Aerosolization of Second-generation Triazoles: In Vitro Evaluation and Application in Therapy of Invasive Airway Aspergillosis
Bibliographic record
Abstract
BACKGROUND: A lung transplant patient with invasive aspergillosis (IA) manifested symptoms of voriconazole-induced transaminitis with systemic voriconazole and progression of IA after switching to oral posaconazole. With limited options for standard triazole therapy, aerosolized delivery with one of the second-generation triazoles was considered. METHODS: Feasibility for aerosolized delivery was evaluated using cascade impactor and analysis of physicochemical characteristics of voriconazole (10 mg/mL) and posaconazole (6, 12 mg/mL) solutions. RESULTS: Both triazoles showed favorable characteristics for aerosol delivery with mass median aerodynamic diameter, geometric standard deviation, respirable fraction (<5.4 µm) of 2.8 µm, 2.0, 86%; 3.4 µm, 2.4, 78%; and 3.0 µm, 2.3, 79% for voriconazole and 6, 12 mg/mL of posaconazole, respectively. Aspergillus fumigatus isolate from the patient was more susceptible to voriconazole, and hence aerosolized voriconazole was introduced around the third month posttransplant at 40 mg TID for 1 week, 40 mg BID for 1 week, followed by 40 mg daily thereafter, along with IV caspofungin (50 mg/d) and liposomal amphotericin B (300 mg/d). The aerosol regimen was well tolerated by the patient with undetectable trough plasma levels of voriconazole. Bronchoscopy at the fourth month revealed improvement in anastomotic plaques with reduction in bronchoalveolar lavage galactomannan values (7.48-2.15 ng/mL). This consolidated aerosolized and intravenous regimen was maintained until 2.97 years posttransplant. CONCLUSIONS: The intravenous solutions of both second-generation triazoles showed characteristics that were suitable for aerosol delivery. Our report further adds to the therapeutic experience with the use of aerosolized voriconazole for IA in a lung transplant patient.
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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 | 0.000 | 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".