In difficult to treat infections such as nosocomial ventriculitis, meropenem exposure in the infected compartment is often uncertain but crucial for antibacterial effects. The aim of this study was to investigate the cerebrospinal fluid (CSF) penetration of meropenem in patients with nosocomial ventriculitis and to derive a nomograph to predict effective meropenem doses as a function of clinical parameters.
Retrospective patient data including meropenem serum and CSF levels, as well as CSF inflammation markers were analysed using NONMEM® to assess the general pharmacokinetics and CSF penetration. Monte Carlo simulations (MCS) were used to evaluate different meropenem dosing regimens. Probability of target attainment (PTA) in CSF was assessed and a nomograph to achieve a target concentration of 4 mg/L was developed.
A one-compartment model with meropenem clearance dependent on the estimated glomerular filtration rate (CKD-EPI eGFR, p< 5 e-10) best described meropenem serum pharmacokinetics of 51 critically ill patients. CSF penetration ratio was correlated with the amount of protein in CSF (p 50 ml/min/1.73 m) as well as low CSF protein levels () for a meropenem dose of 6 g/24 h.
High interindividual variability in meropenem CSF concentration was observed in patients with nosocomial ventriculitis. A nomograph to predict the daily meropenem dose required for target attainment for a given eGFR and CSF protein count was developed.

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