Resolution of acyclovir-associated neurotoxicity with the aid of improved clearance estimates using a Bayesian approach: A case report and review of the literature.
Resolution of acyclovir-associated neurotoxicity with the aid of improved clearance estimates using a Bayesian approach: A case report and review of the literature.
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DOI：
10.1111/jcpt.12520
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发表时间：
2017-06
影响因子：
2
通讯作者：
Scheetz MH
中科院分区：
文献类型：
--
作者：
Watson WA;Rhodes NJ;Echenique IA;Angarone MP;Scheetz MH
神经毒性是阿昔洛韦的副作用。据我们所知，我们报告了第一例贝叶斯清除率估计支持无环病毒相关神经毒性治疗干预的病例。一名诊断为播散性带状疱疹的62岁男性在出现急性神经毒性症状时接受静脉注射（IV）阿昔洛韦治疗。根据传统的肌酐清除率估计，阿昔洛韦对肾功能进行了剂量调整；然而，由于患者同时使用万古霉素，因此对万古霉素清除率进行了贝叶斯估计，结果显示肌酐清除率降低了2倍。根据贝叶斯估计，停用了阿昔洛韦，并在24小时内注意到精神状态的改善。除了Cockcroft-Gault之外，其他评估肾功能的方法，如本例患者使用的贝叶斯方法，在人群估计可能不准确且对患者有潜在危险时，应考虑使用。无环鸟苷在水痘、带状疱疹和单纯疱疹病毒感染的治疗和预防方面是非常有效的。阿昔洛韦和伐昔洛韦的积累与神经毒性有关，表现为精神状态恶化，在某些情况下出现幻觉、躁动或嗜睡。大多数描述无环鸟苷相关神经毒性的报告都与受影响患者的肾功能障碍相吻合，因为无环鸟苷主要通过尿液排出。肾功能障碍似乎是无环韦相关神经毒性的一个强有力的预测因素，因为它被认为是神经毒性风险的增强因素。然而，阿昔洛韦相关神经毒性的确切暴露-毒性关系尚未得到很好的定义。
Neurotoxicity is a side effect of acyclovir. We report the first case, to our knowledge, whereby Bayesian-informed clearance estimates supported a therapeutic intervention for acyclovir-associated neurotoxicity. A 62 year-old male with the diagnosis of disseminated zoster was being treated with intravenous (IV) acyclovir when he developed symptoms of acute neurotoxicity. Acyclovir had been dose-adjusted for renal dysfunction according to traditional creatinine clearance estimates; however, since the patient was also on vancomycin, Bayesian estimates of vancomycin clearances were performed, which revealed a 2-fold lower creatinine clearance. In response to the Bayesian estimates, acyclovir was discontinued, and improvements in mentation were noted within 24 hours. Alternate approaches to estimate renal function beyond Cockcroft-Gault, such as a Bayesian approach used in our patient, should be considered when population estimates are both likely to be inaccurate and potentially dangerous to the patient. Acyclovir is highly efficacious in the treatment and prophylaxis of varicella zoster and herpes simplex viral infections. Accumulation of acyclovir and valacyclovir have been associated with neurotoxocity, manifesting as worsening of mental status, in some cases hallucinations, agitation, or lethargy. Most reports that describe acyclovir-associated neurotoxicity coincide with renal dysfunction in the affected patient, as acyclovir is eliminated primarily through excretion in the urine. Renal dysfunction appears to be a strong predictor of acyclovir-associated neurotoxicity as it is thought to potentiate the risk for neurotoxicity. However, the exact exposure-toxicity relationship for acyclovir-associated neurotoxicity has not been well defined.