Department of Pharmacy, NYU Langone Health, New York, NY, USA.
Division of Infectious Diseases, Department of Medicine, NYU Langone Health, New York, NY, USA.
J Intensive Care Med. 2020 Aug;35(8):763-771. doi: 10.1177/0885066618784264. Epub 2018 Jun 28.
Extended infusion (EI) administration of β-lactams can improve target attainment in critically ill patients with altered pharmacokinetics/pharmacodynamics. To optimize meropenem dosing in patients with severe sepsis/septic shock, our Antimicrobial Stewardship Program implemented a EI meropenem (EIM) protocol in an 18-bed Medical Intensive Care Unit in March 2014. In this retrospective study, we compared intensive care unit (ICU) mortality and clinical response in patients who received meropenem for ≥72 hours administered per EIM protocol of 1 g over 3 hours every 8 hours versus intermittent infusion (IIM) protocol of 500 mg over 30 minutes every 6 hours. Age, weight, comorbidities, severity of illness, and vasopressor use were comparable between groups (EIM protocol n = 52, IIM protocol n = 96). The IIM protocol group had higher rates of renal dose adjustment at meropenem initiation. Among 56 identified gram-negative (GN) pathogens, 94% had meropenem minimal inhibitory concentration ≤0.25 mg/L. The ICU mortality was lower (19 vs 37%; = .032) and clinical response was higher (83% vs 46%; < .01) in the EIM protocol versus IIM protocol group. Total vasopressor days were shorter (2 vs 3 days; = .038), and white blood cell normalization rate was higher (87% vs 51%; < .01) in the EIM protocol versus IIM protocol group. There was no difference in days of mechanical ventilation, duration of therapy, and ICU stay. The IIM protocol was also identified as an independent risk factor associated with ICU mortality (hazard ratio: 3.653, 95% confidence interval: 1.689-7.981; = .001) after adjusting for Sequential Organ Failure Assessment score. In this cohort of patients with severe sepsis/septic shock and highly susceptible GN pathogens, there was improved mortality and clinical response in the EIM protocol group.
延长输注（EI）β-内酰胺类药物可改善药代动力学/药效学改变的危重症患者的目标达标率。为了优化重症脓毒症/脓毒性休克患者的美罗培南剂量，我们的抗菌药物管理项目于 2014 年 3 月在 18 张床位的内科重症监护病房实施了 EI 美罗培南（EIM）方案。在这项回顾性研究中，我们比较了接受 EIM 方案（每 8 小时输注 1 克美罗培南 3 小时）和 II 方案（每 6 小时输注 500 毫克美罗培南 30 分钟）的患者的 ICU 死亡率和临床反应。两组患者的年龄、体重、合并症、疾病严重程度和血管加压素使用情况相当（EIM 方案组 52 例，IIM 方案组 96 例）。EIM 方案组在开始使用美罗培南时更频繁地进行肾剂量调整。在 56 种鉴定的革兰氏阴性（GN）病原体中，94%的美罗培南最小抑菌浓度≤0.25mg/L。EIM 方案组 ICU 死亡率较低（19% vs 37%；.032），临床反应较高（83% vs 46%； <.01）。EIM 方案组的总血管加压素天数较短（2 天 vs 3 天； =.038），白细胞恢复正常的比例较高（87% vs 51%； <.01）。两组患者的机械通气时间、治疗持续时间和 ICU 住院时间无差异。在调整序贯器官衰竭评估评分后，IIM 方案也是与 ICU 死亡率相关的独立危险因素（危险比：3.653，95%置信区间：1.689-7.981； =.001）。在这组患有严重脓毒症/脓毒性休克和高度敏感 GN 病原体的患者中，EIM 方案组的死亡率和临床反应得到了改善。
