Time to Positive Culture Detection Predicts <i>Mycobacterium avium</i> Pulmonary Disease Severity and Treatment Initiation
Bibliographic record
Abstract
Abstract Rationale Additional biomarkers are needed to guide initiation of treatment for Mycobacterium avium pulmonary disease (Mav-PD). Time to positive sputum culture detection (TTP) may offer potential prognostic and monitoring value. Objectives To determine whether TTP is associated with infection severity and early treatment response in Mav-PD. Methods We undertook a retrospective cohort study of patients with two or more sputum cultures positive for M. avium, an “index” sputum M. avium isolate during 2015–2019, a computed tomographic scan within 6 months, and no treatment for at least 6 months before index sputum. TTP was estimated from the date of laboratory receipt of the specimen to the date of culture positivity confirmation. TTP was tested for association with markers of infection severity (Mav-PD, bronchiectasis, cavitary disease, treatment initiation by 3 and 6 months, and acid fast bacilli [AFB] smear) and treatment response using Mann-Whitney U, Spearman’s correlation coefficient, and Wilcoxon signed-rank tests. We explored a threshold TTP that could identify significant M. avium disease. Results We included 125 patients with mean (standard deviation) age 68.5 (12.5) years and 65% fulfilled disease criteria. Median TTP was 12 (interquartile range 10–15; range 6–44) days. TTP and AFB smear grade were negatively correlated (ρ −0.58; P < 0.001). TTP was associated with nontuberculous mycobacteria (NTM) disease (P = 0.03), AFB smear positivity (P < 0.001), and treatment initiation by 3 (P = 0.01) and 6 (P = 0.03) months. A threshold TTP of 10 days or less was associated with Mav-PD (80.6% vs. 58.4%; ð [95% confidence interval (CI)] 22.1% [5.6–38.6%]; P = 0.02), AFB smear positivity (83.3% vs. 20.2%, ð [95% CI] 63.1% [48.3–77.9%]; P < 0.001), treatment by 3 (38.9% vs. 13.5%; ð [95% CI] 25.4% [8.0–42.8%]; P = 0.003) and 6 (47.2% vs. 19.1%; ð [95% CI] 28.1% [9.9–46.4%]; P = 0.003) months. After 3 and 6 months of treatment, the median (interquartile range) change in TTP was 8 (1 undefined; P < 0.001) and 7 (0 undefined; P = 0.001) days, respectively. Conclusions TTP is associated with bacterial burden and infection severity and increases in response to treatment. A threshold of 10 days or less may be useful in predicting significant Mav-PD. As a readily available biomarker, further exploration of TTP is imperative.
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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 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".