regimens have the potential to simplify the supervision and improve compliance. Our objective was to analyse the sterilising activity of once-weekly regimens based on drugs with a long half-life, bedaquiline and rifapentine, in a murine model of tuberculosis. METHODS: 300 Swiss mice were intravenously infected with 10exp6 Colony Forming Unit (CFU) of Mycobacterium tuberculosis H37Rv. Mice were treated once-weekly by regimens containing: a) bedaquiline, rifapentine and pyrazinamide (BPZ); b) BPZ plus moxifloxacin (BPZM); c) BPZM plus clofazimine (BPZMC); d) the standard daily regimen of tuberculosis. All regimens were given for 4 or 6 months. Bactericidal and sterilising activity were assessed. RESULTS: After 2 months of treatment, the mean log10 CFU count in lungs was 0.76±0.60 log10 in mice treated by the daily control regimen and negative in all mice treated by once-weekly regimens (p 0.05 for all once-weekly regimens versus 6-month daily control). CONCLUSIONS: BPZ-based once-weekly regimens have higher sterilising activity than the standard daily regimen and could greatly simplify treatment administration and possibly shorten the duration of tuberculosis treatment.