Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: a prospective observational study

Blassmann, Ute, Roehr, Anka C, Frey, Otto R, Vetter-Kerkhoff, Cornelia, Thon, Niklas, Hope, William ORCID: 0000-0001-6187-878X, Briegel, Josef and Huge, Volker (2016) Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: a prospective observational study. CRITICAL CARE, 20 (1). 343-.

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Abstract

<h4>Background</h4>Ventriculitis is a complication of temporary intraventricular drains. The limited penetration of meropenem into the cerebrospinal fluid (CSF) is well known. However, ventricular CSF pharmacokinetic data in patients with ventriculitis are lacking. The aim of this study was to evaluate meropenem pharmacokinetics in the serum and CSF of neurocritical care patients with proven or suspected ventriculitis.<h4>Methods</h4>We conducted an observational pharmacokinetic study of neurocritical care patients with proven or suspected ventriculitis receiving meropenem. Multiple blood and CSF samples were taken and were described using nonparametric pharmacokinetic modelling with Pmetrics.<h4>Results</h4>In total, 21 patients (median age 52 years, median weight 76 kg) were included. The median (range) of peak and trough concentrations in serum were 20.16 (4.40-69.00) mg/L and 2.54 (0.00-31.40) mg/L, respectively. The corresponding peak and trough concentrations in CSF were 1.20 (0.00-6.20) mg/L and 1.28 (0.00-4.10) mg/L, respectively, with a median CSF/serum ratio (range) of 0.09 (0.03-0.16). Median creatinine clearance ranged from 60.7 to 217.6 ml/minute (median 122.5 ml/minute). A three-compartment linear population pharmacokinetic model was most appropriate. No covariate relationships could be supported for any of the model parameters. Meropenem demonstrated poor penetration into CSF, with a median CSF/serum ratio of 9 % and high interindividual pharmacokinetic variability.<h4>Conclusions</h4>Administration of higher-than-standard doses of meropenem and therapeutic drug monitoring in both serum and CSF should be considered to individualise meropenem dosing in neurocritical care patients with ventriculitis.

Item Type:	Article
Uncontrolled Keywords:	Meropenem, Cerebrospinal fluid, Pharmacokinetics, Ventriculitis, Neurocritical care patients
Depositing User:	Symplectic Admin
Date Deposited:	23 Mar 2017 07:59
Last Modified:	19 Jan 2023 07:09
DOI:	10.1186/s13054-016-1523-y
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3006564