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The current drug regimens for treating tuberculosis are lengthy and onerous, and hence complicated by poor adherence leading to drug resistance and disease relapse. Previously, using an output-driven optimization platform and an  in vitro  macrophage model of  Mycobacterium tuberculosis  infection, we identified several experimental drug regimens among billions of possible drug-dose combinations that outperform the current standard regimen. Here we use this platform to optimize the  in vivo  drug doses of two of these regimens in a mouse model of pulmonary tuberculosis. The experimental regimens kill  M. tuberculosis  much more rapidly than the standard regimen and reduce treatment time to relapse-free cure by 75%. Thus, these regimens have the potential to provide a markedly shorter course of treatment for tuberculosis in humans. As these regimens omit isoniazid, rifampicin, fluoroquinolones and injectable aminoglycosides, they would be suitable for treating many cases of multidrug and extensively drug-resistant tuberculosis.

Drug regimens identified and optimized by output-driven platform markedly reduce tuberculosis treatment time