Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy.
Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy.
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推荐的β-内酰胺方案对于接受连续肾脏替代治疗的脓毒症患者来说是不够的。
DOI：
10.1186/cc10257
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Jacobs F
中科院分区：
文献类型：
--
作者：
Seyler L;Cotton F;Taccone FS;De Backer D;Macours P;Vincent JL;Jacobs F
败血症是抗生素药代动力学发生重要变化的原因。脓毒症患者常用的连续性肾脏替代疗法(CRRT)可能进一步促进药代动力学的改变。目前CRRT期间抗生素剂量的建议结合了从不同患者群体中获得的数据，其中使用了不同的CRRT设备和技术。我们研究了这些建议是否符合接受CRRT的感染性休克患者广谱抗生素水平的最佳药代动力学标准。这项开放的前瞻性研究纳入了连续接受CRRT治疗的患者，他们接受美罗培南(MEM)、哌拉西林-他唑巴坦(TZP)、头孢吡肟(FEP)或头孢他啶(CAZ)治疗。这些抗生素的血药浓度在给药前(t=0)和给药后1、2、5、6或12小时(取决于β-内酰胺方案)用高效液相色谱法测定。一系列的测量被分成在治疗的早期阶段(从第一次剂量起48小时)和之后(48小时)进行的测量。共采集53例患者69份血清标本，其中MEM组17例，TZP组16例，FEP组8例，CAZ组12例。血药浓度维持在假单胞菌最低抑菌浓度的4倍以上。81%的患者接受MEM治疗，71%的患者接受TZP治疗，53%的患者接受CAZ治疗，0%的患者接受FEP治疗。治疗48小时后的蓄积仅对MEM有显著意义。在接受CRRT的脓毒症患者中，针对铜绿假单胞菌的推荐剂量的β-内酰胺类药物适用于MEM，但不适用于TZP、FEP和CAZ；对于后两种药物，应使用更高剂量和/或更长时间的输液来优化血清浓度。
Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient populations in which different CRRT devices and techniques have been used. We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT. This open, prospective study enrolled consecutive patients treated with CRRT and receiving either meropenem (MEM), piperacillin-tazobactam (TZP), cefepime (FEP) or ceftazidime (CAZ). Serum concentrations of these antibiotics were determined by high-performance liquid chromatography from samples taken before (t = 0) and 1, 2, 5, and 6 or 12 hours (depending on the β-lactam regimen) after the administration of each antibiotic. Series of measurements were separated into those taken during the early phase (< 48 hours from the first dose) of therapy and those taken later (> 48 hours). A total of 69 series of serum samples were obtained in 53 patients (MEM, n = 17; TZP, n = 16; FEP, n = 8; CAZ, n = 12). Serum concentrations remained above four times the minimal inhibitory concentration for Pseudomonas spp. for the recommended time in 81% of patients treated with MEM, in 71% with TZP, in 53% with CAZ and in 0% with FEP. Accumulation after 48 hours of treatment was significant only for MEM. In septic patients receiving CRRT, recommended doses of β-lactams for Pseudomonas aeruginosa are adequate for MEM but not for TZP, FEP and CAZ; for these latter drugs, higher doses and/or extended infusions should be used to optimise serum concentrations.
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影响因子：
11.8
作者：
Lodise, Thomas P., Jr.;Lomaestro, Ben;Drusano, George L.
通讯作者：
Drusano, George L.
影响因子：
8.8
作者：
Levy, MM;Fink, MP;Ramsay, G
通讯作者：
Ramsay, G
影响因子：
4.9
作者：
Li, Chonghua;Du, Xiaoli;Nicolau, David P.
通讯作者：
Nicolau, David P.
影响因子：
4.9
作者：
Malone, RS;Fish, DN;Teitelbaum, I
通讯作者：
Teitelbaum, I
影响因子：
38.9
作者：
Langgartner, Julia;Vasold, Antje;Kees, Frieder
通讯作者：
Kees, Frieder