Precision Prophylaxis of Surgical Site Infection Utilizing Pharmacomorphomics

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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.