title: (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.
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, USA; Bouvé College of Health Sciences, Northeastern University, Boston, USA.
authors.forename: M
authors.initials: M
authors.lastname: Milstein
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: A
authors.initials: A
authors.lastname: Brzezinski
authors.affiliation: Medical Department, Médecins Sans Frontières, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Varaine
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, USA; Partners In Health, Boston, USA; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Mitnick
mesh_terms: D000284:Administration, Oral; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D064687:Diarylquinolines / Q000008:administration & dosage / Q000627:therapeutic use; D019317:Evidence-Based Medicine; D006801:Humans; D000069349:Linezolid / Q000008:administration & dosage / Q000627:therapeutic use; D009339:Needles; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D010080:Oxazoles / Q000008:administration & dosage / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D009593:Nitroimidazoles; C516022:OPC-67683; D010080:Oxazoles; C493870:bedaquiline; D000069349:Linezolid