Department of Nephrology, Dialysis and Transplantation, International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Azienda ULSS 8 Berica, Vicenza, Italy.
Department of Anaesthesia, Critical Care and Emergency, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Clin Pharmacokinet. 2024 Aug;63(8):1167-1176. doi: 10.1007/s40262-024-01397-w. Epub 2024 Aug 5.
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).
Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cl) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days.
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 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 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.
MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.
肾脏替代疗法（RRT）在抗菌药物的清除中起着至关重要的作用，特别是对于血浆蛋白结合率低、分布容积小、亲水性低的低分子量药物。中分子量（MCO）膜代表了透析技术的新一代，增强了弥散模式的功效，并将截留分子量从 30 kDa 提高到 45 kDa，这对于中分子的清除至关重要。这项单中心随机交叉先导研究旨在评估与标准高通量膜（HFM-CVVHDF）连续静脉-静脉血液透析滤过（CVVHDF）相比，连续血液透析（MCO-CVVHD）中使用 MCO 膜对哌拉西林、他唑巴坦和美罗培南清除率的影响。
20 名患者被随机分配接受 MCO-CVVHD 治疗，然后接受 HFM-CVVHDF 治疗，或反之。在不同时间点评估提取率（ER）、流出液清除率（Cl）和治疗效率。在两种治疗日测量抗生素最低血浆水平。
与 MCO-CVVHD 相比，HFM-CVVHDF 对美罗培南（β=−8.90（95%CI−12.9 至−4.87），p<0.001）和他唑巴坦（β=−8.29（95%CI−13.5 至−3.08），p=0.002）的 ER 更大，且对每种抗生素的 Cl 也更大（美罗培南β=−10,206（95%CI−14,787 至−5787），p=0.001）；他唑巴坦β=−4551（95%CI−7781 至−1322），p=0.012）；哌拉西林β=−3913（95%CI−6388 至−1437），p=0.002），即使存在携带效应，也会影响美罗培南和他唑巴坦的 Cl。任何抗生素的最低血浆浓度或效率均无差异。哌拉西林（β=−38.1（95%CI−47.9 至−28.3），p<0.001）和他唑巴坦（β=−4.45（95%CI−6.17 至−2.72），p<0.001）在第二天的最低血浆浓度均低于第一天，与过滤器类型无关。
MCO 与 HFM 相比，在体内对哌拉西林、他唑巴坦和美罗培南的清除率相当。
