INT-001 Serum and cerebrospinal fluid concentrations of meropenem in neurocritical care patients with central nervous system infections

BackgroundMeropenem plus vancomycin is recommended for hospital acquired CNS infections. The limited penetration of meropenem into the CSF is well known. However, data regarding the disposition of meropenem in CSF in these patients are lacking.PurposeThe aim of this study was to describe concentrations of meropenem in serum and CSF in neurocritical care patients with intraventricular drains and hospital acquired CNS infections.Material and methodsThis was an observational study in neurocritical care patients with CNS infections receiving meropenem. Multiple blood and CSF samples were taken and analysed by a validated high performance liquid chromatography assay. The primary pharmacokinetic/pharmacodynamic targets were concentrations above the minimum inhibitory concentration (MIC) of suspected pathogens at 50% (50% T>4xMIC) of the dosing interval in serum and concentrations above the MIC throughout the entire dosing interval (100% T>MIC) in serum and CSF. Variables are described with median values (range).Results9 patients (mean age 57±8 years, mean weight 76±12 kg) were enrolled. A total of 74 serum samples and 70 CSF samples were analysed. The median peak and trough concentrations in serum were 29.00 (10.70–69.00) mg/L and 4.60 (0.00–31.40) mg/L, respectively. The median corresponding peak and trough concentrations in CSF were 1.45 (0.27–6.20) mg/L and 1.35 (0.00–4.10) mg/L, respectively. Assuming an MIC of 2 mg/L, all patients achieved 50% T>4xMIC in serum and 75.7% of all measured dosing intervals achieved 100% T>MIC. In CSF, 42.9% of all concentrations reached 2 mg/L.ConclusionMeropenem demonstrated adequate CSF concentrations for high susceptible pathogens. CSF concentrations for pathogens with reduced susceptibility such as Pseudomonas aeruginosa are not assured. With the high interindividual pharmacokinetic variability observed, therapeutic drug monitoring in serum and CSF should be considered to individualise meropenem dosing in neurocritical care patients with CNS infections.References and/or acknowledgementsThis work was supported within the interprofessional PhD programme Clinical Pharmacy, LMU Munich, Germany.Conflict of interest:Corporate sponsored research or other substantive relationships: This work was supported by Lesmueller Stiftung, Munich, Germany.