Schliamser S E, Bolander H, Broholm K A, Gerdes U, Kourtopoulos H, Norrby S R
Department of Infectious Diseases, University of Umeå, Sweden.
J Antimicrob Chemother. 1989 Aug;24(2):215-25. doi: 10.1093/jac/24.2.215.
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.
在具有完整血脑屏障的兔子、实验性建立的阴沟肠杆菌脑膜炎模型以及静脉注射头孢菌素诱导急性肾小管坏死继发实验性肾衰竭的兔子中，研究了持续静脉输注苄青霉素的神经毒性潜力。在致癫痫性脑电图活动开始时，测定血清、脑脊液和脑组织液中苄青霉素的浓度。在感染和未感染的动物中，脑组织中苄青霉素的浓度始终高于脑脊液中的浓度。在头孢菌素预处理后出现肾衰竭的兔子中，脑组织液中苄青霉素的浓度最高。决定神经毒性的是脑组织液中苄青霉素的浓度，而非脑脊液中的浓度。头孢菌素诱导的尿毒症，而非尿毒症与脑膜炎的联合作用，导致在脑电图改变出现之前，对高脑内浓度苄青霉素的耐受性显著增加。
