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
{"title":"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。","authors":"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","doi":"10.1007/s15010-025-02504-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>A one-compartment PK model with linear elimination and total clearance (CL) split into renal (CL<sub>REN</sub>; 45%) and SLEDD-associated (55%) CL well characterised the SLEDD data. Creatinine clearance (urine-collected; CLCR<sub>urine</sub>) was identified as significant factor on CL<sub>REN</sub>. Continuous infusions, specifically 2 g q24h for CLCR<sub>urine</sub> 0-25 mL/min and 3 g q24h for CLCR<sub>urine</sub> 25-40 mL/min, showed the highest PTA being effective and safe during SLEDD therapy. A comprehensive dosing nomogram was developed.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT03985605. Registered 14 June 2019. https://classic.</p><p><strong>Clinicaltrials: </strong>gov/ct2/show/study/NCT03985605.</p>","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":"1819-1831"},"PeriodicalIF":3.6000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460387/pdf/","citationCount":"0","resultStr":"{\"title\":\"Model-informed identification of optimised dosing strategies for meropenem in critically ill patients receiving SLEDD: an observational study.\",\"authors\":\"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\",\"doi\":\"10.1007/s15010-025-02504-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>A one-compartment PK model with linear elimination and total clearance (CL) split into renal (CL<sub>REN</sub>; 45%) and SLEDD-associated (55%) CL well characterised the SLEDD data. Creatinine clearance (urine-collected; CLCR<sub>urine</sub>) was identified as significant factor on CL<sub>REN</sub>. Continuous infusions, specifically 2 g q24h for CLCR<sub>urine</sub> 0-25 mL/min and 3 g q24h for CLCR<sub>urine</sub> 25-40 mL/min, showed the highest PTA being effective and safe during SLEDD therapy. A comprehensive dosing nomogram was developed.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT03985605. 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Model-informed identification of optimised dosing strategies for meropenem in critically ill patients receiving SLEDD: an observational study.
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 (CLREN; 45%) and SLEDD-associated (55%) CL well characterised the SLEDD data. Creatinine clearance (urine-collected; CLCRurine) was identified as significant factor on CLREN. Continuous infusions, specifically 2 g q24h for CLCRurine 0-25 mL/min and 3 g q24h for CLCRurine 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.
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.
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