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High gentamicin trough concentrations in neonates of less than 28 weeks gestational age
Insights
Gentamicin dosing in newborns requires careful adjustment based on gestational age (GA) to achieve therapeutic levels. Incorrect dosing can lead to sub-therapeutic or toxic serum concentrations, impacting treatment efficacy and safety.
Area of Science:
- Neonatal Pharmacology
- Pediatric Infectious Diseases
- Clinical Pharmacy
Background:
- Gentamicin is a crucial antibiotic for treating neonatal infections.
- Accurate dosing is essential due to neonates' altered drug metabolism and excretion.
- Gestational age (GA) significantly influences gentamicin pharmacokinetics in newborns.
Purpose of the Study:
- To prospectively evaluate gentamicin serum concentrations in a diverse newborn population.
- To assess the impact of different dosing intervals based on GA on gentamicin levels.
- To identify potential risk factors for altered gentamicin disposition in neonates.
Main Methods:
- Prospective study of 77 newborns with varying gestational ages (25.5-43 weeks).
- Gentamicin administered at 2.5 mg/kg/dose with intervals adjusted by GA (q24h, q18h, q12h).
- Peak and trough serum gentamicin concentrations measured on days 1, 3, and 5 of therapy.
Main Results:
- On day 1, a significant percentage of neonates across different GA groups had sub-therapeutic trough concentrations (<2.0 µg/mL).
- By day 3, neonates <28 weeks GA on q18h dosing showed a higher incidence of elevated trough concentrations (>2.0 µg/mL) compared to q24h dosing (p<0.05).
- Dosing intervals significantly influenced gentamicin serum concentrations, suggesting GA-specific adjustments are necessary.
Conclusions:
- Current gentamicin dosing regimens based on GA may not consistently achieve therapeutic trough concentrations in all neonates.
- The q18h dosing interval for preterm infants (<28 weeks GA) may lead to accumulation.
- Further investigation into optimal gentamicin dosing strategies tailored to neonatal GA and disposition is warranted.
Abstract:
77 newborns, ranging from 25.5 to 43 weeks gestational age (GA) and receiving gentamicin, were studied prospectively over 4 months. Peak and trough serum concentrations were obtained on days 1, 3, and 5 of therapy. Gentamicin, 2.5 mg/kg/dose, was given at intervals according to GA. 63% of newborns of less than 28 weeks on doses of gentamicin of 2.5 mg/kg every 24 h (q24h), 75% of less than 28 weeks on gentamicin q18h, 90% of newborns of 23-34 weeks (on q18h), and 82% of those of greater than 34 weeks GA (on q12h) had serum gentamicin trough concentrations less than or equal to 2.0 micrograms/ml on day 1. By day 3, 5/5 newborns of less than 28 weeks (q18h) had trough concentrations greater than 2.0 micrograms/ml, whereas only 20% of those on the q24h regimen had high trough concentrations (p less than 0.05). Possible risk factors associated with altered gentamicin disposition in neonates are discussed.