Biomarker-Guided Antimicrobial optimization to reduce complications from intra-abdominal infections

Project Summary/Abstract Intra-abdominal infections continue to be associated with a complication rate of more than 20%, even for relatively simple cases. In addition, the spread of antimicrobial resistance and the growing number of old or medically unwell patients portends even worse outcomes in the near future. Although technical advances related

to imaging and surgical techniques over the past several decades have expanded therapeutic possibilities, insight into the management of antimicrobials for these conditions has lagged behind. Although prior work by the Surgical Infection Society has led to a shortening of this therapy to generally a fixed duration of five to seven

days, it is biologically implausible that all patients require the exact same duration of therapy. Instead, individualized, precision medicine should result in a better matching of antimicrobial needs with prescription. In order to achieve such an improvement, an accurate biomarker to assess ongoing infection requiring extended

antimicrobial therapy is needed. Serum C-reactive protein (CRP) levels have been shown to be a reliable biomarker for the severity of intra- abdominal infections, and their normalization over time is associated with a successful outcome, while a persistently elevated level is associated with failure and need for further interventions. In addition, serial CRP

measurement is now routinely used to diagnose colorectal surgery-related infections including anastomotic leaks, even before patients become symptomatic. The current proposal is for a planning grant to design and organize a multicenter, randomized, clinical trial to test the hypothesis that clinicians can use serial CRP

measurements to individualize duration of antimicrobial therapy for intra-abdominal infections, and that this strategy will result in a lower global rate of complications. The ultimate U01-funded trial will be administered by the Surgical Infection Society and is projected to include more than 30 enrolling sites with 1958 subjects and

demonstrate a reduction in complication rates from 22% to 17%. The clinical relevance of this effort relates to the significant reduction in morbidity and mortality for a vulnerable, infected population. In addition, more precise antimicrobial management in the future will be associated with a reduction in antimicrobial resistance pressures.