Zelenitsky S A, Lawson C, Calic D, Ariano R E, Roberts J A, Lipman J, Zhanel G G
College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada Department of Pharmacy, St. Boniface Hospital, Winnipeg, Manitoba, Canada
College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
J Antimicrob Chemother. 2016 Oct;71(10):2902-8. doi: 10.1093/jac/dkw247. Epub 2016 Jul 7.
To use Monte Carlo simulation with an integrated pharmacokinetic-pharmacodynamic (PK-PD) model to evaluate guideline-recommended antimicrobial prophylaxis (AP) regimens with anaerobic coverage in abdominal surgery.
AP regimens were tested in simulated subjects undergoing elective abdominal surgery using relevant PK models and pathogen distributions in surgical site infections (SSIs). Predicted cumulative target attainment was the percentage of simulated subjects with free (unbound) antimicrobial plasma concentrations above the MICs for potential SSI pathogens.
Cefazolin plus metronidazole covered SSI aerobes in 70% and the Bacteroides fragilis group in 99% of subjects, whereas cefoxitin only covered aerobes and anaerobes in 63% and 27% of cases, respectively. The broad-spectrum ceftriaxone plus metronidazole covered aerobes in 82% and anaerobes in 99% of simulations, while ertapenem covered aerobes in 88% and anaerobes in 90% of cases. Clindamycin covered the B. fragilis group in only 11% of cases. For cefazolin, 2 g doses maintained target attainment in simulated subjects from 80 to 120 kg, whereas 1 g doses were associated with lower target attainment against potential Gram-negative pathogens even in those <80 kg. For gentamicin, 3 mg/kg doses were comparable to the suggested 5 mg/kg, but superior to the traditional 1.5 mg/kg.
This study demonstrates the use of PK-PD to inform decisions regarding AP in abdominal surgery. In this case, the findings support avoiding cefoxitin, avoiding clindamycin for anaerobic coverage, selecting 2 g doses of cefazolin even in patients <80 kg and using 3 mg/kg doses of gentamicin.
使用蒙特卡罗模拟结合整合的药代动力学-药效学（PK-PD）模型，评估腹部手术中具有厌氧菌覆盖的指南推荐抗菌预防（AP）方案。
使用相关的PK模型和手术部位感染（SSI）中的病原体分布，在接受择期腹部手术的模拟受试者中测试AP方案。预测的累积目标达成率是指模拟受试者中游离（未结合）抗菌药物血浆浓度高于潜在SSI病原体的最低抑菌浓度（MIC）的百分比。
头孢唑林加甲硝唑在70%的受试者中覆盖了SSI需氧菌，在99%的受试者中覆盖了脆弱拟杆菌群，而头孢西丁仅分别在63%和27%的病例中覆盖了需氧菌和厌氧菌。广谱头孢曲松加甲硝唑在82%的模拟中覆盖了需氧菌，在99%的模拟中覆盖了厌氧菌，而厄他培南在88%的病例中覆盖了需氧菌，在90%的病例中覆盖了厌氧菌。克林霉素仅在11%的病例中覆盖了脆弱拟杆菌群。对于头孢唑林，2 g剂量在80至120 kg的模拟受试者中维持了目标达成率，而1 g剂量即使在体重<80 kg的受试者中，针对潜在革兰氏阴性病原体的目标达成率也较低。对于庆大霉素，3 mg/kg剂量与建议的5 mg/kg相当，但优于传统的1.5 mg/kg。
本研究证明了使用PK-PD为腹部手术中AP的决策提供依据。在这种情况下，研究结果支持避免使用头孢西丁，避免使用克林霉素进行厌氧菌覆盖，即使在体重<80 kg的患者中也选择2 g剂量的头孢唑林，并使用3 mg/kg剂量的庆大霉素。
