Model-informed identification of optimised dosing strategies for meropenem in critically ill patients receiving SLEDD: an observational study.

IF 3.6 2区医学 Q1 INFECTIOUS DISEASES

Infection Pub Date : 2025-10-01 Epub Date: 2025-04-25 DOI:10.1007/s15010-025-02504-0

Franz Weber, Christina Scharf, Linda B S Aulin, Ferdinand Weinelt, Michael Paal, Gerd Mikus, Michael Vogeser, Katharina Habler, Wilhelm Huisinga, Michael Zoller, Robin Michelet, Charlotte Kloft, Uwe Liebchen

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引用次数: 0

Abstract

Purpose: An increasing number of critically ill patients receive slow extended daily dialysis (SLEDD) due to their pathophysiology while suffering from sepsis, necessitating effective and safe antibiotic therapy. Although SLEDD reduces meropenem exposure and increases treatment failure risk, effective and safe dosing regimens are unclear. We aimed to identify optimised meropenem dosing strategies for critically ill SLEDD patients through population pharmacokinetic (PK) modelling and PK/pharmacodynamic (PD)-based probability of target attainment (PTA) analysis.

Methods: Clinical data from a prospective study involving critically ill SLEDD patients receiving meropenem were monitored through routine therapeutic drug monitoring. A total of 178 blood samples from 13 patients (median 14 samples per patient) were analysed. A PK model was developed and utilised to evaluate 24 clinically relevant dosing regimens during SLEDD therapy (7-h on-SLEDD periods q24h) in PTA analyses. The PK/PD target window of minimum meropenem concentration between 8 mg/L (P. aeruginosa; R-breakpoint) and 44.45 mg/L (toxicity threshold) was used.

Results: A one-compartment PK model with linear elimination and total clearance (CL) split into renal (CL_REN; 45%) and SLEDD-associated (55%) CL well characterised the SLEDD data. Creatinine clearance (urine-collected; CLCR_urine) was identified as significant factor on CL_REN. Continuous infusions, specifically 2 g q24h for CLCR_urine 0-25 mL/min and 3 g q24h for CLCR_urine 25-40 mL/min, showed the highest PTA being effective and safe during SLEDD therapy. A comprehensive dosing nomogram was developed.

Conclusion: Our easy-to-use dosing nomogram presents a promising tool in optimising meropenem dosing regimens for critically ill SLEDD patients considering their kidney function in clinical practice.

Trial registration: Clinicaltrials.gov NCT03985605. Registered 14 June 2019. https://classic.

Clinicaltrials: gov/ct2/show/study/NCT03985605.

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在接受SLEDD的危重患者中，基于模型的美罗培南最佳给药策略识别：一项观察性研究。

目的：越来越多的危重患者在脓毒症的病理生理条件下需要缓慢延长每日透析（SLEDD），需要有效安全的抗生素治疗。尽管SLEDD减少了美罗培南暴露并增加了治疗失败的风险，但有效和安全的给药方案尚不清楚。我们旨在通过群体药代动力学（PK）模型和基于PK/药效学（PD）的目标实现概率（PTA）分析，确定危重期SLEDD患者的最佳美罗培南剂量策略。方法：通过常规治疗药物监测，对接受美罗培南治疗的危重SLEDD患者的临床资料进行前瞻性研究。共分析了13例患者的178份血样（平均每位患者14份血样）。在PTA分析中，建立了一个PK模型，并用于评估SLEDD治疗期间24种临床相关给药方案（7小时非SLEDD期间q24小时）。最小美罗培南浓度在8 mg/L (P. aeruginosa；r -断点)和44.45 mg/L（毒性阈值）。结果：线性消除和总清除率（CL）的单室PK模型分为肾（CLREN）；45%)和SLEDD相关的CL（55%）很好地表征了SLEDD数据。肌酐清除率(收集尿液；clcr尿)是影响CLREN的显著因素。连续输注，特别是clcr尿0- 25ml /min 2 g q24h和clcr尿25- 40ml /min 3 g q24h，在SLEDD治疗期间显示最高PTA是有效和安全的。研制了一种综合给药谱图。结论：我们易于使用的给药图为临床实践中考虑肾功能的危重SLEDD患者优化美罗培南给药方案提供了一个有希望的工具。试验注册：Clinicaltrials.gov NCT03985605。2019年6月14日注册。https://classic.Clinicaltrials: gov / ct2 /显示/研究/ NCT03985605。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection 医学-传染病学

CiteScore

12.50

自引率

1.30%

发文量

224

审稿时长

6-12 weeks

期刊介绍： Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings. The journal covers a wide range of topics, including: Etiology: The study of the causes of infectious diseases. Pathogenesis: The process by which an infectious agent causes disease. Diagnosis: The methods and techniques used to identify infectious diseases. Treatment: The medical interventions and strategies employed to treat infectious diseases. Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies. Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections. In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.