Department of Infection Control, Faculty of Medicine, Clinical Hospital, University of São Paulo, São Paulo, Brazil.
Department of Infection Control, Faculty of Medicine, Clinical Hospital, University of São Paulo, São Paulo, Brazil.
Clin Ther. 2020 Apr;42(4):625-633. doi: 10.1016/j.clinthera.2020.02.011. Epub 2020 Mar 19.
Antibiotic dosing is challenge in critically ill patients undergoing renal replacement therapy. Our aim was to evaluate the pharmacokinetic and pharmacodynamic (PK/PD) characteristics of meropenem and vancomycin in patients undergoing SLED.
Consecutive ICU patients undergoing SLED and receiving meropenem and/or vancomycin were prospectively evaluated. Serial blood samples were collected before, during, and at the end of SLED sessions. Antimicrobial concentrations were determined using a validated HPLC method. Noncompartmental PK analysis was performed. AUC was determined for vancomycin. For meropenem, time above MIC was calculated.
A total of 24 patients receiving vancomycin and 21 receiving meropenem were included; 170 plasma samples were obtained. Median serum vancomycin and meropenem concentrations before SLED were 24.5 and 28.0 μg/mL, respectively; after SLED, 14 and 6 μg/mL. Mean removal was 42% with vancomycin and 78% with meropenem. With vancomycin, 19 (83%), 16 (70%), and 15 (65%) patients would have achieved the target (AUC >400) considering MICs of 1, 2, and 4 mg/L, respectively. With meropenem, 17 (85%), 14 (70%), and 10 (50%) patients would have achieved the target (100% of time above MIC) if infected with isolates with MICs of 1, 4, and 8 mg/L, respectively.
SLED clearances of meropenem and vancomycin were 3-fold higher than the clearance described by continuous methods. Despite this finding, overall high PK/PD target attainments were obtained, except for at higher MICs. We suggest a maintenance dose of 1 g TID or BID of meropenem. With vancomycin, a more individualized approach using therapeutic drug monitoring should be used, as commercial assays are available.
在接受肾脏替代治疗的危重症患者中，抗生素的给药剂量是一个挑战。我们的目的是评估连续肾脏替代治疗（SLED）患者中美罗培南和万古霉素的药代动力学和药效学（PK/PD）特征。
连续评估接受 SLED 并接受美罗培南和/或万古霉素的 ICU 患者。在 SLED 治疗前后和结束时采集连续的血样。使用验证的 HPLC 方法测定抗生素浓度。进行非房室 PK 分析。测定万古霉素的 AUC。对于美罗培南，计算 MIC 以上时间。
共纳入 24 例接受万古霉素和 21 例接受美罗培南的患者；共获得 170 个血浆样本。SLED 前血清万古霉素和美罗培南的中位数浓度分别为 24.5 和 28.0μg/mL；SLED 后分别为 14 和 6μg/mL。万古霉素的平均清除率为 42%，美罗培南为 78%。对于万古霉素，考虑到 MIC 分别为 1、2 和 4mg/L，19 例（83%）、16 例（70%）和 15 例（65%）患者将达到目标（AUC>400）。对于美罗培南，如果感染 MIC 分别为 1、4 和 8mg/L的分离株，17 例（85%）、14 例（70%）和 10 例（50%）患者将达到目标（100%MIC 以上时间）。
SLED 对美罗培南和万古霉素的清除率是连续方法描述的清除率的 3 倍。尽管如此，除了更高的 MIC 外，总体上还是获得了很高的 PK/PD 目标实现率。我们建议美罗培南的维持剂量为 1g TID 或 BID。对于万古霉素，应使用治疗药物监测进行更个体化的治疗，因为有商业检测方法。
