Hill David M, Yang Bing, Laizure S Casey, Boucher Bradley, Swanson Joseph M, Wood G Christopher, Hickerson William L, Liu Xiangxia, Velamuri Sai R
Department of Pharmacy, Regional One Health, 877 Jefferson Avenue, Memphis, TN 38103, USA.
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, TN 38163, USA.
J Burn Care Res. 2024 Jan 5;45(1):151-157. doi: 10.1093/jbcr/irad134.
Patients with augmented renal clearance (ARC) are a subset of critically ill patients including burn patients that exhibit increased renal elimination of medications beyond that of similarly injured patients. Currently approved maximum regimens of medications primarily eliminated by the kidney, such as cefepime (>90% unchanged in the urine), may be inadequate (eg, compromising the bactericidal activity of cefepime) in patients with ARC. Due to recent resource limitations, centers have changed infusion practices of commonly prescribed medications to intravenous push (IVP), potentially exacerbating the problem of maintaining bactericidal cefepime concentrations. The hypothesis of the study was patients with ARC are not currently achieving adequate target attainment, when receiving cefepime 2 g every 8 h IVP. Eight blood samples were collected from each patient, and concentrations measured via LC-MS/MS. WinNonlin (version 8.3) was used to estimate the pharmacokinetic parameters of cefepime and simulate plasma concentrations of cefepime in each of the ten subjects. Simulations of cefepime plasma concentrations produced by a 2 g dose given every 8 h and a 1 g dose given every 4 h were performed and the time above a MIC of 4 mg/L, 8 mg/L, and 16 mg/L compared. The 2 g every 8 h regimen remained above the breakpoints for 92%, 85%, and 71% of the dosing interval, respectively. The 1 g every 4 h regimen remained above the same breakpoints at a frequency of 100%, 99%, and 92% of the dosing interval. Giving cefepime 1 g every 4 h is a simple approach to increase the likelihood of maintaining the optimal bactericidal activity of cefepime in patients with ARC.
肾脏清除率增加（ARC）的患者是重症患者的一个子集，包括烧伤患者，这些患者对药物的肾脏清除能力比类似受伤的患者更强。目前批准的主要经肾脏消除的药物最大给药方案，如头孢吡肟（>90%以原形经尿液排出），在ARC患者中可能并不充分（例如，会损害头孢吡肟的杀菌活性）。由于最近资源有限，各医疗中心已将常用药物的输注方式改为静脉推注（IVP），这可能会加剧维持头孢吡肟杀菌浓度的问题。该研究的假设是，ARC患者每8小时静脉推注2g头孢吡肟时，目前无法达到足够的目标浓度。从每位患者采集8份血样，并通过液相色谱-串联质谱法（LC-MS/MS）测量浓度。使用WinNonlin（8.3版）估算头孢吡肟的药代动力学参数，并模拟10名受试者中每位受试者的头孢吡肟血浆浓度。对每8小时给予2g剂量和每4小时给予1g剂量所产生的头孢吡肟血浆浓度进行模拟，并比较高于4mg/L、8mg/L和16mg/L最低抑菌浓度（MIC）的时间。每8小时给予2g的给药方案在给药间隔的92%、85%和71%的时间内分别保持高于断点浓度。每4小时给予1g的给药方案在给药间隔的100%、99%和92%的时间内保持高于相同的断点浓度。每4小时给予1g头孢吡肟是一种简单的方法，可增加在ARC患者中维持头孢吡肟最佳杀菌活性的可能性。
