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Pharmacokinetics of ceftriaxone in neonates and infants with meningitis
Insights
Ceftriaxone
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pediatric Infectious Diseases
- Neonatal Pharmacology
Background:
- Ceftriaxone is a crucial antibiotic for treating serious infections in neonates and infants.
- Understanding ceftriaxone pharmacokinetics in this population is vital for optimizing dosing and ensuring efficacy.
- Cerebrospinal fluid (CSF) penetration is critical for meningitis treatment.
Purpose of the Study:
- To investigate the pharmacokinetics of ceftriaxone in neonates and infants with meningitis.
- To evaluate the influence of age on ceftriaxone's total body clearance, volume of distribution, and half-life.
- To quantify ceftriaxone penetration into the cerebrospinal fluid (CSF).
Main Methods:
- Pharmacokinetic analysis of ceftriaxone in plasma, urine, and CSF samples.
- Dosing regimens included 50 mg/kg/day for neonates <14 days and 100 mg/kg/day for older patients.
- Comparison of CSF and plasma concentration-time curves to determine CSF penetration.
Main Results:
- Significant age-dependent differences in ceftriaxone total body clearance (ClT) and half-life (t 1/2) were observed.
- Neonates (<1 week) had lower ClT (0.37 ml/min/kg) and longer t 1/2 (16.2 hours) compared to older neonates and infants.
- Mean ceftriaxone CSF penetration was 17% in bacterial meningitis, reaching concentrations above minimum inhibitory levels.
Conclusions:
- Ceftriaxone elimination is less developed in very young neonates, necessitating careful dose consideration.
- Adequate CSF penetration of ceftriaxone in bacterial meningitis suggests therapeutic efficacy.
- Age significantly impacts ceftriaxone pharmacokinetics in pediatric patients.
Abstract:
The pharmacokinetics of ceftriaxone was studied in the plasma, urine, and cerebrospinal fluid of seven neonates and seven infants with meningitis. In addition, plasma and urine data were obtained in five neonates and one infant receiving ceftriaxone for other serious infections. All neonates younger than 14 days received daily doses of 50 mg/kg ceftriaxone; all other patients but two received 100 mg/kg. The average weight-corrected values for total body clearance (ClT), volume of distribution (Vdss), and biologic half-life (t 1/2) were 0.37 ml/min/kg, 0.45 L/kg, and 16.2 hours in neonates younger than 1 week; 0.77 ml/min/kg, 0.48 L/kg, and 9.2 hours in neonates older than 1 week; and 1.03 ml/min/kg, 0.39 L/kg, and 7.1 hours in older infants, respectively. There was a significant difference in ClT and t 1/2 between the neonates younger and both neonates older than 1 week, and infants. The Vdss was not significantly different among the three age groups. The average renal clearance in neonates younger than 1 week (0.28 ml/min/kg was 70%, in neonates older than 1 week (0.54 ml/min/kg) was 77%, and in older infants (0.49 ml/min/kg) was 47% of ClT, indicating that nonrenal elimination was less developed in neonates. The quantitation of CSF diffusion of ceftriaxone was assessed by comparison of the areas under the CSF and plasma concentration-time curve. The mean ceftriaxone penetration into the CSF in neonates and infants with bacterial meningitis was 17%. On the other hand, penetration in patients with aseptic meningitis amounted to only 4%. Mean ceftriaxone concentrations in the CSF in patients with bacterial meningitis were 2.8 mg/L after 24 hours, exceeding by many times the minimum inhibitory concentration of the common meningitis pathogens at this time.