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.

外科部位感染(SSI)是美国最常见的医疗保健相关感染，影响 每年有16万-30万名患者。在结直肠外科，SSI的发生率和发病率尤其高。 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多 结直肠手术费用(31,933美元比14,608美元)，再入院概率从6.8%增加到27.8%。A2011年 美国外科医师学会对89,148名患者的分析发现，肥胖和病态肥胖会增加患病几率 腹部手术的SSI分别增加了1.8倍和2.5倍，与糖尿病和手术类型无关。 肥胖导致SSI风险的机制尚不清楚。这些可能包括并存的情况， 手术并发症，以及抗菌药物预防的组织渗透率降低。尽管大幅增加了 美国外科患者中肥胖的患病率，当前结直肠手术抗生素预防指南 不包括针对身体大小或成分的量身定做的剂量建议，但增加剂量除外 对于120公斤以上的患者，头孢唑林从2g增加到3g。最近的多项研究清楚地表明，肥胖患者无法实现 并在手术期间维持手术部位的治疗组织浓度。基于解析形态学的应用 医学成像扫描(CT)的高通量分析为了精确量化身体尺寸和成分，我们拥有 确定了预测SSI风险的多个衡量标准。我们还确定了质数的形态度量 患者体内抗生素药代动力学的决定因素。 我们假设，来自医学成像的人体尺寸和成分的形态测量， 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，因此 告知肥胖患者的个性化剂量建议。因此，我们的具体目标是：1)比较 形态测量和标准体型测量作为血浆和手术部位组织浓度的预测因子 术前预防，2)开发基于形态组学和其他识别患者的实用剂量算法 在手术部位达到和维持治疗性抗生素水平的变量，以及3)试验和评估效果 这种基于形态的精确抗生素预防方案在结直肠切除中的应用为大规模的 由手术质量合作伙伴传播。