Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia
Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia
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DOI：
10.1097/01.ccm.0000150265.42067.4c
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发表时间：
2005-01-01
影响因子：
8.8
通讯作者：
Allaouchiche, B
中科院分区：
文献类型：
--
作者：
Boselli, E;Breilh, D;Allaouchiche, B
目标：为了确定稳态血浆和上皮衬里液浓度静脉注射左氧氟沙星，500毫克，每天一次或两次在重症患者严重的社区获得性pneumonia.Design：前瞻性，开放标签研究。设定：重症监护室和临床药代动力学实验室在两所大学hospital.Patients：24例成人患者严重communityacquired肺炎和接受机械通气enrolled.Interventions：所有受试者接受1小时静脉输注500毫克左氧氟沙星每日一次或两次。血浆和上皮衬里液左氧氟沙星浓度在治疗2天后用高效液相色谱法在稳态下测定。中位数（四分位距[IQR]）血浆和上皮衬里液左氧氟沙星峰浓度为12.6（IQR，12.0-14.1）和11.9（IQR，8.7-13.7）mg/L，每日一次组和19.7每日两次组中的IQR，19.0-22.0）和17.8（IQR，16.2-23.5）mg/L，显示两组中的肺渗透百分比>100%。全身暴露中位数（lQR）为151（IQR，137-174）和416（IQR，406-472）mg-hr/L，分别在每日一次和每日两次组中。我们的研究结果表明，在接受机械通气并患有严重社区获得性肺炎和肌酐清除率>40 mL/min的危重患者中，每天一次和两次给予500 mg静脉内左氧氟沙星允许超过预测结果的药效学阈值（即，最低抑菌浓度值小于或等于1 mg/L和>1 mg/L的病原体在血清和上皮衬里液中的峰浓度与最低抑菌浓度比值>10或浓度-时间曲线下面积与最低抑菌浓度比值>125 h）。
Objective: To determine the steady-state plasma and epithelial lining fluid concentrations of intravenous levofloxacin, 500 mg, administered once or twice daily in critically ill patients with severe community-acquired pneumonia.Design: Prospective, open-label study. Setting: An intensive care unit and a clinical pharmacokinetic laboratory in two university hospitals.Patients: Twenty-four adult patients with severe communityacquired pneumonia and receiving mechanical ventilation were enrolled.Interventions: All subjects received 1-hr intravenous infusions of 500 mg levofloxacin once or twice daily. The plasma and epithelial lining fluid levofloxacin concentrations were determined at steady-state after 2 days of therapy with high-performance liquid chromallography.Measurements and main results: The median (interquartile range [IQR]) plasma and epithelial lining fluid peak levofloxacin concentrations were 12.6 (IQR, 12.0-14.1) and 11.9 (IQR, 8.7-13.7) mg/L, respectively, in the once-daily group and 19.7 (IQR, 19.0-22.0) and 17.8 (IQR, 16.2-23.5) mg/L in the twice-daily group, showing a pulmonary percentage penetration of >100% in both groups. The median (lQR) total body exposures were 151 (IQR, 137-174) and 416 (IQR, 406-472) mg-hr/L, respectively, in the once-daily and twice-daily groups.Conclusions: Our results suggest that in critically ill patients who are receiving mechanical ventilation and have severe communityacquired pneumonia and creatinine clearance of >40 mL/min, the administration of 500 mg of intravenous levofloxacin once and twice daily allows for the exceeding of pharmacodynamic thresholds predictive of outcome (i.e., peak concentration to minimum inhibitory concentration ratio of >10 or area under concentration-time curve to minimal inhibitory concentration ratio of >125 hrs) both in serum and epithelial lining fluid for pathogens with minimum inhibitory concentration values of less than or equal to1 mg/L and >1 mg/L, respectively.