Treatment of drug-resistant tuberculosis with bedaquiline, pretomanid, linezolid with or without moxifloxacin (BPaL/M): Feasibility and implementation challenges in western Canada
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.004 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".