Implementation of bpal in the United States: Experience using a novel all-oral treatment regimen for treatment of rifampin-resistant or rifampin-intolerant TB disease

Details

• Alternative Title:
  Clin Infect Dis
• Personal Author:
  Haley, Connie A ; Schechter, Marcos C ; Ashkin, David ; Peloquin, Charles A ; Cegielski, J. Peter ; Andrino, Barbara B. ; Burgos, Marcos ; Caloia, Lori A. ; Chen, Lisa ; Colon-Semidey, Angel ; DeSilva, Malini B. ; Dhanireddy, Shireesha ; Dorman, Susan E ; Dworkin, Felicia F. ; Hammond-Epstein, Heidi ; Easton, Alice V. ; Gaensbauer, James T. ; Ghassemieh, Bijan ; Gomez, Maria E. ; Horne, David ; Jasuja, Supriya ; Jones, Betsy A. ; Kaplan, Leonard J. ; Khan, Asharaf Edward ; Kracen, Elizabeth ; Labuda, Sarah ; Landers, Karen M. ; Lardizabal, Alfred A. ; Lasley, Maria T ; Letzer, David M. ; Lopes, Vinicius K. ; Lubelchek, Ronald J. ; Macias, C. Patricia ; Mihalyov, Aimee ; Misch, Elizabeth Ann ; Murray, Jason A. ; Narita, Masahiro ; Nilsen, Diana M. ; Ninneman, Megan J. ; Ogawa, Lynne ; Oladele, Alawode ; Overman, Melissa ; Ray, Susan M. ; Ritger, Kathleen A. ; Rowlinson, Marie-Claire ; Sabuwala, Nadya ; Schiller, Thomas M. ; Schwartz, Lawrence E. ; Spitters, Christopher ; Thomson, Douglas B. ; Tresgallo, Rene Rico ; Valois, Patrick ; Goswami, Neela D.
• Corporate Authors:
  For the BPaL Implementation Group
• Description:
  Background:
  
  Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons initiate treatment and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, six-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200mg linezolid. After U.S. FDA approval in 2019, some U.S. clinicians rapidly implemented BPaL using an initial linezolid 600mg dose adjusted by serum drug concentrations and clinical monitoring.
  
  Methods:
  
  Data from U.S. patients treated with BPaL between 10/14/2019 and 4/30/2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider-driven, and most had linezolid adjusted by therapeutic drug monitoring (TDM).
  
  Results:
  
  Of 70 patients starting BPaL, two changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and two of these 68 (2.9%) patients relapsed after completion. Using an initial 600 mg linezolid dose daily adjusted by TDM and careful clinical and laboratory monitoring for side effects, supportive care, and expert consultation throughout BPaL treatment, three (4.4%) patients with hematologic toxicity and four (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months.
  
  Conclusions:
  
  BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in ATS/CDC/ERS/IDSA 2019 guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the U.S. is feasible.
  
  
• Subjects:
  Antitubercular Agents Diarylquinolines Humans Linezolid Rifampin Tuberculosis Tuberculosis, Multidrug-Resistant United States
• Keywords:
  Bedaquiline Drug Resistance Linezolid Pretomanid
• Source:
  Clin Infect Dis. 77(7):1053-1062
• Pubmed ID:
  37249079
• Pubmed Central ID:
  PMC11001496
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/ ; K23 AI135102/AI/NIAID NIH HHSUnited States/
• Volume:
  77
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:892a9ea63ecf93125095670fe0223585088b19ea086c3c91b16ad8ccb7daee895708e27d8e7adbfa366af17b3d90deefa7ff8b03afc9f2b5d20141d3ef143053
• Download URL:
  https://stacks.cdc.gov/view/cdc/154140/cdc_154140_DS1.pdf
• File Type:
  [PDF - 144.70 KB ]