Infectious Disease Pharmacokinetics Laboratory, Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Antimicrob Agents Chemother. 2021 May 18;65(6). doi: 10.1128/AAC.00144-21.
Sepsis causes half of acute kidney injuries in the intensive care unit (ICU). ICU patients may need continuous renal replacement therapy (CRRT), which will affect their antimicrobial exposure. We aimed to build a cefepime population pharmacokinetic (PK) model in CRRT ICU patients and perform simulations to assess target attainment. Patients who were ≥18 years old, were admitted to the ICU, and received cefepime 2 g every 8 h as a 4-h infusion while on CRRT were enrolled prospectively. Samples were collected from the predialyzer ports, postdialyzer ports, and effluent fluid at 1, 2, 3, 4, and 8 h after the first dose and at steady state. Age, sex, weight, urine output, and CRRT parameters were recorded. Pmetrics was used for population PK and simulations. The target exposure was 100% of the dosing interval during which the free beta-lactam concentration is above the MIC (). Ten patients were included; their mean age was 53 years, and mean weight was 119 kg. Seventy percent were males. Cefepime was described by a five-compartment model. The downtime was applied to the CRRT flow rates, which were used to describe the rates of transfer between the compartments. At MICs of ≤8 mg/liter, intermittent infusion of 2 g cefepime every 8 h achieved good target attainment both early in therapy and at steady state. Only extended- and continuous-infusion regimens achieved good target attainment at MICs of 16 mg/liter. In conclusion, 2 g cefepime infused over 30 min followed by extended infusion of 2 g every 8 h achieved good target attainment at MICs of ≤16 mg/liter with different CRRT flow rates and may be considered in resistant bacterial infections.
脓毒症导致 ICU 中一半的急性肾损伤。 ICU 患者可能需要持续肾脏替代治疗 (CRRT)，这会影响他们的抗菌药物暴露。我们旨在建立 CRRT ICU 患者中头孢吡肟的群体药代动力学 (PK) 模型，并进行模拟以评估目标达成情况。前瞻性纳入年龄≥18 岁、入住 ICU 并在接受 CRRT 时接受头孢吡肟 2 g 每 8 小时输注 4 小时的患者。在首剂后 1、2、3、4 和 8 小时以及稳态时从预滤器端口、后滤器端口和流出液中采集样本。记录年龄、性别、体重、尿量和 CRRT 参数。使用 Pmetrics 进行群体 PK 和模拟。目标暴露为在游离β-内酰胺浓度高于 MIC 的给药间隔的 100%（）。纳入 10 例患者；他们的平均年龄为 53 岁，平均体重为 119 公斤。 70%为男性。头孢吡肟用五室模型描述。停机时间适用于 CRRT 流速，用于描述各室之间的转移速率。在 MICs≤8mg/l 时，每 8 小时间歇输注 2 g 头孢吡肟可在治疗早期和稳态时达到良好的目标达成率。只有延长和连续输注方案在 MICs 为 16mg/l 时才能达到良好的目标达成率。总之，在不同的 CRRT 流速下，30 分钟输注 2 g 头孢吡肟后延长输注 2 g 每 8 小时可达到 MICs≤16mg/l 的良好目标达成率，可能适用于耐药细菌感染。
