Burns Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Antimicrob Agents Chemother. 2011 Nov;55(11):5238-42. doi: 10.1128/AAC.05033-11. Epub 2011 Aug 22.
Surgical site infections are common, so effective antibiotic concentrations at the sites of infection, i.e., in the interstitial fluid (ISF), are required. The aim of this study was to evaluate contemporary perioperative prophylactic dosing of cefazolin by determining plasma and subcutaneous ISF concentrations in patients undergoing elective/semielective abdominal aortic aneurysm (AAA) open repair surgery. This was a prospective pharmacokinetic study in a tertiary referral hospital. Cefazolin (2 g) was administered as a 3-min slow bolus 30 min prior to incision in 12 enrolled patients undergoing elective/semielective AAA open repair surgery. Serial blood, urine, and ISF (via microdialysis) samples were collected and analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Cardiac output was determined using pulse waveform contours with Vigileo. The recruited patients had a median (interquartile range) age of 70 (66 to 76) years and weight of 88 (81 to 95) kg. The median (interquartile range) terminal volume of distribution was 0.14 (0.11 to 0.15) liter/kg, total clearance was 0.05 (0.03 to 0.06) liter/h, and minimum observed unbound concentration was 5.7 (5.4 to 8.1) mg/liter. The penetration of unbound drug from plasma to ISF was 85% (78% to 106%). We found correlations present, albeit weak, between cefazolin clearance and cardiac output (r(2) = 0.11) and urinary creatinine clearance (r(2) = 0.12). In conclusion, we found that a single 2-g dose of cefazolin administered 30 min before incision provides plasma and ISF concentrations in excess of the likely MICs for susceptible pathogens in patients undergoing AAA open repair surgery.
手术部位感染很常见，因此需要在感染部位（即间质液 [ISF]）达到有效的抗生素浓度。本研究旨在通过评估接受择期/半择期腹主动脉瘤 (AAA) 开放修复手术患者的头孢唑林围手术期预防性给药剂量，来确定其当前的使用剂量。这是在一家三级转诊医院进行的前瞻性药代动力学研究。在 12 名接受择期/半择期 AAA 开放修复手术的患者中，在切开前 30 分钟，给予头孢唑林（2 g）静脉缓慢推注，推注时间为 3 分钟。采集并使用经过验证的液相色谱-串联质谱法（LC-MS/MS）分析了一系列血、尿和 ISF（通过微透析）样本。使用脉搏波形轮廓法（Vigileo）确定心输出量。招募的患者的中位（四分位间距）年龄为 70（66 至 76）岁，体重为 88（81 至 95）kg。中位（四分位间距）末端分布体积为 0.14（0.11 至 0.15）升/千克，总清除率为 0.05（0.03 至 0.06）升/小时，最低观察到的未结合浓度为 5.7（5.4 至 8.1）mg/升。未结合药物从血浆到 ISF 的穿透率为 85%（78% 至 106%）。我们发现，头孢唑林清除率与心输出量（r(2) = 0.11）和尿肌酐清除率（r(2) = 0.12）之间存在相关性，尽管相关性较弱。总之，我们发现，接受 AAA 开放修复手术的患者在切开前 30 分钟给予单次 2 g 剂量的头孢唑林，可提供超过易感病原体可能 MIC 的血浆和 ISF 浓度。
