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Randomized, controlled trial comparing once daily and three times daily gentamicin in children with urinary tract
J R Carapetis1, A L Jaquiery, J P Buttery
1Department of Microbiology and Infectious Diseases, Royal Children's Hospital, University of Melbourne, Australia.
Insights
Once daily gentamicin dosing is safe and effective for treating severe pediatric urinary tract infections (UTI). This regimen achieves optimal gentamicin concentrations, with no observed nephrotoxicity or ototoxicity in children.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacokinetics and Pharmacodynamics
- Antimicrobial Stewardship
Background:
- Severe urinary tract infections (UTI) in children often require parenteral antibiotic therapy.
- Gentamicin is a common antibiotic used for severe UTIs, but optimal dosing strategies are crucial.
- Traditional three times daily (TD) dosing may lead to sub-therapeutic peak concentrations and potential toxicity.
Purpose of the Study:
- To evaluate the safety and efficacy of once daily (OD) gentamicin dosing in children with severe UTI.
- To perform population pharmacokinetic modeling to understand gentamicin disposition in this population.
- To compare OD gentamicin with TD gentamicin in pediatric patients.
Main Methods:
- An open-label, randomized controlled trial was conducted in hospitalized children aged 1 month to 12 years with UTI.
- Participants received either OD or TD gentamicin, with age-adjusted daily doses.
- Population pharmacokinetic modeling was used to analyze gentamicin concentrations.
Main Results:
- 179 children were enrolled (90 OD, 89 TD).
- OD gentamicin achieved significantly higher peak concentrations (17.3 mg/l vs. 6.4 mg/l) and lower trough concentrations (0.35 mg/l vs. 0.55 mg/l) compared to TD.
- No clinical or bacteriologic failures were observed, and no nephrotoxicity or ototoxicity was identified.
Conclusions:
- Once daily gentamicin dosing is a safe and effective strategy for treating severe pediatric UTI requiring parenteral therapy.
- Age-appropriate dosing and monitoring of serum trough concentrations are essential for optimizing OD gentamicin therapy.
- This dosing regimen ensures therapeutic gentamicin levels while minimizing toxicity risks in children.
Objective:
To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily (OD) gentamicin dosing in children with severe urinary tract infections (UTI).
Methods:
An open, randomized, controlled trial comparing OD with three times daily (TD) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI. Daily doses (milligrams per kg per day) of gentamicin in both groups were 7.5 (<5 years old), 6.0 (5 to 10 years old) and 4.5 (>10 years old).
Results:
There were 179 children enrolled (90 OD, 89 TD). Baseline clinical characteristics and pathogens were similar, except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group. Median gentamicin treatment durations were 3.0 (OD) and 2.7 (TD) days. Mean peak gentamicin concentrations were 17.3 (OD) vs. 6.4 (TD) mg/l; 99% of peak concentrations were >7 mg/l in the OD group whereas 16% of peak concentrations were <5 mg/l in the TD group. Mean trough concentrations were 0.35 (OD) vs. 0.55 (TD) mg/l. In the OD group 4% of trough concentrations were > or = 2 mg/l, whereas in the TD group only 0.7% were > or = 2 mg/l. Age or prior elevated peak concentrations did not predict high trough concentrations. Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination. There were no clinical or bacteriologic failures. The two disease-related complications were confined to the OD group. No nephro- or ototoxicity was identified.
Conclusions:
With age-appropriate dosing and measurement of serum trough concentrations before the second dose, OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years.