O02 - The SIS Study To Optimize Peritoneal Infection Therapy (STOP-IT) Trial: Four Days of Antibiotics Result in Similar Outcomes Compared to Duration Based on Resolution of Physiological Response
Author(s):
Robert Sawyer, Jeffrey Claridge, Avery Nathens, Therese Duane, Heather Evans, Charles Cook, Patrick O'Neill, John Mazuski, Reza Askari, Mark Wilson, Lena Napolitano, Nicholas Namias, Preston Miller, E. Patchen Dellinger, Christopher Watson, Raul Coimbra, Daniel Dent, Stephen Lowry, Michael Moncure, Christine Cocanour, Michael West, Kasey Banton, William Flynn, Pamela Lipsett, Kimberley Popovsky, University of Virginia
Background: After source control, antibiotics are required to clear pathogens from the peritoneum. The most effective duration of antimicrobial therapy in this setting is unclear.
Hypothesis: The administration of four days of antibiotics after source control leads to outcomes equivalent to a strategy where antibiotics are administered for two days beyond resolution of physiologic abnormalities.
Methods: The trial was a 23-center, randomized, controlled study of four days of antibiotics after source control (4 day) versus antibiotics given for two days beyond resolution of fever (T ≥ 38), leukocytosis (WBC ≥11), and ileus, with a maximum of 10 days (clinical response- CR). Antibiotic regimens adhered to SIS guidelines. The primary outcome was a composite of surgical site infection, recurrent intraabdominal infection, and death within 30 days per group allocation (intent-to-treat). Secondary outcomes included rates of extra-abdominal infection and subsequent infections with resistant pathogens, including C. difficile.
Results: 521 patients were enrolled: 263 in the CR group and 258 in the 4 day group. Colon/rectum was the most common source (159), followed by appendix (70), and small bowel (69). APACHE II was similar between groups: CR=9.8±0.4 (SEM), 4 day=10.1±0.4. Median duration of antibiotics with interquartile range (IQR) was 8 (5-10) days in the CR group and 4 (4-5) days in the 4 day group (p<0.01 by Mann-Whitney U test). There was no difference in the composite or component endpoints. No difference was found in rates of subsequent infection with resistant pathogens or C. difficile. There were fewer patients with extra-abdominal infections (principally urinary tract infections) in the CR day group than the 4 day group (17/263=6.5% versus 31/258=12%, p=0.028 by Pearson χ2 test).
Conclusions: Four days of antibiotics to treat intraabdominal infections after source control yields outcomes similar to a longer course based on resolution of physiologic abnormalities and is associated with significantly fewer days of antibiotic exposure. We recommend this approach as standard of care.