Abstract
BACKGROUND: Rifampin-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB) previously required treatment with a protracted course of toxic second-line TB drugs with suboptimal efficacy. Novel 6-month regimens of bedaquiline, pretomanid, linezolid with or without moxifloxacin (BPaL/M) are now recommended, but implementation in Canada is not well described. METHODS: We analyzed eight people with MDR or pre-extensively drug-resistant (pre-XDR) TB or rifamycin intolerance treated with BPaL/M in western Canada to inform expanded use. RESULTS: The mean times to confirm first- and second-line phenotypic TB susceptibility profiles were 5 and 11 weeks, respectively. Time to start an effective treatment regimen took on average 5 weeks from date of diagnosis, and time to start BPaL/M took 11 weeks due to medication approval, access, and delivery delays. The mean time to culture and smear conversion was 3 and 5 weeks, respectively, from the start of effective therapy. Individuals were isolated for a mean of 15 weeks with an average duration of hospitalization of 13 weeks. BPaL/M medications were associated with minor toxicity, including mild non-progressive peripheral neuropathy (3 cases, CTCAE grade 2) and blood transfusion for anemia (3 cases, CTCAE grade 3), all managed by linezolid dose adjustments. The mean total treatment duration was 8 months, and all individuals completed 6-month BPaL/M treatment with microbiological and clinical cure as of last follow-up (mean 8 months). CONCLUSIONS: Six-month all-oral BPaL/M regimens appeared effective in these individuals, but delays in drug susceptibility testing and poor medication access led to prolonged isolation, hospitalizations, and overall treatment duration. To fully realize the patient and health system benefits of BPaL/M treatment in Canada, streamlining laboratory testing and medication access must be prioritized.