Precision Prophylaxis of Surgical Site Infection Utilizing Pharmacomorphomics

利用药形态学精准预防手术部位感染

• 批准号: 10689740
• 负责人: STEWART C WANG
• 金额: $ 46.72万
• 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/10689740
• 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，影响 每年160,000-300,000名患者。 SSI的发病率和发病率在结直肠外科手术中特别好 程序，特别是在合并症肥胖症患者中。 SSI已被证明是均值的两倍以上 结直肠手术的成本（$ 31,933，$ 14,608），并将再入院的可能性从6.8％增加到27.8％。 2011 分析美国外科医生学院的89,148例患者发现肥胖和病态肥胖增加了几率 SSI在腹部程序中的of分别为1.8倍和2.5倍，独立于糖尿病和手术类型。 肥胖驱动SSI风险的机制尚不清楚。这些可能包括合并条件， 手术并发症，抗菌预防的组织渗透减少。尽管大幅增加 美国手术患者的肥胖症患病率，目前的抗生素预防指南 不包括针对体型或成分的定制给药建议，除了增加剂量 120公斤以上的患者头孢唑林的头孢唑素从2g到3g。最近的多项研究清楚地表明，肥胖患者无法实现 并在手术期间保持手术部位的治疗组织浓度。利用基于分析形态学 对医学成像扫描（CTS）的高通量分析，以精确量化身体尺寸和组成，我们有 确定了预测SSI风险的多种措施。我们还确定了主要的形态学措施 患者抗生素药代动力学的决定因素。 我们假设从医学成像中得出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，从而 为肥胖患者提供个性化剂量建议。因此，我们的具体目的是：1）比较 形态学指标符合标准身体大小的度量，作为血浆和手术部位组织浓度的预测指标 术前预防性，2）基于形态学和其他鉴定患者开发一种务实的剂量算法 在手术部位实现和维持治疗抗生素水平的变量，3）驾驶和评估有效性 基于形态学的精确抗生素预防疗法，以准备大规模的大规模准备 通过手术质量合作的传播。