title: Cerebrospinal fluid penetration of meropenem in neurocritical care patients with proven or suspected ventriculitis: a prospective observational study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacy, University Hospital of Munich, Marchioninistrasse 15, Munich, 81377, Germany. ute.blassmann@med.uni-muenchen.de.
authors: Ute
authors: http://orcid.org/0000-0002-4288-1745
authors: U
authors: Blassmann
authors: Department of Pharmacy, Heidenheim General Hospital, Schlosshausstrasse 100, Heidenheim, 89522, Germany.
authors: Anka C
authors: AC
authors: Roehr
authors: Department of Pharmacy, Heidenheim General Hospital, Schlosshausstrasse 100, Heidenheim, 89522, Germany.
authors: Otto R
authors: OR
authors: Frey
authors: Department of Pharmacy, University Hospital of Munich, Marchioninistrasse 15, Munich, 81377, Germany.
authors: Cornelia
authors: C
authors: Vetter-Kerkhoff
authors: Department of Neurosurgery, University Hospital of Munich, Marchioninistrasse 15, Munich, 81377, Germany.
authors: Niklas
authors: N
authors: Thon
authors: Department of Molecular and Clinical Pharmacology, University of Liverpool, Sherrington Building, Liverpool, L69 3GE, UK.
authors: William
authors: W
authors: Hope
authors: Department of Anaesthesiology, University Hospital of Munich, Marchioninistrasse 15, Munich, 81377, Germany.
authors: Josef
authors: J
authors: Briegel
authors: Department of Anaesthesiology, University Hospital of Munich, Marchioninistrasse 15, Munich, 81377, Germany.
authors: Volker
authors: V
authors: Huge
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000134:cerebrospinal fluid*; D058565:Cerebral Ventriculitis / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D003422:Critical Care / Q000379:methods*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage / Q000134:cerebrospinal fluid*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: Cerebrospinal fluid; Meropenem; Neurocritical care patients; Pharmacokinetics; Ventriculitis