Wen Min-Jie, Sung Chih-Chien, Chau Tom, Lin Shih-Hua
Clin Nephrol. 2013 Dec;80(6):474-8. doi: 10.5414/CN107247.
Ertapenem, a novel carbapenem with long-acting antimicrobial activity, is predominantly eliminated by the kidneys. Acute prolonged neurotoxicity associated with recommended doses of ertapenem in patients with advanced renal failure not yet on dialysis has not been reported. Two patients with Stage 5 chronic kidney disease (CKD) developed progressive hallucinations, asterixis, myoclonic jerks, and cognitive impairment after receiving the recommended dose reduction for CKD of ertapenem (500 mg/d) for 4 days (Case 1: acute cholecystitis) and 5 days (Case 2: arteriovenous fistula infection). Exhaustive diagnostic workups were non-revealing. Plasma ertapenem level measured 24 h after the last dose in Patient 2 was 53.7 mg/l, much higher than the therapeutic MIC90 (2 mg/l). Despite the cessation of ertapenem and initiation of high-flux hemodialysis, their neurologic manifestations lasted for 2 weeks. The structural and pharmacokinetic characteristics of ertapenem such as its high lipophilicity, central nervous penetration, and volume of distribution contributed to sustained neurotoxicity even with significant reduction in plasma ertapenem levels by high-flux hemodialysis. Although ertapenem 500 mg/d has been recommended in patients with glomerular filtration rate less than 30 ml/min/1.73 m2, our 2 cases highlight that this dosage might be excessive for patients with Stage 5 CKD, especially those not yet on dialysis.
厄他培南是一种具有长效抗菌活性的新型碳青霉烯类药物，主要经肾脏清除。尚未有报告称，晚期肾衰竭且未接受透析治疗的患者在使用推荐剂量的厄他培南时会出现急性长期神经毒性。两名5期慢性肾脏病（CKD）患者，在接受针对CKD的厄他培南推荐剂量减少量（500mg/d）治疗4天（病例1：急性胆囊炎）和5天（病例2：动静脉瘘感染）后，出现了进行性幻觉、扑翼样震颤、肌阵挛性抽搐和认知障碍。详尽的诊断检查均未发现异常。病例2患者在最后一剂用药24小时后测得的血浆厄他培南水平为53.7mg/L，远高于治疗性MIC90（2mg/L）。尽管停用了厄他培南并开始进行高通量血液透析，但其神经学表现仍持续了2周。厄他培南的结构和药代动力学特征，如高亲脂性、中枢神经系统穿透力和分布容积，导致即使通过高通量血液透析使血浆厄他培南水平显著降低，神经毒性仍持续存在。尽管对于肾小球滤过率低于30ml/min/1.73m²的患者推荐使用每日500mg的厄他培南，但我们的这2例病例表明，对于5期CKD患者，尤其是尚未接受透析治疗的患者，该剂量可能过高。
