Integrated pharmacokinetic-pharmacodynamic modeling to evaluate empiric carbapenem therapy in bloodstream infections.
Integrated pharmacokinetic-pharmacodynamic modeling to evaluate empiric carbapenem therapy in bloodstream infections.
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DOI：
10.2147/idr.s168191
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发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Kwa, Andrea L
中科院分区：
文献类型：
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作者：
Lim, Tze-Peng;Wang, Reyna;Kwa, Andrea L
治疗由多重耐药（MDR）革兰氏阴性菌（GNB）引起的医院内血流感染（BSI）具有挑战性。抗生素耐药性的上升，特别是在超广谱β-内酰胺酶生产中，无意中增加了经验性碳青霉烯类药物的消耗。在新加坡，三种抗假单胞菌碳青霉烯类（亚胺培南、美罗培南[MER]和多利培南[DOR]）可用于治疗MDR GNB。本研究旨在确定最佳的经验性碳青霉烯给药方案（CDR），并评估其成本效益的GNB-BSI面对增加的MDR GNB。方法：碳青霉烯最低抑菌浓度（MIC）生成的非重复GNB-BSI在2013-2014年从两家医院获得。使用Monte Carlo模拟来评估各种CDR的累积响应分数（CFR），使用高于MIC 40%的时间百分比（%T > MIC 40%）作为功效的药代动力学（PK）-药效学（PD）参数。碳青霉烯类抗生素的成本基于患者的抗生素成本。抗生素的成本-效果计算为每日药物总成本/CFR。结果：共收集了1,140株血流分离株。其中鲍曼不动杆菌116株，铜绿假单胞菌237株，肠杆菌787株。所有CDR均达到约40、约80和≥90%的抗A CFR。鲍曼不动杆菌、铜绿假单胞菌和肠杆菌科。针对铜绿假单胞菌，MER 2 g每8 h输注3 h，DOR 1 g每8 h输注4 h，分别达到CFR 84和81%。对肠杆菌科，MER 2克，每8小时输注超过3小时的成本是最低的三种碳青霉烯类在0.40美元/百分比的CFR。结论：本研究表明的实用程序的PK-PD建模制定的最佳选择的一个具有成本效益的经验性CDR抗生素指南和处方列入。研究结果支持选择高MER剂量的长时间输注作为我们机构GNB-BSI的经验性覆盖范围。
OBJECTIVES: Treatment for nosocomial bloodstream infections (BSI) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) is challenging. Rising antimicrobial resistance, especially in extended spectrum beta-lactamase production, inadvertently increases empiric carbapenem consumption. Three antipseudomonal carbapenems (imipenem, meropenem [MER], and doripenem [DOR]) are available commercially against MDR GNB in Singapore. The study aims to determine the most optimal empiric carbapenem dosing regimens (CDR) and evaluate their cost-effectiveness for GNB-BSI in the face of increasing MDR GNB.METHODS: Carbapenem minimum inhibitory concentrations (MICs) were generated for non-repeat GNB-BSI obtained in 2013-2014 from two hospitals. Monte Carlo simulations were used to assess the cumulative fraction of response (CFR) of various CDRs using the percentage of time above MIC for 40% (%T > MIC of 40%) as the pharmacokinetic (PK)-pharmacodynamic (PD) parameter for efficacy. Carbapenem costs were based on patient antibiotic costs. Antibiotic cost-effectiveness was calculated as total daily drug cost/CFR.RESULTS: A total of 1,140 bloodstream isolates were collected. They comprised 116 Acinetobacter baumannii, 237 Pseudomonas aeruginosa, and 787 Enterobacteriaceae. All CDRs achieved ~40, ~80, and ≥90% CFRs against A. baumannii, P. aeruginosa, and Enterobacteriaceae, respectively. Against P. aeruginosa, MER 2 g every 8 h infused over 3 h and DOR 1 g every 8 h infused over 4 h achieved CFRs 84 and 81%, respectively. Against Enterobacteriaceae, the cost of MER 2 g every 8 h infused over 3 h was the lowest among the three carbapenems at $0.40/percentage of CFR.CONCLUSION: This study demonstrates the utility of PK-PD modeling to formulate the optimal selection of a cost-effective empiric CDR in antibiotics guidelines and formulary inclusion. The findings support the selection of high MER doses of prolonged infusions as empiric coverage for GNB-BSI in our institutions.