Midwestern University Chicago College of Pharmacy, Downers Grove, USA; Northwestern Memorial Hospital, Chicago, USA; Midwestern University Chicago College of Pharmacy Pharmacometrics Center of Excellence, Downers Grove, USA.
UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Australia; Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, University of Queensland, Australia.
Int J Antimicrob Agents. 2020 Nov;56(5):106151. doi: 10.1016/j.ijantimicag.2020.106151. Epub 2020 Aug 31.
There has been interest in administering cefepime, a β-lactam antibiotic, via intravenous push (IVP) as a means to improve time to first-dose antibiotic and reduce cost; however, the downstream impacts on antibiotic exposure and pharmacodynamic efficacy need to be further evaluated.
This study used a population pharmacokinetic model for cefepime and simulated exposures to predict the pharmacodynamic (PD) effect for cefepime regimens administered via IVP or 30-minute intermittent infusion in adults with different renal functions. FDA-approved adult dosages of 1-2 g every 8 or 12 hours were compared. This study aimed to compare the absolute difference in pharmacodynamic probability of target attainment (PTA) between IVP and intermittent infusion, defined as free cefepime concentrations above organism MIC for ≥ 70% of the time.
At MICs of 0.25-0.5 mg/L, absolute differences in PTA were observed, with a reduction as great as 2.3% (89% to 86.7% for 30-minute intermittent infusion and IVP, respectively). At MICs of 1-4 mg/L, 30-minute intermittent infusion and IVP exhibited PTA differences as great as 5.4%, from 89.4% to 84%, respectively. At MICs of ≥8 mg/L, similar absolute differences existed; however, no regimen achieved a PTA >70%. Across renal function strata of 60, 100 and 140 mL/minute (within the same dosing group and MICs), better renal function lowered PTAs.
Simulations demonstrated that IVP cefepime resulted in lower PTAs than traditional intermittent infusion among a subset of elevated MICs. Clinicians should exercise caution in IVP strategy, as unintended clinical consequences are possible.
人们对通过静脉推注（IVP）给予头孢吡肟（一种β-内酰胺类抗生素）以改善首次给药抗生素的时间并降低成本的方法很感兴趣；然而，其对抗生素暴露和药效学疗效的影响需要进一步评估。
本研究使用头孢吡肟的群体药代动力学模型来模拟暴露情况，以预测不同肾功能成人通过 IVP 或 30 分钟间歇性输注给予头孢吡肟方案的药效学（PD）效果。比较了 FDA 批准的成人剂量，即每 8 或 12 小时 1-2 克。本研究旨在比较 IVP 和间歇性输注之间的药效学目标浓度时间百分比（T＞MIC）的绝对差异，定义为游离头孢吡肟浓度超过生物体 MIC 的时间达到 70%以上。
在 MIC 值为 0.25-0.5 mg/L 时，观察到 PTA 的绝对差异，最大减少 2.3%（30 分钟间歇性输注和 IVP 分别为 89%和 86.7%）。在 MIC 值为 1-4 mg/L 时，30 分钟间歇性输注和 IVP 的 PTA 差异最大可达 5.4%，分别为 89.4%和 84%。在 MIC 值≥8 mg/L 时，存在相似的绝对差异；然而，没有一种方案达到 PTA＞70%。在 60、100 和 140 mL/min（同一剂量组和 MIC 下）的肾功能分层中，更好的肾功能降低了 PTA。
模拟结果表明，在一部分 MIC 升高的患者中，与传统间歇性输注相比，IVP 头孢吡肟导致 PTA 降低。临床医生在采用 IVP 策略时应谨慎，因为可能会产生意想不到的临床后果。
