Ceftriaxone Kinetics and Cerebrospinal Fluid Penetration in Infants and Children with Meningitis

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) μg/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/l2 h. Serum and cerebrospinal fluid concentrations ranged from 120 to 144 and 2.3–4.9 μg/ml at 1.8–5.5 h after the first maintenance dose in 2 patients; 74–139 and 5.7–7.9 μg/ml at 1.3–5.8 h after the second dose in 3 patients and was 101 and 4.1 μg/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 μg/ml, respectively. After the loading and maintenance dose at steady-state, total body clearance averaged 1.17 and 0.64ml/min (p = 0.01); apparent volume of distribution averaged 0.37 and 0.261/kg (p > 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; (2) ceftriaxone kinetics may vary among infants and children with meningitis, and (3) the higher clearance of ceftriaxone noted at the higher dose may be partly due to its concentration-dependent plasma protein binding.

Clinical Pharmacokinetics of Ceftriaxone

“…This property is, in fact, consistent with its minimal affinity for the renal tubular secretory system, which results in CLR close to glomerular filtration rate. After a loading dose of 75 mg/kg given in 15 paediatric patients, 3 to 25% of the serum concentration was measurable in concurrent CSF (1.1 to 8 mg/L) [Nahata et al 1986]. With an 80 mg/kg once-daily regimen in 22 paediatric patients, the CSF level 24 hours after the dose averaged 0.64 to 1.4 mg/L, justifying the use of ceftriaxone for the treatment of meningitis even with once-daily dosing (Dankner et al 1988).…”

Ensuring Safe and Effective Medication Use in Pediatric Patients

“…We documented adequate cerebrospinal fluid concentrations of ceftriaxone, which replaced chloramphenicol for the treatment of bacterial meningitis. 12 Azithromycin was the first antibiotic that could be given once daily for only 5 days to treat certain infections in adults. We did pivotal studies to characterize its pharmacokinetics, documenting adequate concentrations in children with respiratory tract infections.…”

Successful Treatment of Neonatal Citrobacter Freundii Meningitis with Ceftriaxone

“…Ceftriaxone has a long half-life in infants and children (approximately six hours) and it achieves high serum and CSF concentrations. [27][28][29][30] In one study, concentrations as high as 8 ug/ml, were seen in CSF after a 75 mg/kg dose." Ceftriaxone not only penetrates into the central nervous system at concentrations above the MIC for most gram-negative organisms but, once present in the CSF, the concentrations are maintained for prolonged periods of time.…”