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Master of Public Health

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

AUTHORS

Haley CA , Schechter MC , Ashkin D , Peloquin CA , Cegielski JP , Andrino BB , Burgos M , Caloia LA , Chen L , Colon-Semidey A , DeSilva MB , Dhanireddy S , Dorman SE , Dworkin FF , Hammond-Epstein H , Easton AV , Gaensbauer JT , Ghassemieh B , Gomez ME , Horne D , Jasuja S , Jones BA , Kaplan LJ , Khan AE , Kracen E , Labuda S , Landers KM , Lardizabal AA , Lasley MT , Letzer DM , Lopes VK , Lubelchek RJ , Macias CP , Mihalyov A , Misch EA , Murray JA , Narita M , Nilsen DM , Ninneman MJ , Ogawa L , Oladele A , Overman M , Ray SM , Ritger KA , Rowlinson MC , Sabuwala N , Schiller TM , Schwartz LE , Spitters C , Thomson DB , Tresgallo RR , Valois P , Goswami ND , , . Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023 5 30; ().

ABSTRACT

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 1200 mg linezolid. After U.S. FDA approval in 2019, some U.S. clinicians rapidly implemented BPaL using an initial linezolid 600 mg 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.

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