Schliamser S E, Broholm K A, Liljedahl A L, Norrby S R
Department of Infectious Diseases, University of Umeå, Sweden.
J Antimicrob Chemother. 1988 Nov;22(5):687-95. doi: 10.1093/jac/22.5.687.
Rabbits were given benzylpenicillin, imipenem/cilastatin and a penem beta-lactam, FCE 22101, as constant intravenous infusions with intervals of greater than or equal to 7 days between doses. Neurotoxicity was defined as epileptogenic electroencephalographic (EEG) activity. Mean doses precipitating neurotoxicity were 486 mg/kg of benzylpenicillin, 86 mg/kg of imipenem and 102 mg/kg of FCE 22101 leading to mean serum concentrations of 606, 55 and 30 mg/l, respectively. Doses and serum concentrations of benzylpenicillin were significantly (P less than 0.001) higher than those of imipenem or FCE 22101. Neurotoxicity was seen at significantly (P less than 0.02) higher serum concentrations of imipenem than of FCE 22101. Neurotoxicity seemed to be related to antibiotic concentrations in brain tissue fluid (BTF) rather than to CSF concentrations which were less than 0.2 mg/l in 10 of 11 animals tested after administration of imipenem or FCE 22101. In BTF, significantly (P less than 0.001) higher concentrations of benzylpenicillin than of imipenem or FCE 22101 were found. When related to concurrent serum concentrations, BTF penetration of benzylpenicillin and FCE 22101 did not differ significantly but both these antibiotics penetrated significantly better than imipenem. In conclusion, imipenem/cilastatin and FCE 22101 were more neurotoxic in rabbits than benzylpenicillin but did not show major differences from each other.
给兔子持续静脉输注苄青霉素、亚胺培南/西司他丁和一种青霉烯类β-内酰胺类药物FCE 22101，给药间隔大于或等于7天。神经毒性定义为致癫痫性脑电图（EEG）活动。引发神经毒性的平均剂量分别为苄青霉素486 mg/kg、亚胺培南86 mg/kg和FCE 22101 102 mg/kg，导致的平均血清浓度分别为606、55和30 mg/L。苄青霉素的剂量和血清浓度显著高于亚胺培南或FCE 22101（P<0.001）。亚胺培南引发神经毒性时的血清浓度显著高于FCE 22101（P<0.02）。神经毒性似乎与脑组织液（BTF）中的抗生素浓度有关，而与脑脊液浓度无关，在给予亚胺培南或FCE 22101后，11只受试动物中有10只的脑脊液浓度低于0.2 mg/L。在BTF中，发现苄青霉素的浓度显著高于亚胺培南或FCE 22101（P<0.001）。与同时期的血清浓度相关时，苄青霉素和FCE 22101在BTF中的渗透率没有显著差异，但这两种抗生素的渗透率均显著高于亚胺培南。总之，亚胺培南/西司他丁和FCE 22101在兔子中比苄青霉素更具神经毒性，但彼此之间没有显著差异。
