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泊沙康唑静脉给药治疗肝肾功能损害患者侵袭性土曲霉感染的病例报告:治疗药物监测的安全性及作用

A case report of intravenous posaconazole in hepatic and renal impairment patient with invasive Aspergillus terreus infection: safety and role of therapeutic drug monitoring.

作者信息

Dilokpattanamongkol Pitchaya, Panusitthikorn Panadda, Boonprasert Rasda, Chayakulkeeree Methee, Rotjanapan Porpon

机构信息

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya Road, Ratchathewi, Bangkok, 10400, Thailand.

Department of Pharmacy, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wanglang Road Bangkoknoi, Bangkok, 10700, Thailand.

出版信息

BMC Pharmacol Toxicol. 2017 Jan 31;18(1):8. doi: 10.1186/s40360-017-0115-z.

Abstract

BACKGROUND

Invasive aspergillosis (IA) is a fatal infectious complication among immunocompromised patients. Aspergillus terreus, the fourth common species can be difficult to treat due to a unique resistance pattern. To date, there has been no report on safety and dose adjustment when intravenous posaconazole is selected in hepatic and renal impairment patient. We present a rare case of intravenous posaconazole use in a hepatic and renal impairment patient with invasive A. terreus pulmonary infection. To our knowledge, this is the first report of intravenous posaconazole use in IA due to A. terreus with hepatic and renal impairment focusing on drug safety and role of therapeutic drug monitoring (TDM).

CASE PRESENTATION

A 37-year-old previously healthy man with diagnosis of dengue hemorrhagic fever and shock complicated with hepatic and renal impairment proposed to have proven invasive A. terreus pulmonary infection is described. Due to lack of good clinical response and concern of potential adverse effects whilst on intravenous voriconazole, intravenous posaconazole 300 mg every 48 h was chosen with confirmed therapeutic plasma concentrations. Despite the death of the patient and IA deemed uncontrollable, there were no significant side effects attributable to intravenous posaconazole use demonstrated over a period of 34 days.

CONCLUSIONS

Intravenous posaconazole use with TDM implementation maybe a safe alternative option to standard therapy. Therapeutic plasma posaconazole level may be reached at lower dosing regimen in renal and hepatic impairment patient. However, explanations of clinical failure on this patient with immunodeficiency state were multifactorial.

摘要

背景

侵袭性曲霉病(IA)是免疫功能低下患者中一种致命的感染性并发症。土曲霉是第四常见的菌种,由于其独特的耐药模式,可能难以治疗。迄今为止,尚无关于肝肾功能损害患者选用静脉注射泊沙康唑时的安全性及剂量调整的报道。我们报告了1例肝肾功能损害患者静脉注射泊沙康唑治疗侵袭性土曲霉肺部感染的罕见病例。据我们所知,这是首例关于肝肾功能损害患者因土曲霉导致IA而使用静脉注射泊沙康唑并重点关注药物安全性及治疗药物监测(TDM)作用的报道。

病例介绍

描述了1例37岁既往健康男性,诊断为登革出血热并休克,并发肝肾功能损害,确诊为侵袭性土曲霉肺部感染。由于静脉注射伏立康唑时缺乏良好的临床反应且担心潜在不良反应,选择每48小时静脉注射300mg泊沙康唑,并确认达到治疗性血浆浓度。尽管患者死亡且IA被认为无法控制,但在34天的时间里,未显示出静脉注射泊沙康唑有明显副作用。

结论

静脉注射泊沙康唑并实施TDM可能是标准治疗的一种安全替代选择。在肝肾功能损害患者中,较低的给药方案可能达到泊沙康唑治疗性血浆水平。然而,该免疫缺陷状态患者临床治疗失败的原因是多方面的。

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