HealthTrust Supply Chain, Richmond, VA, USA.
Ann Pharmacother. 2021 Jul;55(7):846-855. doi: 10.1177/1060028020971216. Epub 2020 Nov 4.
The optimal daptomycin dose for vancomycin-resistant remains unclear. Dosing of 8 to 12 mg/kg/d has been recommended to improve outcomes, but literature suggests fixed dosing may improve methicillin-resistant bacteremia pharmacodynamic (PD) targets.
This study sought to evaluate weight-based versus fixed dosing of daptomycin based on pharmacokinetic and PD (PK-PD) targets in vancomycin-resistant bacteremia.
PK-PD analyses were conducted using previously published PK models for daptomycin. Probability of target attainment (PTA) was assessed for 8 to 12 mg/kg/d and various fixed doses. The percentage of simulated participants who achieved a free area under the concentration-time curve from 0 to 24 hours to minimum inhibitory concentration ratio (AUC/MIC) >27.43 for susceptible dose-dependent (SDD) MICs and the probability of a minimum concentration () > 24.3 mg/L were calculated.
At MICs ≤2 mg/L, fixed doses had the best overall PTA. At the SDD breakpoint of 4 mg/L, all weight-based doses had <60% PTA. A fixed dose of 1500 mg/d was necessary for >/= 90% PTA at higher MICs considered SDD; however, this dose had elevated risks of ≥24.3 mg/L.
Fixed doses were more likely to achieve a AUC/MIC of 27.43 than weight-based doses up to 12 mg/kg/d. However, fixed doses necessary for 90% PTA against SDD isolates with higher MICs were associated with elevated risks of toxicity. A reevaluation of Clinical Laboratory Standards Institute breakpoints may need to be considered, with an emphasis on lowering the SDD breakpoint to 1 mg/L.
万古霉素耐药 的最佳达托霉素剂量仍不清楚。为了改善疗效，建议给予 8 至 12mg/kg/d 的剂量，但文献表明固定剂量可能改善耐甲氧西林 菌血症的药代动力学/药效学（PK-PD）目标。
本研究旨在评估基于药代动力学和 PD（PK-PD）目标的万古霉素耐药 菌血症的体重剂量与固定剂量的达托霉素。
使用先前发表的达托霉素 PK 模型进行 PK-PD 分析。评估 8 至 12mg/kg/d 和各种固定剂量的目标达标率（PTA）。计算达到最低抑菌浓度比值（AUC/MIC）>27.43 的敏感剂量依赖性（SDD）MICs 的模拟参与者的百分比和概率，以及达到最小浓度（ ）>24.3mg/L 的概率。
在 MICs≤2mg/L 时，固定剂量的总体 PTA 最佳。在 SDD 折点 4mg/L 时，所有体重剂量的 PTA<60%。在考虑为 SDD 的较高 MIC 时，需要固定剂量 1500mg/d 才能实现>90%的 PTA，但该剂量会增加 ≥24.3mg/L 的风险。
固定剂量比体重剂量更有可能达到 27.43 的 AUC/MIC。然而，对于较高 MIC 的 SDD 分离株，实现 90%PTA 所需的固定剂量与毒性增加的风险相关。可能需要重新评估临床实验室标准研究所的折点，重点是将 SDD 折点降低至 1mg/L。
