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Pharmacokinetics and cerebrospinal fluid (CSF) concentrations of vancomycin in pediatric patients undergoing CSF
P Fan-Havard1, M C Nahata, M H Bartkowski
1College of Pharmacy, Ohio State University, Columbus.
Abstract:
Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 +/- 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 micrograms/ml; cerebrospinal fluid concentrations ranged from less than 0.6 to 0.8 microgram/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 +/- 0.05 l/h/kg, 0.07 +/- 0.02 l/h/kg, 0.54 +/- 0.15 l/kg, and 4.8 +/- 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Vancomycin prophylaxis for pediatric cerebrospinal fluid shunt infections showed low cerebrospinal fluid concentrations intraoperatively. Further research is needed to optimize dosing for effective treatment against methicillin-resistant Staphylococcus epidermidis.
Area of Science:
- Neurosurgery
- Infectious Diseases
- Pharmacokinetics
Background:
- Staphylococcus epidermidis is a common cause of cerebrospinal fluid shunt infections.
- Clinical isolates are often methicillin-resistant.
- Vancomycin is a common prophylactic antibiotic for neurosurgery.
Purpose of the Study:
- To characterize vancomycin pharmacokinetics in pediatric patients undergoing cerebrospinal fluid shunt surgery.
- To determine intraoperative cerebrospinal fluid concentrations of vancomycin.
Main Methods:
- Eight pediatric patients received vancomycin (15 mg/kg every 6 h).
- Blood, cerebrospinal fluid, and urine samples were collected.
- Vancomycin levels were measured using fluorescence polarization immunoassay.
Main Results:
- Peak serum concentrations ranged from 15.6 to 33.7 µg/ml.
- Cerebrospinal fluid concentrations were low, ranging from <0.6 to 0.8 µg/ml.
- Mean total clearance was 0.11 L/h/kg, with significant inter-patient variability.
Conclusions:
- Intraoperative vancomycin dosing resulted in low cerebrospinal fluid concentrations in pediatric patients.
- Pharmacokinetic variability was observed.
- Current dosing may not achieve therapeutic cerebrospinal fluid levels for shunt infections.