Evaluation of voriconazole therapeutic drug monitoring in malignant hematology patients
Bibliographic record
Abstract
IntroductionMalignant hematology (MH) patients are susceptible to invasive fungal infections due to prolonged neutropenia and immunosuppressive therapies, which may require voriconazole therapy. Although voriconazole therapeutic drug monitoring (TDM) is common, evidence describing this practice is limited. The primary objective of this study was to describe the current practice of voriconazole TDM in MH patients at the Princess Margaret Cancer Centre (PM).MethodsA retrospective chart review was conducted for MH inpatients initiated on voriconazole at PM between November 1st, 2019 and November 13th, 2020. Data regarding voriconazole doses, levels, dose changes, and adverse effects were collected. The primary endpoint was the proportion of patients with initial voriconazole levels within therapeutic range (1-5 mg/L).ResultsFifty-six patients were included in the study. The most common reason for starting voriconazole was possible invasive fungal infection (44 patients, 78.6%). Fifty-one patients (91.1%) received a loading dose of voriconazole, averaging 386.5 ± 78.5 mg. The average maintenance dose was 242.1 ± 45.7 mg. An average of 2.6 ± 2.9 levels were drawn per patient with an average level of 3.2 ± 2.4 mg/L. Forty-one patients (73.2%) had an initial voriconazole level within therapeutic range and 90 out of 145 total levels (62.1%) were within therapeutic range. There were 52 dose modifications made; 31 (60.8%) doses adjusted, 12 (23.5%) doses held, and 9 (17.6%) doses discontinued. For the 31 dose adjustments, 26 (83.9%) had a level redrawn and 17 (65.4%) of those levels were within therapeutic range. Twenty-three (41.1%) patients developed adverse effects, 8 (34.8%) of which were associated with supratherapeutic levels. Of these 23 patients, 19 (33.9%) experienced transaminitis, 3 (5.4%) experienced both transaminitis and neurotoxicity, and 1 (1.8%) experienced photopsia.ConclusionOverall, 41 (73.2%) patients achieved an initial voriconazole level within therapeutic range. Of these 41 patients, 30 (73.2%) remained within therapeutic range for the duration of their inpatient voriconazole therapy. These findings suggest that the current practice of voriconazole TDM at our institution is yielding largely positive results, but still has room for improvement.
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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 | 0.007 | 0.002 |
| 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 | 0.001 |
| 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".