111. Increasing Duration of Surgical Prophylaxis Increases Antimicrobial-Associated Adverse Events but Does Not Decrease Surgical Site Infections: An Opportunity for Stewardship

BACKGROUND: The benefits of surgical antimicrobial prophylaxis are limited to the first 24 hours postoperatively. However, little is known about the harms associated with prophylaxis lasting for greater than 24 hours. Thus, we sought to characterize the relationship between duration of prophylaxis and key post-operative outcomes, including surgical site infections (SSI), acute kidney injuries (AKI), and C. difficile infections (CDI) using a large, multi-center national cohort. METHODS: All patients who underwent cardiac, orthopedic total joint, vascular, and colorectal procedures and who received planned manual review by a trained nurse reviewer for type and duration of surgical prophylaxis and for SSI within the national VA healthcare system during the period from FY08 to FY13 were included. The primary exposure variable of interest was duration of postoperative prophylaxis (<24 hours, 24–48 hours, and 48+ hours). Outcomes evaluated included SSI, AKI, and CDI. ORs were calculated using log binomial regression models adjusted for known risk factors for each clinical syndrome selected a priori. RESULTS: Out of a total cohort of 79,092, all patients had SSI and C. difficile outcomes available and 67,729 patients had AKI outcome available. After stratification by type of surgery and adjusting for age, sex, race, diabetes, smoking, pre-operative MRSA colonization status, mupirocin receipt, and type of prophylaxis, there was no significant association between SSI and duration of prophylaxis; longer durations did not lead to additional SSI reduction. Odds of AKI increased with each additional day of prophylaxis among cardiac and noncardiac surgeries. Similarly, the odds of C. difficile increased with each additional day of prophylaxis across all types of surgery (P < 0.01) (see figure). CONCLUSION: Increasing duration of postoperative antimicrobial prophylaxis is associated with higher odds of AKI and C. difficile infection in a dose-dependent manner. Additional days of prophylaxis are not associated with reduced odds of SSI. These findings suggest that stewardship efforts to limit duration have the potential to reduce antimicrobial-associated adverse events without leading to increases in SSI. [Image: see text] DISCLOSURES: K. Itani, sanofi: Grant Investigator, Grant recipient. Pfizer: Grant Investigator, Grant recipient.