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Single-dose ceftriaxone pharmacokinetics in pediatric patients with central nervous system infections
Insights
Ceftriaxone demonstrates high efficacy in treating pediatric central nervous system infections. This antibiotic effectively penetrates the cerebrospinal fluid (CSF), exceeding bacterial minimum inhibitory concentrations significantly.
Area of Science:
- Pharmacology
- Infectious Diseases
- Pediatrics
Background:
- Ceftriaxone is a third-generation cephalosporin with broad-spectrum activity.
- Its efficacy in pediatric central nervous system (CNS) infections requires further pharmacokinetic evaluation.
Purpose of the Study:
- To investigate the pharmacokinetics of single-dose ceftriaxone in pediatric patients with CNS infections.
- To determine ceftriaxone penetration into cerebrospinal fluid (CSF) and its relationship with clinical parameters.
Main Methods:
- A pharmacokinetic study involving 17 pediatric patients (0.6-52 months) with CNS infections.
- Randomized intravenous administration of 50 or 75 mg/kg ceftriaxone.
- Serial blood and CSF sampling for drug concentration analysis using high-power liquid chromatography.
Main Results:
- Mean peak plasma concentrations were 184 and 267 microgram/ml for 50 and 75 mg/kg doses, respectively.
- The harmonic mean elimination half-life was 4.2 hours.
- Mean CSF penetration was 4.8%, inversely correlated with CSF glucose concentration.
- CSF ceftriaxone concentrations were significantly higher (480-5,600 times) than minimal inhibitory concentrations.
Conclusions:
- Single-dose ceftriaxone exhibits favorable pharmacokinetics in pediatric CNS infections.
- Adequate CSF penetration and high concentrations support its use in treating serious pediatric infections like meningitis.
Abstract:
Ceftriaxone has greater in vitro and in vivo efficacy against many common bacteria than other third-generation cephalosporins. Single-dose ceftriaxone pharmacokinetics were studied in 17 patients, aged 0.6 to 52 months, with infections of the central nervous system. Patients received a randomized dose of 50 or 75 mg/kg ceftriaxone intravenously over 5 minutes on the second to fifth day of illness. Serial blood samples were collected over 24 hours in all patients, and cerebrospinal fluid (CSF) was obtained 1 to 4.5 hours after injection. Ceftriaxone mean peak plasma concentrations, determined by high-power liquid chromatography, were 267 and 184 microgram/ml for the 75 and 50 mg/kg dosage groups, respectively. The harmonic mean elimination half-life was 4.2 hours, and the mean percent drug penetrance into CSF was 4.8 +/- 3.5%. Of CSF studies evaluated, the glucose concentration was correlated most closely (inversely) with CSF penetration of ceftriaxone. Individual CSF concentrations of ceftriaxone exceeded the minimal inhibitory concentrations of the respective bacteria causing infection by 480 to 5,600 times. Ceftriaxone may be useful in the treatment of serious pediatric infections, including meningitis.