碳青霉烯类抗生素的神经毒性

Neurotoxicity of carbapenem antibiotics

碳青霉烯类是一类具有广谱抗菌作用的β-内酰胺类抗生素。其常用药物包括亚胺培南、美罗培南、厄他培南、法罗培南、帕尼培南和多尼培南等。此类药物可诱发神经毒性,发生率约为0.01%～3%。神经毒性主要临床表现为头痛、惊厥、癫痫、肌阵挛、意识障碍等。神经毒性的发生机制为碳青霉烯类抗生素阻止γ-氨基丁酸(γ-GABA)与受体的结合,从而干扰γ-GABA的神经抑制作用,导致癫痫等神经毒性发生。神经毒性反应的危险因素包括患者肾功能减退、中枢神经系统病变、合并用药等。防治措施:根据不同种类碳青霉烯类抗生素与癫痫的相关性合理选择药物;应谨慎调整肾衰竭患者的使用剂量;避免与高剂量茶碱、非甾体抗炎药及丙磺舒等合用;儿童及老年患者用药过程中应进行监测;一旦出现癫痫发作应立即停药,必要时可选用地西泮或丙戊酸钠治疗;癫痫无法控制者可用血液透析治疗。

Carbapenems are a class of β-lactam antibiotics with a broad spectum of antibacterial activity. The commonly used carbapenems are imipenem,meropenem,ertapenem,faropenem,panipenem,doripenem,and so on. Carbapenem antibiotics could induce neurotoxicity and the incidence is about 0. 01% -0. 3% . The main clinical manifestations of neurotoxicity are headache, convulsions,seizures,myoclonus,and disorder of consciousness. The mechanism of neurotoxicity induced by carbapenem antibiotics is thought to be related to inhibition of the γ-aminobutyric acid （ γ-GABA） binding to the receptors and interruption neural inhibitory effect of γ-GABA eventally resulting in seizures and other neurological disorders. The risk factors for neurotoxic reactions include decreased renal function,pathologic changes in CNS,and combination therapy. The prevention and treatment of neurotoxicity induced by carbapenems are as follows： it is essential to consider appropriate choice of carbapenem antibiotics according to the relationship between seizures and the different types of the antibiotics; dosage should be carefully adjusted in patients with renal failure; concomitant use with other drugs such as high-dose theophylline,NSAIDs,probenecid,and so on should be avoided; the children and elderly patients should be monitored during treatment; if carbapenem-induced seizures occur,the agent should be stopped and diazepam or sodium valproate may be given if necessary; hemodialysis could be used for patients with uncontrolled seizures induced by the antibiotics.