PURPOSE OF REVIEW: For the first time in decades, there are multiple new drugs in the pipeline for the treatment of tuberculosis (TB). In addition, existing drugs are being repurposed or optimized for TB with the goal of shortened treatment duration for drug-sensitive TB and safer, shorter treatments for multidrug-resistant (MDR) TB. In this review, the results of recent trials evaluating novel combination regimens for TB disease and latent TB infection are described. RECENT FINDINGS: High-dose rifamycins (rifampin and rifapentine) and fluoroquinolones directly observed have treatment-shortening potential when used for drug-sensitive TB disease, and a 12-dose once-weekly regimen of rifapentine along with isoniazid effectively treats latent TB. Bedaquiline, an anti-TB drug with a novel mechanism of action, and delamanid, a nitroimidazole, are entering phase 3 trials. Both improve rates of sputum culture conversion among patients with MDR-TB. Other nitroimidazoles and oxazolidinones are in Phase 2 testing, as are combinations involving multiple new chemical entities. SUMMARY: With the resurgence of anti-TB drug discovery efforts, we now have a modestly robust pipeline of new anti-TB drugs. Several promising new regimens involving investigational and existing drugs that may be capable of shortening treatment for drug-sensitive TB and improving management of drug-resistant TB are in late-phase clinical evaluation.
PURPOSE OF REVIEW: For the first time in decades, there are multiple new drugs in the pipeline for the treatment of tuberculosis (TB). In addition, existing drugs are being repurposed or optimized for TB with the goal of shortened treatment duration for drug-sensitive TB and safer, shorter treatments for multidrug-resistant (MDR) TB. In this review, the results of recent trials evaluating novel combination regimens for TB disease and latent TB infection are described. RECENT FINDINGS: High-dose rifamycins (rifampin and rifapentine) and fluoroquinolones directly observed have treatment-shortening potential when used for drug-sensitive TB disease, and a 12-dose once-weekly regimen of rifapentine along with isoniazid effectively treats latent TB. Bedaquiline, an anti-TB drug with a novel mechanism of action, and delamanid, a nitroimidazole, are entering phase 3 trials. Both improve rates of sputum culture conversion among patients with MDR-TB. Other nitroimidazoles and oxazolidinones are in Phase 2 testing, as are combinations involving multiple new chemical entities. SUMMARY: With the resurgence of anti-TB drug discovery efforts, we now have a modestly robust pipeline of new anti-TB drugs. Several promising new regimens involving investigational and existing drugs that may be capable of shortening treatment for drug-sensitive TB and improving management of drug-resistant TB are in late-phase clinical evaluation.
Authors: A H Diacon; P R Donald; A Pym; M Grobusch; R F Patientia; R Mahanyele; N Bantubani; R Narasimooloo; T De Marez; R van Heeswijk; N Lounis; P Meyvisch; K Andries; D F McNeeley Journal: Antimicrob Agents Chemother Date: 2012-03-05 Impact factor: 5.191
Authors: Kapil Tahlan; Regina Wilson; David B Kastrinsky; Kriti Arora; Vinod Nair; Elizabeth Fischer; S Whitney Barnes; John R Walker; David Alland; Clifton E Barry; Helena I Boshoff Journal: Antimicrob Agents Chemother Date: 2012-01-17 Impact factor: 5.191
Authors: Ramesh Jayaram; Sheshagiri Gaonkar; Parvinder Kaur; B L Suresh; B N Mahesh; R Jayashree; Vrinda Nandi; Sowmya Bharat; R K Shandil; E Kantharaj; V Balasubramanian Journal: Antimicrob Agents Chemother Date: 2003-07 Impact factor: 5.191
Authors: Ramandeep Singh; Ujjini Manjunatha; Helena I M Boshoff; Young Hwan Ha; Pornwaratt Niyomrattanakit; Richard Ledwidge; Cynthia S Dowd; Ill Young Lee; Pilho Kim; Liang Zhang; Sunhee Kang; Thomas H Keller; Jan Jiricek; Clifton E Barry Journal: Science Date: 2008-11-28 Impact factor: 63.714
Authors: Ian M Rosenthal; Ming Zhang; Kathy N Williams; Charles A Peloquin; Sandeep Tyagi; Andrew A Vernon; William R Bishai; Richard E Chaisson; Jacques H Grosset; Eric L Nuermberger Journal: PLoS Med Date: 2007-12 Impact factor: 11.069
Authors: Melissa R Nyendak; David M Lewinsohn; Raj D Shah; Richard G Wunderink; Carl D Koch; Alison Morris; Kolene E McDade; Gaetane C Michaud; Amit K Mahajan; Colleen L Channick; A Christine Argento; Momen M Wahidi; William S Beckett; Gautam George; Carey C Thomson Journal: Ann Am Thorac Soc Date: 2014-09
Authors: Vincent P DeMarco; Alvaro A Ordonez; Mariah Klunk; Brendan Prideaux; Hui Wang; Zhang Zhuo; Peter J Tonge; Robert F Dannals; Daniel P Holt; Carlton K K Lee; Edward A Weinstein; Véronique Dartois; Kelly E Dooley; Sanjay K Jain Journal: Antimicrob Agents Chemother Date: 2015-07-13 Impact factor: 5.191
Authors: Helen S Cox; Jennifer J Furin; Carole D Mitnick; Colleen Daniels; Vivian Cox; Eric Goemaere Journal: Bull World Health Organ Date: 2015-05-15 Impact factor: 9.408