Fully weekly antituberculosis regimen: a proof-of-concept study.
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.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.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 compared to the daily control). All mice had negative lung cultures on completion of either 4 or 6 months of treatment, whereas 3 months after 4 and 6 months of treatment respectively, the relapse rate was 64% and 13% in the standard daily regimen, 5% and 0% in BPZ, 0% and 0% in BPMZ and 0% and 5% in BPMZC (p<0.05 for all once-weekly regimens versus 4-month daily control, p>0.05 for all once-weekly regimens versus 6-month daily control).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.