Fiorenza Ferrari, Paola Milla, Marco Sartori, Christian Zanza, Manfredi Tesauro, Yaroslava Longhitano, Annalisa De Silvestri, Chiara Abbruzzese, Silvia De Rosa, Sergio Lassola, Sara Samoni, Alessandra Brendolan, Monica Zanella, Vittorio Scaravilli, Giacomo Grasselli, Silvia Arpicco, Claudio Ronco
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This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF).</p><p><strong>Methods: </strong>Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cl<sub>eff</sub>) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days.</p><p><strong>Results: </strong>HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (β = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cl<sub>eff</sub> for each antibiotic (meropenem β = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (β = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (β = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cl<sub>eff</sub> for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (β = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type.</p><p><strong>Conclusion: </strong>MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":" ","pages":"1167-1176"},"PeriodicalIF":4.6000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antibiotics Removal during Continuous Renal Replacement Therapy in Septic Shock Patients: Mixed Modality Versus \\\"Expanded Haemodialysis\\\".\",\"authors\":\"Fiorenza Ferrari, Paola Milla, Marco Sartori, Christian Zanza, Manfredi Tesauro, Yaroslava Longhitano, Annalisa De Silvestri, Chiara Abbruzzese, Silvia De Rosa, Sergio Lassola, Sara Samoni, Alessandra Brendolan, Monica Zanella, Vittorio Scaravilli, Giacomo Grasselli, Silvia Arpicco, Claudio Ronco\",\"doi\":\"10.1007/s40262-024-01397-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF).</p><p><strong>Methods: </strong>Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cl<sub>eff</sub>) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days.</p><p><strong>Results: </strong>HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (β = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cl<sub>eff</sub> for each antibiotic (meropenem β = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (β = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (β = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cl<sub>eff</sub> for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (β = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type.</p><p><strong>Conclusion: </strong>MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.</p>\",\"PeriodicalId\":10405,\"journal\":{\"name\":\"Clinical Pharmacokinetics\",\"volume\":\" \",\"pages\":\"1167-1176\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Pharmacokinetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s40262-024-01397-w\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40262-024-01397-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/5 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
背景和目的：肾脏替代疗法（RRT）在清除抗菌药物方面发挥着关键作用，尤其是对血浆蛋白结合率低、分布容积低和亲水性低的低分子量药物。中截留（MCO）膜是新一代透析技术的代表，它提高了扩散模式的疗效，并将截留分子量从 30 kDa 提高到 45 kDa，这对清除中等分子至关重要。这项单中心随机交叉试验研究旨在评估与使用标准高通量膜的连续性静脉血液透析（HFM-CVVHDF）相比，使用 MCO 膜的连续性血液透析（MCO-CVVHD）对哌拉西林、他唑巴坦和美罗培南清除率的影响：20名患者随机接受MCO-CVVHD治疗，然后接受HFM-CVVHDF治疗，反之亦然。在不同时间间隔评估提取率（ER）、流出物清除率（Cleff）和治疗效率。测量了两个治疗日的抗生素最低血浆水平：HFM-CVVHDF与MCO-CVVHD相比，美罗培南（β = - 8.90 (95% CI - 12.9 to - 4.87)，p < 0.001）和他唑巴坦（β = - 8.29 (95% CI - 13.5 to - 3.08)，p = 0.002）的ER更高，每种抗生素的Cleff更高（美罗培南 β = - 10,206 (95% CI - 14,787 to - 5787)，p = 0.001）；他唑巴坦（β = - 4551 (95% CI - 7781 to - 1322)，p = 0.012）；哌拉西林（β = - 3913 (95% CI - 6388 to - 1437)，p = 0.002），即使携带效应影响了美罗培南和他唑巴坦的 Cleff。没有观察到任何抗生素的最低血浆浓度或有效率存在差异。哌拉西林（β = - 38.1 (95% CI - 47.9 to - 28.3)，p < 0.001）和他唑巴坦（β = - 4.45 (95% CI - 6.17 to - 2.72)，p < 0.001）在第二天的最低血浆浓度低于第一天，与过滤器类型无关：结论：MCO对哌拉西林、他唑巴坦和美罗培南的体内清除率与HFM相当。
Antibiotics Removal during Continuous Renal Replacement Therapy in Septic Shock Patients: Mixed Modality Versus "Expanded Haemodialysis".
Background and objective: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF).
Methods: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days.
Results: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (β = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cleff for each antibiotic (meropenem β = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (β = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (β = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (β = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type.
Conclusion: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.
期刊介绍：
Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics.
Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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