DISPOSITION AND ELIMINATION OF MEROPENEM IN CEREBROSPINAL-FLUID OF HYDROCEPHALIC PATIENTS WITH EXTERNAL VENTRICULOSTOMY

The broad antibacterial spectrum and the low incidence of seizures in meropenem-treated patients qualifies meropenem for therapy of bacteria l meningitis. The present study evaluates concentrations in ventricula r cerebrospinal fluid (CSF) in the absence of pronounced meningeal inf lammation. Patients with occlusive hydrocephalus caused by cerebrovasc ular diseases, who had undergone external ventriculostomy (n = 10, age range 48 to 75 years), received 2 g of meropenem intravenously over 3 0 min. Serum and CSF were drawn repeatedly and analyzed by liquid chro matography-mass spectroscopy. Pharmacokinetics were determined by nonc ompartmental analysis. Maximum concentrations in serum were 84.7 +/- 2 3.7 mu g/ml. A CSF maximum (C-maxCSF) of 0.63 +/- 0.50 mu g/ml (mean /- standard deviation) was observed 4.1 +/- 2.6 h after the end of the infusion. C-maxCSF and the area under the curve for CSF (AUC(CSF)) de pended on the AUC for serum (AUC(S)), the CSF-to-serum albumin ratio, and the CSF leukocyte count. Elimination from CSF was considerably slo wer than from serum (half-life at beta phase [t(1/2 beta)] of 7.36 +/- 2.89 h in CSF versus t(1/2 beta) of 1.69 +/- 0.60 h in serum). The AU C(CSF)/AUC(S) ratio for meropenem, as a measure of overall CSF penetra tion, was 0.047 +/- 0.022, The AUC(CSF)/AUC(S) ratio for meropenem was similar to that for other p-lactam antibiotics with a low binding to serum proteins. The concentration maxima of meropenem in ventricular C SF observed in this study are high enough to kill fully susceptible pa thogens. They may not be sufficient to kill bacteria with a reduced se nsitivity to carbapenems, although clinical success has been reported for patients with meningitis caused by penicillin-resistant pneumococc i and Pseudomonas aeruginosa.