(Re)moving the needle: prospects for all-oral treatment for multidrug-resistant tuberculosis.

Abstract

Currently recommended regimens for multidrug-resistant tuberculosis (MDR-TB) contain painful daily injections and are unsuccessful in approximately half of patients. Removal of the injectable agent to fashion all-oral regimens could transform MDR-TB treatment and access to care. To explore evidence for all-oral treatment regimens. We review evidence on drugs that could be included in injection-free MDR-TB regimens. The oral drugs considered have an indication for or are recommended for off-label use for TB or MDR-TB, and have demonstrated bactericidal activity. Drugs with weak bactericidal activity should have limited prior population exposure and evidence of effectiveness in MDR-TB regimens. Bedaquiline, delamanid, and linezolid all display strong bactericidal activity, while clofazimine has weak bactericidal activity. They all have limited prior population exposure and demonstrated effectiveness in MDR-TB regimens. Despite widespread exposure to pyrazinamide and late-generation fluoroquinolones in the population, all are bactericidal and have shown great value when included in treatment regimens for MDR-TB. The evidence supports the use of all-oral regimens comprising new and existing drugs for MDR-TB treatment. Existing evidence of bactericidal activity and efficacy for these drugs provides a convincing argument for transitioning MDR-TB treatment towards all-oral regimens. These new regimens could mitigate the delivery, cost, and adherence challenges inherent to the current standard.