From the Department of Anesthesiology, University of California, San Diego School of Medicine, San Diego, California.
Department of Pediatrics, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, California.
Anesth Analg. 2019 May;128(5):935-943. doi: 10.1213/ANE.0000000000003876.
Gram-positive bacteria account for nearly three-quarters of all surgical site infections. Antibiotic prophylaxis against these bacteria with cephalosporins or, in select circumstances, with vancomycin is considered standard of care for prevention of surgical site infections. There is little evidence to describe the optimal dosing regimen for surgical site infection prophylaxis in infants undergoing cardiac surgery, and a great deal of institutional variability exists in dosing prophylactic antibiotics. We designed this study to describe an optimal dose regimen for cephalosporin and vancomycin based on pharmacokinetic evidence for infant open-heart surgery on cardiopulmonary bypass.
Two separate cohorts of infants undergoing cardiac surgery with cardiopulmonary bypass were evaluated. Plasma concentrations of vancomycin (cohort 1, N = 10) and cefazolin (cohort 2, N = 10) were measured, and mixed-effects pharmacokinetic models were constructed for each drug. Simulations of various dosing regimens were performed to describe an appropriate dosing regimen necessary to maintain antibiotic concentrations above the susceptibility cutoff for staphylococci.
Both cefazolin and vancomycin plasma concentration versus time profiles were characterized by a 2-compartment model. Subject weight was a significant covariate for V1 for vancomycin. Subject age was a significant covariate for V1 for cefazolin. Cardiopulmonary bypass did not influence concentration versus time profiles. Simulations demonstrated that a 1-hour vancomycin infusion (15 mg·kg), repeated every 12 hours and a 10-minute infusion of cefazolin (30 mg·kg), repeated every 4 hours maintained plasma concentrations above 4 μg·mL and 16 μg·mL, for vancomycin and cefazolin, respectively. Both concentrations are above the minimum inhibitory concentration 90 for most susceptible staphylococci.
Prophylactic treatment of vancomycin 15 mg·kg infused >1 hour with 12-hour redosing and cefazolin 30 mg·kg infused >10 minutes with 4-hour redosing will maintain serum levels of each antibiotic above the susceptibility cut-offs for susceptible staphylococci in infants undergoing cardiac surgery. Cefazolin levels may be adequate for some, but not all, Gram-negative bacteria. The effect of cardiopulmonary bypass on pharmacokinetics is negligible.
革兰氏阳性菌约占所有手术部位感染的四分之三。用头孢菌素或万古霉素对这些细菌进行抗生素预防被认为是预防手术部位感染的标准护理。目前几乎没有证据可以描述心脏手术患儿中用于预防手术部位感染的头孢菌素和万古霉素的最佳剂量方案，并且在预防性使用抗生素时，机构之间的剂量差异很大。我们设计了这项研究，以根据体外循环婴儿心脏手术的药代动力学证据来描述头孢菌素和万古霉素的最佳剂量方案。
评估了接受体外循环心脏手术的两组婴儿。测量了万古霉素（队列 1，N=10）和头孢唑啉（队列 2，N=10）的血浆浓度，并为每种药物构建了混合效应药代动力学模型。对各种剂量方案进行了模拟，以描述维持抗生素浓度高于葡萄球菌敏感性截止值所需的适当剂量方案。
头孢唑啉和万古霉素的血浆浓度-时间曲线均表现出 2 隔室模型。万古霉素的 V1 与体重呈显著相关。头孢唑啉的 V1 与年龄呈显著相关。体外循环不影响浓度-时间曲线。模拟表明，每 12 小时重复输注 1 小时的万古霉素（15mg·kg）和每 4 小时重复输注 10 分钟的头孢唑啉（30mg·kg），可使万古霉素和头孢唑啉的血浆浓度分别维持在 4μg·mL 和 16μg·mL 以上。两种浓度均高于大多数敏感葡萄球菌的最低抑菌浓度 90。
每 12 小时重复输注 1 小时的万古霉素（15mg·kg）和每 4 小时重复输注 10 分钟的头孢唑啉（30mg·kg）可预防治疗，将维持心脏手术患儿每种抗生素的血清水平高于敏感葡萄球菌的敏感性截止值。头孢唑啉水平可能对某些但不是所有革兰氏阴性菌足够。体外循环对药代动力学的影响可以忽略不计。
