Neurotoxicity of benzylpenicillin in experimental renal failure and Enterobacter cloacae meningitis

The neurotoxic potential of benzylpenicillin administered as a continuous intravenous infusion was studied in rabbits with intact blood-CNS barriers, experimentally established Enterobacter cloacae meningitis and experimental renal failure, secondary to cephaloridine-induced acute tubular necrosis after iv administration. The concentrations of benzylpenicillin in serum, CSF and brain tissue fluid were assayed at the onset of epileptogenic electroencephalographic activity. The brain tissue concentrations of benzylpenicillin were consistently higher than those in CSF in both infected and uninfected animals. The highest brain tissue fluid concentrations of benzylpenicillin were found in rabbits with renal failure after cephaloridine pretreatment. The brain tissue fluid concentrations of benzylpenicillin rather than the CSF concentrations were decisive for neurotoxicity. Cephaloridine-induced uraemia, but not the combination of uraemia and meningitis, resulted in a significantly increased tolerance of high intracerebral concentrations of benzylpenicillin before EEG-changes were precipitated.