Kaska Milan, Havel Eduard, Selke-Krulichova Iva, Safranek Petr, Bezouska Jan, Martinkova Jirina
Department of Surgery, University Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic.
Academic Department of Surgery, Faculty of Medicine in Hradec Kralove, Charles University and Department of Surgery, University Hospital, Sokolska 581, 50005 Hradec Kralove, Czech Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2018 Sep;162(3):219-226. doi: 10.5507/bp.2018.011. Epub 2018 Mar 27.
Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Cl) and cumulative fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB).
In this prospective observational pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical Intensive Care Unit (ICU) were enrolled. The primary PK/PD target was free antibiotic concentrations above MIC at 100% of the dosing interval (100%fT>MIC) to obtain maximum bactericidal activity. Drug concentration was measured using liquid chromatography-tandem mass spectrometry.
The treatment of both 8 septic patients with IV extended ME dosing 2 g/3 h q8 h and 10 polytraumatized patients with IV intermittent PIP/TZB dosing 4.0/0.5 g q8 h was monitored. 8/18 patients (44%) manifested augmented renal clearence (ARC) where Cl ≥130 mL/min/1.73 m. Maximum changes were reported on days 2-3: the median positive CFB followed by the large median volume of distribution: Vd=70.3 L (41.9-101.5), Vd = 46.8 L (39.7-60.0). 100%fT>MIC was achieved in all patients on ME (aged ≥60 years), and only in two patients (non-ARC, aged ≥65 years) out of 10 on PIP/TZB. A mixed model analysis revealed positive relationship of CFB with Vd (P=0.021).
Assuming that the positive correlation between CFB and Vd exists for piperacillin in the setting of the pathological state, then CFB should predict Vd across subjects at each and every time point.
接受积极液体复苏并经验性使用水溶性时间依赖性β-内酰胺类抗生素治疗的重症患者存在血浆浓度低于治疗水平的风险。本研究的目的是评估两个协变量——肌酐清除率（Cl）和累积液体平衡（CFB）对美罗培南（ME）或哌拉西林/他唑巴坦（PIP/TZB）治疗一周内药代动力学/药效学（PK/PD）目标达成情况的影响。
在这项前瞻性观察性药代动力学（PK）研究中，纳入了18名入住外科重症监护病房（ICU）的重症患者。主要的PK/PD目标是在给药间隔的100%时间内游离抗生素浓度高于最低抑菌浓度（100%fT>MIC），以获得最大杀菌活性。使用液相色谱-串联质谱法测量药物浓度。
监测了8名脓毒症患者静脉注射延长剂量美罗培南2 g/3 h q8 h以及10名多发伤患者静脉注射间歇剂量哌拉西林/他唑巴坦4.0/0.5 g q8 h的治疗情况。18名患者中有8名（44%）表现出肾脏清除率增加（ARC），即Cl≥130 mL/min/1.73 m²。最大变化出现在第2至3天：中位数正性CFB随后是较大的分布容积中位数：Vd = 70.3 L（41.9 - 101.5），Vd = 46.8 L（39.7 - 60.0）。所有接受美罗培南治疗的患者（年龄≥60岁）均达到100%fT>MIC，而在接受哌拉西林/他唑巴坦治疗的10名患者中，只有两名患者（非ARC，年龄≥65岁）达到该目标。混合模型分析显示CFB与Vd呈正相关（P = 0.021）。
假设在病理状态下哌拉西林的CFB与Vd之间存在正相关，那么CFB应该能够预测每个时间点所有受试者的Vd。
