Bactericidal and sterilizing activity of a novel regimen with bedaquiline, pretomanid, moxifloxacin and pyrazinamide in a murine model of tuberculosis [PublishAheadOfPrint]

New regimens based on two or more novel agents are sought to shorten or simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) + pretomanid (PMD) + pyrazinamide (PZA) and of PMD + moxifloxacin (MXF) + PZA shorten the treatment duration necessary to prevent relapse by 2-3 and 1-2 months, respectively, compared with the current first-line regimen in a murine TB model. These 3-drug combinations are now being studied in clinical trials. Here, the 4-drug combination of BDQ+PMD+MXF+PZA was compared to its 3-drug component regimens and different treatment durations of PZA and MXF were explored to identify the optimal regimens and treatment times and to infer the likelihood of success against drug-resistant strains. BDQ+PMD+MXF+PZA rendered all mice relapse free after two months of treatment. PZA could be discontinued after the first month of treatment without worsening outcomes, whereas the absence of MXF, PZA or BDQ from the beginning required approximately 0.5, 1 or 2 months of additional treatment to attain the same outcome.

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