Treatment of pre-extensively drug-resistant tuberculosis in a critically ill patient using bedaquiline, pretomanid, and linezolid therapy in Canada: A case report

Background: Pre-extensively drug-resistant tuberculosis (pre-XDR-TB) infections are rare in Canada. Drug therapies to treat pre-XDR TB are limited and acquisition of World Health Organization guideline regimens that are not marketed in Canada pose delays in patient care. Our report describes the case of a critically ill patient with pre-XDR TB and their journey to recovery using bedaquiline, pretomanid, and linezolid (BPaL) therapy. Methods: In 2024, a 20-year-old international student from India with no past medical history presented to hospital complaining of respiratory symptoms and had evidence of cavitary findings on chest imaging. While hospitalized, sputum samples reported acid fast bacilli (AFB) on smear. Subsequently, Mycobacterium tuberculosis complex DNA was detected using molecular methods and confirmed in culture. Results: The standard four-drug regimen was initiated after the positive AFB report. Upon staged availability of drug susceptibility results, drug therapy was altered as the strain was resistant to the entire empiric regimen. Due to challenges in the early detection of resistance, the patient clinically worsened resulting in mechanical ventilation. The patient was converted from four-drug intravenous therapy to BPaL therapy obtained through Health Canada's Special Access Program on hospital day 70. The patient reached non-infectious status on hospital day 200. Conclusion: This case highlights clinical challenges encountered in the management of pre-XDR TB in Canada and describes the successful use of BPaL therapy in a mechanically ventilated patient.