美国外科手术抗菌药物预防使用临床实践指南推荐的一、二代头孢菌素方案预防外科手术部位感染效果研究

Study on Prophylactic Effect of the Regimens of the First-and Second-generation Cephalosporins Recommended by the Clinical Practice Guidelines for Surgical Antimicrobial Prophylaxis from ASHP/IDSA/SIS/SHEA

目的:在目前微生物敏感性水平下,预测美国医院药师学会等学(协)会外科手术抗菌预防临床实践指南推荐的一、二代头孢菌素方案预防标准体质量(以60 kg计)和肥胖(以120 kg计)患者外科手术部位感染(SSI)的效果。方法:以该指南推荐的头孢唑林2 g或3 g q4h和头孢呋辛1.5 g q4h方案分别作为一、二代头孢菌素预防外科SSI的考察方案,以100%f T>MIC(给药间期内游离药物浓度水平位于最低抑菌浓度之上的时间占给药间期的百分率)作为药动学/药效学(PK/PD)靶指数,以金黄色葡萄球菌、凝固酶阴性葡萄球菌和大肠埃希菌为目标菌群,利用蒙特卡罗模拟计算上述方案预防标准体重和肥胖患者外科SSI达到PK/PD靶指数的累积反应分数(CFR),当CFR≥90%时认为抗菌效果佳。结果:对各目标菌群,标准体质量患者使用头孢唑林2 g与头孢呋辛1.5 g均可在给药后4 h内达到≥90%CFR;但对肥胖患者,头孢唑林2 g与3 g以及头孢呋辛1.5 g基本仅在给药后3h内达到≥90%CFR。结论:在目前微生物敏感性水平下,标准体重患者使用头孢唑林2 g q4h和头孢呋辛1.5 g q4h仍可用于外科SSI预防;但对肥胖患者,头孢唑林应采用2 g q3h方案,头孢呋辛应采用1.5 g q3h方案。

Objective: To discuss the efficacy of the regimens,being recommended by the clinical practice guidelines for surgical antimicrobial prophylaxis from the American society of health-system pharmacists (ASHP),of the first-and second-generation cephalosporins for the prevention of surgical site infection under the current microbiological sensitivity level when they were used for the standardweighted and obese patients (calculated by 60 kg and 120 kg,respectively). Methods: Cefazolin and cefuroxime were applied as the objects of the first-and second-generation cephalosporins,respectively. Monte Carlo simulation was used. 100% fT>MIC (i.e.,time during which the unbound drug concentration exceeds the pathogen minimum inhibitory concentration) was used as the PK/PD target index,and S.aureus,Co NS and E.coli were applied as the targeted bacteria. The cumulative fraction of response (CFR) for PK/PD target index achieved within 4 h after the infusion of cefazolin at the dose of 2 or 3 g and cefuroxime at the dose of 1.5 g against the targeted bacteria was calculated by Monte Carlo simulation. The dosing strategy achieving a CFR≥90% was considered effective and optimal. Results: Cefazolin at the dose of 2 g and cefuroxime at the dose of 1.5 g achieved a CFR≥90% up to 4 h after the administration of them against the targeted bacteria for the standard-weighted patients. But for the obese patients,cefazolin displayed a CFR≥90% only within 3 h post-infusion even at the dose of 3 g,and that was the case of cefuroxime at the dose of 1.5 g. Conclusion: Under the current microbiological sensitivity level,the regimens of 2 g/q4 h for cefazolin and 1.5 g/q4 h for cefuroxime can be routinely used for surgical prophylaxis for standard-weighted patients,while the regimens of 2 g/q3 h for cefazolin and 1.5 g/q3 h for cefuroxime should be adopted for obese patients.