Department of Clinical and Administrative Pharmacy Sciences Howard University College of Pharmacy, Washington, D.C., USA.
Faculty of Pharmacy, Siam University, Bangkok, Thailand.
J Crit Care. 2021 Jun;63:154-160. doi: 10.1016/j.jcrc.2020.09.018. Epub 2020 Sep 24.
To determine appropriate dosing of levofloxacin in critically ill patients receiving continuous renal replacement therapy (CRRT).
All necessary pharmacokinetic and pharmacodynamic parameters from critically ill patients were obtained to develop mathematical models with first order elimination. Levofloxacin concentration-time profiles were calculated to determine the efficacy based on the probability of target attainment (PTA) of AUC/MIC ≥50 for Gram-positive and AUC/MIC ≥125 for Gram-negative infections. A group of 5000 virtual patients was simulated and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens were defined as the dose achieved target PTA at least 90% of the virtual patients.
No conventional, FDA approved regimens achieved at least 90% of PTA for Gram-negative infection with Pseudomonas aeruginosa at MIC of 2 mg/L. The successful dose (1750 mg on day 1, then 1500 mg q 24 h) was far exceeded the maximum FDA-approved doses. For Gram-positive infections, a levofloxacin 750 mg q 24 h was sufficient to attain PTA target of ~90% at the MIC of 2 mg/L for Streptococcus pneumoniae.
Levofloxacin cannot be recommended as an empiric monotherapy for serious Gram-negative infections in patients receiving CRRT due to suboptimal efficacy.
确定接受连续肾脏替代治疗（CRRT）的危重症患者左氧氟沙星的适当剂量。
从危重症患者中获得所有必要的药代动力学和药效学参数，以建立一级消除的数学模型。计算左氧氟沙星浓度-时间曲线，以根据 AUC/MIC≥50 对革兰阳性感染和 AUC/MIC≥125 对革兰阴性感染的目标浓度概率（PTA）来确定疗效。使用蒙特卡罗模拟对模型中的每个剂量对 5000 个虚拟患者进行模拟和测试。将达到目标 PTA 的至少 90%的虚拟患者的剂量定义为最佳给药方案。
对于 MIC 为 2mg/L 的铜绿假单胞菌引起的革兰阴性感染，没有常规的、FDA 批准的方案能达到至少 90%的 PTA。成功的剂量（第 1 天 1750mg，然后每天 1500mg）远远超过了 FDA 批准的最大剂量。对于革兰阳性感染，左氧氟沙星 750mg q 24h 足以达到 MIC 为 2mg/L 时的 PTA 目标约 90%。
由于疗效不佳，左氧氟沙星不能作为接受 CRRT 的患者严重革兰阴性感染的经验性单药治疗。
