Cefepime Tissue Penetration in Experimental Acute Pancreatitis

Cefepime Tissue Penetration in Experimental Acute Pancreatitis
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头孢吡肟在实验性急性胰腺炎中的组织渗透

DOI:
10.1097/00006676-200303000-00005
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发表时间:
2003
期刊:
影响因子:
2.9
通讯作者:
M. Büchler
M. Büchler
中科院分区:
医学4区
文献类型:
--
作者:
B. Gloor;M. Worni;O. Strobel;W. Uhl;O. Tcholakov;C. Müller;P. Stahel;S. Droz;M. Büchler

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前言抗生素治疗是重症急性胰腺炎治疗的基石。然而,目前使用的抗生素物质不同。在这项研究中,我们分析了两种急性胰腺炎模型中头孢吡肟对胰腺组织的渗透性。目的和方法诱导急性胰腺炎后,单次静脉注射头孢吡肟(0.1 mg/g体重)。在两个不同时间点采集血样和组织标本,进行头孢吡肟浓度测定和微生物学分析。结果轻型急性胰腺炎组和重症急性胰腺炎组给药后30min胰腺组织平均浓度分别为(113±22)mg/kg和(75±22)mg/kg,均显著高于对照组(30±6)mg/kg(p<0.005)。通常从感染胰腺坏死中分离的微生物的最低抑菌浓度(MIC_(90))在0.05至8 mg/L之间,比坏死性胰腺组织中的平均峰值浓度低9至1,500倍。给药后7h 30min,轻症和重症动物的胰腺头孢吡肟浓度仍高于MIC90,分别为100%和83%。经抗生素治疗后胰腺组织感染率明显降低,亚胺培南/西司他丁或头孢吡肟治疗后胰腺组织感染率相似。结论由于头孢吡肟在急性胰腺炎中的抗菌覆盖率和对组织的渗透性,应研究其在重症急性胰腺炎患者中的应用。
Introduction Antibiotic treatment represents a cornerstone in the management of severe acute pancreatitis. However, different antibiotic substances are currently used. In this study, we analyzed penetration of cefepime into pancreatic tissue in two models of acute pancreatitis. Aims and Methodology Following induction of acute pancreatitis, animals were treated with a single intravenous dose of cefepime (0.1 mg/g of body weight). At two different time points, blood and tissue samples were obtained for determination of cefepime concentration and microbiologic analysis. Results Mean pancreatic tissue concentrations ± SEM 30 minutes after drug administration were significantly higher in animals with either mild acute pancreatitis (113 ± 22 mg/kg) or severe acute pancreatitis (75 ± 22 mg/kg) than in control animals (30 ± 6 mg/kg) (p < 0.005). The minimal inhibitory concentrations (MIC90) for organisms usually isolated from infected pancreatic necrosis vary between 0.05 and 8 mg/L, which is between nine and 1,500 times lower than the mean peak concentration found in necrotic pancreatic tissue. Seven hours 30 minutes after antibiotic administration, pancreatic cefepime concentrations were still above the MIC90 in 100% and 83% of animals with mild and severe disease, respectively. The infection rate of pancreatic tissue was significantly lower after antibiotic treatment and was similar after imipenem/cilastatin or cefepime treatment. Conclusion Because of its antibacterial coverage and proven tissue penetration in acute pancreatitis, cefepime should be studied in patients with severe acute pancreatitis.