The University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia.
Intensive Care Services, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Clin Infect Dis. 2021 Apr 26;72(8):1369-1378. doi: 10.1093/cid/ciaa224.
The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets.
We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations.
We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively.
In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
在接受肾脏替代治疗（RRT）的危重症患者中，抗生素的最佳剂量仍不清楚。在这项研究中，我们描述了接受 RRT 的危重症患者的 RRT 技术和抗生素剂量的可变性，并将观察到的抗生素谷浓度与最佳目标相关联。
我们在 14 个国家的 29 个重症监护病房进行了一项前瞻性、观察性、多国、药代动力学研究。我们收集了人口统计学、临床和 RRT 数据。我们测量了美罗培南、哌拉西林他唑巴坦和万古霉素的谷浓度，并将其与高和低目标谷浓度相关联。
我们研究了 381 名患者，并获得了 508 个抗生素谷浓度。抗生素剂量方案、RRT 处方和估计的内源性肾功能存在广泛的差异（4-8 倍）。所有抗生素的总体中位数估计总肾清除率（eTRCL）为 50 毫升/分钟（四分位距 [IQR]，35-65），较高的 eTRCL 与所有抗生素的较低谷浓度相关（P <.05）。美罗培南的中位数（IQR）谷浓度为 12.1 毫克/升（7.9-18.8），哌拉西林为 78.6 毫克/升（49.5-127.3），他唑巴坦为 9.5 毫克/升（6.3-14.2），万古霉素为 14.3 毫克/升（11.6-21.8）。美罗培南、哌拉西林和万古霉素的谷浓度分别有 26%、36%和 72%的患者未能达到较高的目标范围，有 4%、4%和 55%的患者未能达到较低的目标范围。
在接受 RRT 治疗的危重症患者中，抗生素剂量方案、RRT 处方和 eTRCL 差异显著，导致抗生素浓度高度变化，许多患者未能达到治疗目标。
