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Ticarcillin-clavulanic acid pharmacokinetics in preterm neonates with presumed sepsis
A H Burstein1, L E Wyble, P Gal
1Division of Neuropharmacology, Dent Neurologic Institute, Millard Fillmore Hospital, Buffalo, New York 14209.
Insights
Current dosing of ticarcillin-clavulanic acid may lead to low clavulanic acid levels in premature infants. A revised regimen of 50 mg/kg every 6 hours is suggested for better therapeutic outcomes in neonates with sepsis.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Infectious Diseases
Background:
- Premature low-birth-weight neonates with presumed sepsis require careful antibiotic management.
- Understanding the pharmacokinetics of antibiotics in this vulnerable population is crucial for effective treatment.
Purpose of the Study:
- To characterize the pharmacokinetics of ticarcillin and clavulanic acid in premature neonates.
- To evaluate the current dosing regimen (75 mg/kg every 12 hours) for ticarcillin-clavulanic acid in this population.
Main Methods:
- Eleven premature neonates (<2,200 g) with presumed sepsis received ticarcillin-clavulanic acid intravenously.
- Blood samples were collected at specified intervals post-infusion for drug concentration analysis.
- Drug concentrations were determined using a microbiologic assay.
Main Results:
- Pharmacokinetic parameters for ticarcillin and clavulanic acid were determined, including clearance and half-life.
- Analysis revealed a high interpatient variability in pharmacokinetic parameters for both drugs.
- Current dosing regimens risk subtherapeutic concentrations of clavulanic acid.
Conclusions:
- The standard 75 mg/kg every 12-hour dosing of ticarcillin-clavulanic acid may be inadequate for premature neonates.
- A revised dosing strategy of 50 mg/kg every 6 hours is proposed as more rational.
- Further studies are warranted to confirm optimal dosing for neonatal sepsis treatment.
Abstract:
The objective of the reported study was to characterize the pharmacokinetics of ticarcillin and clavulanic acid in premature low-birth-weight (less than 2,200 g) neonates with presumed sepsis. Eleven infants received 12 courses of ticarcillin-clavulanic acid at 75 mg/kg of body weight intravenously every 12 h. Blood samples were collected at 0.5, 1.5, 4, and 8 h following the infusion of the initial dose. The concentrations of ticarcillin and clavulanic acid were determined by a microbiologic assay. Median (interpatient coefficients of variation) values for the volume of the central compartment, total steady-state volume, distributional clearance, total clearance, and terminal elimination half-life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%), 0.41 liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), respectively. For clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11 liters/h/kg (36%), 0.12 liters/h/kg (72%), and 1.95 h (40%), respectively. Our results suggest that the current dosing recommendations of 75 mg/kg every 12 h risk subtherapeutic clavulanic acid concentrations and that 50 mg/kg every 6 h is a more rational dosing strategy.