Lee K-H, Ueng Y-F, Wu C-W, Chou Y-C, Ng Y-Y, Yang W-C
Division of Nephrology, Taipei Veterans General Hospital, National Yang Ming University, Taipei, Taiwan.
J Clin Pharm Ther. 2015 Apr;40(2):240-4. doi: 10.1111/jcpt.12239. Epub 2014 Dec 9.
Dosage adjustment of 500 mg ertapenem daily is recommended for patients with advanced kidney disease. 30% of ertapenem is cleared by a session of haemodialysis (HD). However, because most published carbapenems studies have excluded patients on dialysis, little is known about the dosing of ertapenem to avoid central nervous system (CNS) toxicity in regular HD patients. We report of four patients who developed CNS toxicity in such patients.
The 4 HD patients developed unexplained CNS toxicity manifested as seizures, hallucination and cognitive dysfunction after receiving 3-7 consecutive recommended doses of ertapenem. Their symptoms of CNS toxicity were completely resolved within 8 days after discontinuation of ertapenem. In one of our presented cases, we demonstrated the very high level of plasma ertapenem accumulating with several consecutive doses. Cognitive function gradually recovered in line with a corresponding decline in blood level of ertapenem.
This is the first report of ertapenem-associated CNS toxicity in patients on regular HD and utilizing the plasma ertapenem concentration to demonstrate the causal relationship. The recommended dosage of 500 mg ertapenem daily may be still too high in regular HD patients, especially in Asians, owing to their relatively small body size. An increased awareness of ertapenem-associated CNS toxicity would avoid unnecessary examinations, hospitalization, and potentially catastrophic complications.
对于晚期肾病患者，建议每日使用500毫克厄他培南时进行剂量调整。30%的厄他培南可通过一次血液透析（HD）清除。然而，由于大多数已发表的碳青霉烯类药物研究都排除了透析患者，对于维持性血液透析患者中避免中枢神经系统（CNS）毒性的厄他培南给药剂量知之甚少。我们报告了4例此类患者发生中枢神经系统毒性的情况。
4例血液透析患者在连续接受3 - 7剂推荐剂量的厄他培南后，出现了原因不明的中枢神经系统毒性，表现为癫痫发作、幻觉和认知功能障碍。停用厄他培南后8天内，他们的中枢神经系统毒性症状完全消失。在我们展示的一个病例中，我们证明了连续多次给药后血浆厄他培南水平非常高。认知功能随着厄他培南血药浓度相应下降而逐渐恢复。
这是关于维持性血液透析患者中厄他培南相关中枢神经系统毒性的首次报告，并利用血浆厄他培南浓度证明了因果关系。对于维持性血液透析患者，尤其是体型相对较小的亚洲人，每日500毫克厄他培南的推荐剂量可能仍然过高。提高对厄他培南相关中枢神经系统毒性的认识将避免不必要的检查、住院和潜在的灾难性并发症。
