Voriconazole therapeutic drug monitoring among lung transplant recipients receiving targeted therapy for invasive aspergillosis
Bibliographic record
Abstract
BACKGROUND: Voriconazole is the first line treatment for invasive aspergillosis (IA) Current guidelines suggest performing regular voriconazole therapeutic drug monitoring (TDM) to optimize treatment efficacy. We aimed to determine if TDM was predictive of clinical outcome in LTRs. METHODS: Retrospective chart review was performed for all LTRs with probable or proven IA, treated with voriconazole monotherapy and who underwent TDM during therapy. Clinical outcome and toxicity were measured at 12 weeks. Classification and regression tree (CART) analysis was used to determine the most predictive voriconazole level thresholds for successful outcome. RESULTS: One hundred and eighteen TDM samples from 30 LTRs with IA were analyzed. Three LTRs were excluded due to early treatment discontinuation. The median TDM level was 1.2 μg/ml (range 0.06-7.3). At 12 weeks, 62% (17/27) of patients had a successful outcome, while 37% (10/27) of patients failed therapy. CART analysis determined that the best predictor for successful outcome was a median TDM level >0.72 μg/ml. Seventy percent (14/20) of patients with median TDM above 0.72 μg/ml had a successful outcome, compared to 42.9% (3/7) of patients with a median TDM below 0.72 μg/ml (OR 3.11; 95% CI: 0.53-20.4; P = 0.21). CART analysis determined that a TDM level greater than 2.13 μg/ml was predictive of hepatotoxicity. CONCLUSIONS: Our data suggests that a voriconazole TDM range between 0.72 μg/ml and 2.13 μg/ml may be associated with improved outcomes. Our study is in line with current recommendations on the use of voriconazole TDM in improving outcome and minimizing toxicity in LTR with IA.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| 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".