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Ceftriaxone kinetics and cerebrospinal fluid penetration in infants and children with meningitis
Insights
This study found that ceftriaxone effectively achieves adequate cerebrospinal fluid (CSF) concentrations in pediatric patients with bacterial meningitis. The tested dosage regimen ensures sufficient drug levels for treating this serious infection.
Area of Science:
- Pharmacokinetics
- Infectious Diseases
- Pediatric Pharmacology
Background:
- Bacterial meningitis is a severe infection requiring effective antibiotic treatment.
- Ceftriaxone is a commonly used antibiotic for bacterial meningitis in children.
- Understanding drug concentrations in cerebrospinal fluid (CSF) is crucial for treatment efficacy.
Purpose of the Study:
- To determine serum and CSF concentrations of ceftriaxone in pediatric patients with bacterial meningitis.
- To evaluate the pharmacokinetic profile of ceftriaxone following loading and maintenance doses.
- To assess the adequacy of CSF drug levels with the studied dosage regimen.
Main Methods:
- Studied 20 pediatric patients (0.4-5.6 years) with bacterial meningitis receiving ceftriaxone.
- Measured simultaneous serum and CSF ceftriaxone concentrations using High-Performance Liquid Chromatography (HPLC).
- Analyzed drug concentrations after intravenous loading doses (75 mg/kg) and maintenance doses (50 mg/kg/12h).
- Determined pharmacokinetic parameters including clearance, volume of distribution, and elimination half-life at steady-state.
Main Results:
- CSF ceftriaxone concentrations ranged from 3-25% of simultaneous serum concentrations after loading doses.
- Serum concentrations after maintenance doses varied based on dose timing and number of doses administered.
- Steady-state peak and trough serum concentrations were within therapeutic ranges.
- Total body clearance was significantly different after loading vs. maintenance doses (1.17 vs. 0.64 ml/min, p=0.01).
- Elimination half-life was also significantly different (3.7 vs. 4.6 h, p=0.01).
Conclusions:
- The studied ceftriaxone dosage regimen achieves adequate concentrations in the cerebrospinal fluid of pediatric patients with bacterial meningitis.
- The findings support the use of this regimen for effective treatment of bacterial meningitis in this population.
- Pharmacokinetic parameters suggest dose-dependent changes in clearance and half-life.
Abstract:
20 patients (0.4-5.6 years old) receiving ceftriaxone for the treatment of bacterial meningitis were studied. Simultaneous serum and cerebrospinal fluid concentrations of ceftriaxone were determined by HPLC in 15 patients at 11.4-12.8 h after an intravenous loading dose of 75 mg/kg. Serum and cerebrospinal fluid concentrations ranged from 20.5 to 44.9 (31.3 +/- 7.8) and from 1.1 to 8.0 (3.7 +/- 1.8) micrograms/ml, respectively. Cerebrospinal fluid concentrations ranged from 3 to 25% (12 +/- 6%) of the simultaneous serum concentrations. In 6 patients, serum and cerebrospinal fluid concentrations were determined after maintenance doses of 50 mg/kg/12 h. Serum and cerebrospinal fluid concentrations ranged from 120 to 144 and 2.3-4.9 micrograms/ml at 1.8-5.5 h after the first maintenance dose in 2 patients; 74-139 and 5.7-7.9 micrograms/ml at 1.3-5.8 h after the second dose in 3 patients and was 101 and 4.1 micrograms/ml at 4 h after the 3rd dose in 1 patient. Multiple blood samples were collected after the loading dose in 5 patients and after 9-10 days of maintenance doses in 3 patients. Steady-state peak and trough serum concentrations ranged from 295 to 440 and 32.6-44.8 micrograms/ml, respectively. After the loading and maintenance dose at steady-state, total body clearance averaged 1.17 and 0.64 ml/min (p = 0.01); apparent volume of distribution averaged 0.37 and 0.26 l/kg (p greater than 0.05); and elimination half-life averaged 3.7 and 4.6 h (p = 0.01), respectively. These results suggest that (1) adequate cerebrospinal fluid concentrations of ceftriaxone can be achieved in patients with meningitis with the dosage regimen studied.(ABSTRACT TRUNCATED AT 250 WORDS)