A Pharmacokinetic Validation Study of Once Daily Dosing of Intravenous Gentamicin and Tobramycin in Pediatric Patients
Bibliographic record
Abstract
Background. Aminoglycosides are commonly used for treating serious infections caused by Gram-negative organisms. Despite evidence to support once daily dosing in the adult population, there is limited experience in children. We aimed to evaluate the ability of a daily dose of 9 mg/kg of intravenous gentamicin and tobramycin to achieve target maximum concentration (Cmax) range of 16-25 mg/L in pediatric patients in our institution. Methods. This retrospective observational cohort study assessed children receiving gentamicin or tobramycin. Pharmacokinetic parameters were calculated using serum levels drawn 3 hours and 6 hours after a dose of aminoglycoside. Descriptive statistics and Monte Carlo simulations were used in our analysis. Results. One hundred and forty seven children with 153 aminoglycoside courses aged 2 months to 18 years were included. Majority of patients were admitted to surgical units (63.4%). Seventy one percent of aminoglycoside courses were indicated for empiric use, 24% for microbiologically documented infections, and 5% for prophylaxis. Mean population pharmacokinetic parameters were: volume of distribution of 0.51 ± 0.28 L/kg, clearance of 2.83 ± 1.33 mL/min/kg and half-life of 2.13 ± 0.65 h. With first dose of therapy, 44.3% of all courses reached target therapeutic Cmax range. The mean Cmax of gentamicin and tobramycin was 18.65 ± 7.78 mg/L. Monte Carlo simulations demonstrated a minimal increase in proportion of simulated patients achieving target Cmax range with a dose increase from 9 mg/kg to 10 mg/kg (33.5% versus 33.7%, respectively). Ninety-three percent of patients defervesced by end of treatment course. The median change from baseline for: white blood cell count was −16.46% (interquartile range (IQR): −37.32 to 9.41), serum creatinine was 5.84% (IQR: −10.96 to 19.18), blood urea nitrogen was 2.27% (IQR: −28.57 to 73.03), and urine output was −13.37% (IQR: −42.02 to 24.51). One patient had audiometry testing, which was normal. Conclusion. An initial gentamicin or tobramycin daily dose of 9 mg/kg is appropriate to achieve target Cmax range and appears to be efficacious and safe for pediatric patients. Monitoring serum aminoglycoside concentrations remains an important strategy to optimize dose for efficacy and safety. Disclosures. All authors: No reported disclosures.
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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 | 0.002 | 0.007 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".