Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections.
Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections.
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DOI：
10.2147/cpaa.s96143
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Takeda Y
中科院分区：
文献类型：
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作者：
Matsumoto K;Watanabe E;Kanazawa N;Fukamizu T;Shigemi A;Yokoyama Y;Ikawa K;Morikawa N;Takeda Y
替柯planin是一种糖肽抗生素，已被用于治疗由革兰氏阳性菌引起的严重侵袭性感染。将药物浓度-时间曲线下面积(AUC)/最小抑制浓度（MIC）确定为糖肽类抗生素的药代动力学-药效学（PK-PD）参数，与细菌学反应和临床结果相关。虽然需要基于PK-PD的优化给药方案，但尚未进行teicoplanin对耐甲氧西林金黄色葡萄球菌（MRSA）感染的PK-PD分析。因此，本研究对MRSA感染患者进行了检查，这些患者接受了替柯planin治疗，以确定目标AUC/MIC比。本研究回顾性评估了鹿儿岛大学医院46例MRSA感染患者teicoplanin治疗的常规治疗药物监测（TDM）数据。采用荧光极化免疫分析系统测定替柯planin的血清浓度，并使用贝叶斯PK估计24小时AUC （AUC24）。采用标准琼脂稀释法测定替柯planin的MIC值。通过定量评估，对替柯planin的效果进行了细菌学评价。有无细菌学反应的AUC24/MIC比值分别为926.6±425.2µg·h/mL （n=34）和642.2±193.9µg·h/mL （n=12， P<0.05）。在logistic回归分析的基础上，AUC24/MIC比值为500µg·h/mL、700µg·h/mL和900µg·h/mL时，治疗成功概率分别为0.50、0.72和0.87。此外，通过Kaplan-Meier曲线分析，AUC24/MIC比值≥900导致的细菌学反应明显强于AUC24/MIC比值<900。这些结果表明，AUC24/MIC比值≥900µg·h/mL才能保证充分的细菌学反应。
Teicoplanin is a glycopeptide antibiotic that has been used to treat serious, invasive infections caused by Gram-positive bacteria. The area under the drug concentration–time curve (AUC)/minimum inhibitory concentration (MIC) was identified as a pharmacokinetic–pharmacodynamic (PK–PD) parameter of glycopeptide antibiotics that correlated with bacteriological responses and clinical outcomes. Although optimized dosing regimens based on PK–PD are needed, a PK–PD analysis of teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA) infections has not yet been performed. Thus, this study examined patients with MRSA infections, who were administered with teicoplanin in order to determine the target AUC/MIC ratio. This study retrospectively assessed data obtained as part of our routine therapeutic drug monitoring (TDM) of teicoplanin therapy in 46 patients with MRSA infections at Kagoshima University Hospital. Serum concentrations of teicoplanin were determined using a fluorescence polarization immunoassay system and used for a Bayesian PK estimation to estimate AUC for 24 hours (AUC24). The MIC value for teicoplanin was determined using a standardized agar dilution method. The effects of teicoplanin were evaluated in terms of bacteriological responses by a quantitative assessment. The estimated AUC24/MIC ratios with and without bacteriological responses were 926.6±425.2 µg·h/mL (n=34) and 642.2±193.9 µg·h/mL, respectively (n=12; P<0.05). On the basis of a logistic regression analysis, AUC24/MIC ratios of 500 µg·h/mL, 700 µg·h/mL, and 900 µg·h/mL gave probabilities of treatment success of 0.50, 0.72, and 0.87, respectively. Furthermore, using the Kaplan–Meier curve analysis, an AUC24/MIC ratio of ≥900 led to a significantly stronger bacteriological response than an AUC24/MIC ratio of <900. These results suggest that an AUC24/MIC ratio of ≥900 µg·h/mL is required to ensure a sufficient bacteriological response.