The Pharmacokinetics and Pharmacodynamics of Meropenem in the Cerebrospinal Fluid of Neurosurgical Patients

Abstract

This study examined the pharmacokinetics and pharmacodynamics of meropenem in cerebrospinal fluid (CSF). Meropenem (0.5 g every 8 h) was administered by 0.5-h infusion to six neurosurgical patients. Lumbar CSF and venous blood samples were obtained at 0.5-16 h after the start of the first infusion. Drug concentrations in the CSF and plasma were analyzed pharmacokinetically and used for a Monte Carlo simulation with the minimum inhibitory concentration (MIC) data of clinical isolates in Japan. Meropenem penetrated into the CSF with the area under the drug concentration-time curve ratio of 0.10 ± 0.03 (mean ± SD) and the repeated infusions caused the drug concentration in the CSF to accumulate slightly. Against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli isolates, 0.5 g q8h achieved a >90% probability of pharmacodynamic target (50% of the time above MIC) attainment, and 1 g q8h was needed for a >90% probability of target (100% of the time above MIC) attainment. However, against Pseudomonas aeruginosa, 2 g q8h achieved a lower probability of target attainment. These results should help us to better elucidate the pharmacokinetics of meropenem in the cerebrospinal space while also helping us to choose the appropriate drug dosages for the management of bacterial meningitis.

Keywords:

• Population pharmacokinetics
• Monte Carlo simulation
• probability of target attainment