Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections
Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections
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DOI：
10.1128/aac.00294-06
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发表时间：
2007-05-01
影响因子：
4.9
通讯作者：
Nicolau, David P.
中科院分区：
文献类型：
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作者：
Li, Chonghua;Du, Xiaoli;Nicolau, David P.
对感染患者β -内酰胺药效学的研究很少。本研究采用分类回归树（CART）和logistic回归分析，对101例成年下呼吸道感染（LRTI）患者的药效学指标和药效学量进行分析，以确定哪些指标和药效学量是美罗南疗效的显著预测因子。利用人口学数据，采用经过验证的人群药代动力学模型预测研究患者的药代动力学参数和游离血清浓度。药效学指标[给药间隔中游离药物浓度保持在MIC以上的百分比（%fT > MIC），f（血清中最大药物浓度）(fC(max))/MIC,fC(min)]。/MIC，根据每位患者药物MIC最高的基线病原体计算f（浓度-时间曲线下面积）(fac)/MIC]。百分比fT > MIC, fC(max) /MIC, fC(min)/MIC和fac /MIC的中位数（范围）分别为100%(0至100%),728.8(0.8至15,777),19.9（0.01至278）和3,605.4（2.7至60,865.9）。CART确定了以下断点作为微生物反应的重要预测因子：>54% fT > MIC, fC(max)/ MIC > 383, fC(min)/MIC >5；fC-(min)/MIC > 5是临床反应的唯一显著预测因子。由于大多数LRTI患者达到100% fT > MIC，因此fC(min)/MIC是与成人LRTI患者美罗培南临床和微生物反应相关的具有统计学意义的参数。研究结果可用于优化美罗培南给药方案，以获得临床成功，并在临床实践中实现微生物根除。
Studies of beta-lactam pharmacodynamics in infected patients are sparse. In this study, classification and regression tree (CART) and logistic regression analyses were used to identify which pharmacodynamic indices and magnitudes were significant predictors of meropenem efficacy for 101 adult patients with lower respiratory tract infections (LRTI). Using demographic data, a validated population pharmacokinetic model was employed to predict pharmacokinetic parameters and free serum concentrations in the studied patients. Pharmacodynamic indices [percentage of the dosing interval that free drug concentrations remain above the MIC (%fT > MIC),f(maximum concentration of drug in serum) (fC(max))/MIC,fC(min)./MIC, and f(area under the concentration-time curve) (fAUC)/MIC] were calculated based on the baseline pathogen with the highest drug MIC for each patient. The median (range) of percent fT > MIC, fC(max) /MIC, fC(min)/MIC, and fAUC/MIC were 100% (0 to 100%), 728.8 (0.8 to 15,777), 19.9 (0.01 to 278), and 3,605.4 (2.7 to 60,865.9), respectively. CART identified the following breakpoints as significant predictors for microbiological response: >54% fT > MIC, a fC(max)/ MIC > 383, and a fC(min)/MIC > 5;fC-(min)/MIC > 5 was the only significant predictor of clinical response. Due to 100% fT > MIC achieved in the majority of LRTI patients, fC(min)/MIC was the statistically significant parameter associated with meropenem clinical and microbiological response in the adults with LRTI. The findings for LRTI patients can be applied to optimize meropenem dose regimens to achieve clinical success and microbiological eradication in clinical practice.