Muir Paige, Cook Victoria J, Sekirov Inna, Johnston James, Connors William J
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Tuberculosis Services, BC Centre for Disease Control, Vancouver, British Columbia, Canada.
J Assoc Med Microbiol Infect Dis Can. 2025 Apr 5;10(2):192-202. doi: 10.3138/jammi-2024-0034. eCollection 2025 Jun.
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.
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.
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).
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.
耐利福平（RR）和耐多药（MDR）结核病（TB）以前需要使用疗程漫长且疗效欠佳的毒性二线抗结核药物进行治疗。目前推荐使用含贝达喹啉、普瑞玛尼、利奈唑胺（含或不含莫西沙星）的新型6个月治疗方案（BPaL/M），但加拿大的实施情况尚无详尽描述。
我们分析了加拿大西部8例接受BPaL/M治疗的耐多药或广泛耐药前期（pre-XDR）结核病患者或利福霉素不耐受患者，以为扩大该方案的使用提供参考。
确认一线和二线结核病表型药敏谱的平均时间分别为5周和11周。从诊断日期起，开始有效治疗方案的平均时间为5周，而由于药物审批、获取和供应延迟，开始使用BPaL/M的时间为11周。从有效治疗开始，培养转阴和涂片转阴的平均时间分别为3周和5周。患者平均隔离15周，平均住院时间为13周。BPaL/M药物与轻微毒性相关，包括轻度非进行性周围神经病变（3例，CTCAE 2级）和因贫血进行输血（3例，CTCAE 3级），所有这些情况均通过调整利奈唑胺剂量进行处理。平均总治疗时长为8个月，截至最后一次随访（平均8个月），所有患者均完成了6个月的BPaL/M治疗，实现了微生物学和临床治愈。
6个月的全口服BPaL/M方案在这些患者中似乎有效，但药敏试验延迟和药物获取困难导致隔离、住院时间延长以及总体治疗时长增加。为了在加拿大充分实现BPaL/M治疗给患者和卫生系统带来的益处，必须优先简化实验室检测和药物获取流程。
