Long‐Term Azithromycin Therapy in Cystic Fibrosis Patients: A Study on Drug Levels and Sputum Properties
Bibliographic record
Abstract
BACKGROUND: Following reports on the treatment of diffuse panbronchiolitis (DPB), recent studies demonstrate that long term therapy with azithromycin (AZM) is effective in cystic fibrosis (CF) patients. However, the underlying mechanisms remain uncertain. Some macrolides, including AZM, display inhibition of virulence factors and other antipseudomonal effects at subinhibitory levels in vitro. OBJECTIVES: Drug doses used for CF and DPB therapy were investigated to determine whether they achieve corresponding sputum drug levels in CF patients in vivo. METHODS: In an open, prospective study, 14 CF patients with chronic Pseudomonas aeruginosa airway infection received 250 mg AZM either daily ('high dose') or twice weekly ('low dose') for 12 weeks. Viscoelasticity of sputum was assessed by magnetic microrheology. RESULTS: AZM accumulated in sputum by two orders of magnitude over a period of four weeks. In the following steady state, median AZM concentrations in sputum were 9.5 microg/mL (0.6 to 79.3 microg/mL, interquartiles 1.4 to 33.4 microg/mL) and 0.5 microg/mL (range less than 0.1 [below detection level] to 5.2 microg/mL, interquartiles 0.2 to 1.4 microg/mL) in the high and low dose groups, respectively. Viscoelasticity improved in all patients but one. CONCLUSIONS: The findings suggest that antipseudomonal activity has to be considered among the potential mechanisms of macrolide therapy. Further, viscoelasticity may be a valuable parameter in future clinical trials.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".