Microdialysis study of meropenem cerebral distribution in patients with acute brain injury
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KeywordsMeropenem Cerebral Spinal Fluid Acute Brain Injury Unbind Concentration Probe Recovery
Antibiotic dosing recommendations are usually based on plasma or cerebral spinal fluid pharmacokinetic (PK) studies. However, as infections mainly occur in extracellular tissue fluid (ECF), corresponding unbound ECF antibiotic concentrations are responsible for the antimicrobial effect. Because of the blood-brain barrier, the cerebral antibiotic distribution is thought to be reduced compared with tissues without any physiological barrier. This study aims to determine meropenem (MPM) unbound concentrations in the brain and compare them with MPM concentrations in plasma to explore cerebral distribution of MPM in patients with acute brain injury.
After local ethic approval and written informed consent, two brain-injured patients, sedated, mechanically ventilated, receiving MPM for an infection and monitored by cerebral microdialysis (CMA 71, membrane length 10 mm, membrane diameter 0.6 mm, molecular cut-off 100 kDa; CMA, Stockholm, Sweden) were enrolled. The PK study succeeded to 1 g meropenem over 30 minutes and brain dialysates and blood samples were collected over 420 minutes. Probe recoveries were evaluated individually by retrodialysis. MPM was assayed by HPLC coupled with tandem mass spectrometry (LC-MS/MS).
The MPM brain AUC is much lower than plasma AUC for the two patients enrolled, consistent with the PK theory in the presence of tissue with efflux transporters. More patients are needed to better understand MPM brain distribution characteristics.