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U.S. Implementation of BPaL: An All-Oral Treatment Regimen for Drug-Resistant TB

– An IDSA Reading Room selection

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 Colon-Semidey, Malini B DeSilva, Shireesha Dhanireddy, Susan E Dorman, Felicia F Dworkin, Heidi Hammond-Epstein, Alice V Easton, James T Gaensbauer, Bijan Ghassemieh, Maria E Gomez, David Horne, Supriya Jasuja, Betsy A Jones, Leonard J Kaplan, Asharaf Edward Khan, Elizabeth Kracen, Sarah Labuda, Karen M Landers, Alfred A Lardizabal, Maria T Lasley, David M Letzer, Vinicius K Lopes, Ronald J Lubelchek, C Patricia Macias, Aimee Mihalyov, Elizabeth Ann Misch, Jason A Murray, Masahiro Narita, Diana M Nilsen, Megan J Ninneman, Lynne Ogawa, Alawode Oladele, Melissa Overman, Susan M Ray, et al.

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This is an abstract. The full journal study is available to read via the link in the source information below.

Background

Rifampin-resistant tuberculosis (TB) 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 FDA approval in 2019, some U.S. clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring.

Methods

Data from U.S. patients treated with BPaL between October 14, 2019 and April 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 patients 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 the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by TDM and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, three patients (4.4%) with hematologic toxicity and three (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 TB. In this cohort, effective treatment required less than half the duration recommended in 2019 U.S. 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 TB treatments in the United States is feasible.

Read an interview about the study here.

The full text of this study can be accessed via the source information below.

Primary Source

Clinical Infectious Diseases

Source Reference:

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