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Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease

2023; Oxford University Press; Volume: 77; Issue: 7 Linguagem: Inglês

10.1093/cid/ciad312

1537-6591

Connie A. Haley, Marcos C. Schechter, David Ashkin, Charles A. Peloquin, J. Peter Cegielski, Barbara B Andrino, Marcos Burgos, Lori A Caloia, Lisa Chen, Angel Colón‐Semidey, Malini B. DeSilva, Shireesha Dhanireddy, Susan E. Dorman, Felicia Dworkin, Heidi Hammond-Epstein, Alice V. Easton, James Gaensbauer, Bijan J. Ghassemieh, María Elena Gómez, David Horné, Supriya Jasuja, Betsy A. Jones, Leonard J. Kaplan, Asharaf Edward Khan, Elizabeth Kracen, Sarah M. Labuda, Karen M. Landers, Alfred Lardizabal, Maria T Lasley, David Letzer, Vinicius K Lopes, Ronald Lubelchek, C. Patricia Macias, Aimee Mihalyov, Elizabeth Ann Misch, Jason A. Murray, Masahiro Narita, Diana Nilsen, M.J. Ninneman, Lynne Ogawa, Alawode Oladele, Melissa C Overman, Susan M. Ray, Kathleen A. Ritger, Marie‐Claire Rowlinson, Nadya Sabuwala, Thomas M Schiller, Lawrence E. Schwartz, Christopher Spitters, Douglas B Thomson, Rene Rico Tresgallo, Patrick Valois, Neela D. Goswami, Rocio Agraz-Lara, Amina Ahmed, Ana Alvarez, Lisa Armitage, Pennan M. Barry, Robert Belknap, John Bernardo, Mary Bravo, Sarah K. Brode, Elizabeth Burden, Joseph Burzynski, Caralee Caplan‐Shaw, Ken Castro, Terry Chorba, William Connors, Victoria Cook, Andrea T. Cruz, Charles L. Daley, Shom Dasgupta, Sonia Dhingra, Thomas Dobbs, Ellen Elmore, Frank Erwin, Vincent Escuyer, Christina T. Fiske, Beth Gadkowski, Germán Henestroza, Julie Higashi, Shereen Katrak, Chris Keh, Amanda Khalil, Lilian Kigonya, Michael Lauzardo, Sapna Bamrah Morris, Sonal S. Munsiff, Scott A. Nabity, Margaret J. Oxtoby, Amee Patrawalla, Allison L. Phillips, Ann Raftery, Caitlin Reed, Brian Rock, Kelly Russo, Harleen Sahini, Paul Saleeb, Roberto P. Santos, Barbara Seaworth, Joanna Shaw-Kaikai, J R Starke, Jason E. Stout, Wesley Stubblefield, Zelalem Temesgen, Keziah Thomas, Jeffrey A. Tornheim, Caryn M. Upton, Daniel Urbine, Shuhua Wang, Jon Warkentin, Risa M. Webb, John Wilson, Johnathan Wortham, and Salinia Yu, C. A. Altman, Irfan Hafiz, Deepa Prabhakar, William Bowler,

Antimicrobial Resistance in Staphylococcus

Abstract Background Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. Methods Data from US patients treated with BPaL between 14 October 2019 and 30 April 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 patients had linezolid adjusted by therapeutic drug monitoring. Results Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (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 2019 US 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 United States is feasible.