Precision Prophylaxis of Surgical Site Infection Utilizing Pharmacomorphomics

利用药效组学精准预防手术部位感染

• 批准号: 10238796
• 负责人: STEWART C WANG
• 金额: $ 46.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10238796
• 关键词: Precision; Prophylaxis; Surgical; Site; Infection

Surgical site infection (SSI) is the most common healthcare-associated infection in the United States, impacting 160,000-300,000 patients each year. The incidence and morbidity of SSI are particularly great in colorectal surgical procedures, especially among patients with comorbid obesity. SSI has been demonstrated to more than double the mean cost of colorectal surgery ($31,933 vs $14,608) and increase the probability of readmission from 6.8% to 27.8%. A 2011 analysis of 89,148 patients by the American College of Surgeons found that obesity and morbid obesity increased the odds of SSI in abdominal procedures by 1.8- and 2.5-fold, respectively, independent of diabetes and procedure type. The mechanisms by which obesity drives SSI risk remains unclear. These may include comorbid conditions, operative complications, and reduced tissue penetration of antimicrobial prophylaxis. Despite the profound increase in the prevalence of obesity among surgical patients in the US, current antibiotic prophylaxis guidelines for colorectal surgery do not include tailored dosing recommendations for body size or composition, with the exception of increasing the dosing of cefazolin from 2g to 3g for patients over 120 kg. Multiple recent studies clearly show that obese patients fail to achieve and maintain therapeutic tissue concentrations at operative sites during surgery. Utilizing analytic morphomics based on high-throughput analysis of medical imaging scans (CTs) to precisely quantify body dimensions and composition, we have identified multiple measures that predict SSI risk. We have also identified morphomic measures that are prime determinants of antibiotic pharmacokinetics in patients. We hypothesize that morphomic measures of body dimension and composition, derived from medical imaging, can most accurately predict plasma and tissue drug concentrations of perioperative prophylactic antibiotics, and thus inform personalized dosing recommendations for obese patients. Our specific aims are therefore to: 1) Compare morphomic metrics to standard body-size measures as predictors of plasma and surgical site tissue concentrations of preoperative prophylactic, 2) Develop a pragmatic dosing algorithm based on morphomics and other identified patient variables to achieve and maintain therapeutic antibiotic levels at surgical sites, and 3) Pilot and evaluate the effectiveness of this morphomic-based precision antibiotic prophylaxis regimen for colorectal resections in preparation for large-scale dissemination by surgical quality collaboratives.

手术部位感染（SSI）是美国最常见的医疗保健相关感染， 每年16 - 30万患者。SSI的发生率和发病率在结直肠外科尤其高 手术，特别是在患有肥胖症的患者中。SSI已被证明是平均值的两倍以上 结直肠手术费用（31，933美元对14，608美元），并将再入院概率从6.8%增加到27.8%。2011年的一项 美国外科医生学会对89,148名患者进行的分析发现，肥胖和病态肥胖增加了 腹部手术中SSI的发生率分别为1.8倍和2.5倍，与糖尿病和手术类型无关。 肥胖驱动SSI风险的机制仍不清楚。这些可能包括合并症， 手术并发症和减少抗菌预防的组织渗透。尽管在这一领域， 美国外科手术患者中肥胖的患病率，结直肠手术的当前抗生素预防指南 不包括针对体型或组成的量身定制的给药建议，但增加剂量除外 对于体重超过120 kg的患者，头孢唑林从2 g增加到3 g。最近的多项研究清楚地表明，肥胖患者无法实现 并在手术过程中在手术部位保持治疗组织浓度。利用分析形态学， 高通量分析医学成像扫描（CT），以精确量化身体尺寸和组成，我们有 确定了预测SSI风险的多个指标。我们还确定了主要的形态学措施， 患者体内抗生素药代动力学的决定因素 我们假设，从医学成像中获得的身体尺寸和组成的形态学测量， 可以最准确地预测围手术期预防性抗生素的血浆和组织药物浓度， 为肥胖患者提供个性化的给药建议。因此，我们的具体目标是：1）比较 形态学指标与标准体型测量作为血浆和手术部位组织中 术前预防，2）基于形态学和其他确定的患者，开发实用的给药算法 在手术部位达到和维持治疗性抗生素水平的变量，以及3）试验和评估有效性 这种基于形态学的精确抗生素预防方案用于结直肠切除术， 由外科质量合作者传播。