血液透析中心静脉导管的滔罗尼定和肝素导管锁定液

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY American journal of therapeutics Pub Date : 2024-07-01 Epub Date: 2024-05-07 DOI:10.1097/MJT.0000000000001736
Timothy Nguyen, Bernard C Camins, David A Butler
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引用次数: 0

摘要

背景:慢性肾病可导致终末期肾病,而且发病率正在上升。许多开始血液透析的患者需要使用中心静脉导管(CVC)。导管相关血流感染(CRBSI)是一种常见的并发症,可导致严重的发病率和死亡率。预防 CRBSI 的干预措施包括抗菌素锁定疗法,但抗菌素耐药性的产生和不良反应令人担忧。非抗菌消毒剂也被用作导管锁定溶液。滔罗立定和肝素导管锁定溶液首次获得美国食品和药物管理局批准,用于预防血液透析患者的 CRBSI。滔罗立定具有独特的作用机制和良好的安全性:滔罗立定和肝素导管锁溶液具有抗菌和抗凝特性。滔罗立定是氨基酸牛磺酸的衍生物,肝素则来自猪肠粘膜。滔罗匹定不仅能破坏微生物细胞壁,还能阻止微生物附着在生物表面,防止生物膜的形成。滔罗立定和肝素导管锁溶液用于导管内腔,应吸入导管。由于是局部使用,因此药代动力学和药效学数据有限:LOCK-IT-100 试验是一项随机、双盲、三期研究,共纳入了 795 名使用 CVC 进行血液透析的终末期肾病患者。牛磺必利和肝素与单独使用肝素的对照组进行了比较。研究结果显示,滔罗尼定和肝素组的 CRBSI 风险降低了 71%(95% 置信区间:38%-86%,P = 0.0006)。其他研究也表明,滔罗立定锁定溶液可减少 CRBSI 的发生。在成人和儿童人群中使用滔罗尼定的几项系统回顾和荟萃分析也显示,CRBSI 的发生率有所下降:滔罗尼定和肝素锁溶液为通过 CVC 进行血液透析的患者提供了一种新型预防策略,可降低 CRBSI 风险。这是一项重大进展,因为对于导管是唯一救命治疗选择的患者来说,目前还没有其他类似的选择。
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Taurolidine and Heparin as Catheter Lock Solution for Central Venous Catheters in Hemodialysis.

Background: Chronic kidney disease can lead to end-stage renal disease, and the prevalence is increasing. Many patients starting hemodialysis require central venous catheters (CVCs). Catheter-related bloodstream infections (CRBSIs) are a common complication and lead to significant morbidity and mortality. Interventions to prevent CRBSI include antimicrobial lock therapy but concern for the development of antimicrobial resistance and adverse effects. Nonantimicrobial antiseptics as catheter lock solutions have also been used. Taurolidine and heparin catheter lock solution is first approved by the Food and Drug Administration for the prevention of CRBSI in patients on hemodialysis. Taurolidine has a unique mechanism of action and favorable safety profile.

Mechanism of action, pharmacodynamics, and pharmacokinetics: Taurolidine and heparin catheter lock solution have both antimicrobial and anticoagulant properties. Taurolidine is derivative of the amino acid taurine, and heparin is derived from porcine intestinal mucosa. Taurolidine not only damages microbial cell walls but also prevents the adherence of microorganisms to biological surfaces, preventing biofilm formation. Taurolidine and heparin catheter lock solution is intended to be used intraluminally within the catheter and should be aspirated. Because it is used locally, limited pharmacokinetic and pharmacodynamic data are available.

Clinical trials: The LOCK-IT-100 trial is a randomized, double-blind, phase 3 study, which included 795 end-stage renal disease patients on hemodialysis with CVC. Taurolidine and heparin was compared with the control heparin alone. The results of the study showed a 71% risk reduction in CRBSI for taurolidine and heparin arm (95% confident interval, 38%-86%, P = 0.0006). Other studies have also shown that taurolidine lock solution leads to decreased CRBSI episodes. Several systematic reviews and meta-analysis consisted of taurolidine in adult, and pediatric populations also showed reduction in the incidence of CRBSIs.

Therapeutic advance: Taurolidine and heparin lock solution represents a novel preventive strategy for those undergoing hemodialysis through a CVC by reducing the risk of CRBSI. This is significant progress because there are no other similar options available for patients for whom catheters are the only options for their life-saving treatment.

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来源期刊
American journal of therapeutics
American journal of therapeutics PHARMACOLOGY & PHARMACY-
CiteScore
5.50
自引率
9.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: American Journal of Therapeutics is an indispensable resource for all prescribing physicians who want to access pharmacological developments in cardiology, infectious disease, oncology, anesthesiology, nephrology, toxicology, and psychotropics without having to sift through stacks of medical journals. The journal features original articles on the latest therapeutic approaches as well as critical articles on the drug approval process and therapeutic reviews covering pharmacokinetics, regulatory affairs, pediatric clinical pharmacology, hypertension, metabolism, and drug delivery systems.
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