When the paramedics wheeled Mr. L into the Emergency Department, you knew exactly what to do. Low blood pressure: establish good IV access and start fluids. Fever of 102 and left lower quadrant abdominal pain: obtain blood cultures, order antibiotics, and get him to the CT scanner once his vitals stabilize.
In medical school, you think figuring out the diagnosis and deciding what treatment to initiate is the hard part. But as your intern year winds down, you realize that often it’s what comes next that is the gray area of medicine. Making the diagnosis for Mr. L was straightforward: intraabdominal sepsis. The first steps in management were equally clear – antibiotics, a drain for source control, admit. But how long should treatment continue? What comes next?
Decisions about antibiotic duration are often based on expert opinion, rather than on definitive data. In an effort to fill this void, Sawyer and colleagues designed the STOP-IT trial, now published in NEJM, to compare two treatment strategies to determine antibiotic duration: a longer course guided by the patient’s clinical course vs. a shorter, four-day regimen. The data suggest that shorter may be just as effective.In this multi-center, open-label trial, investigators included just over 500 patients with complicated intra-abdominal infections who underwent an intervention to achieve adequate source control. Participants were randomly assigned to one of two arms: to a traditional control group in which treatment was continued for 2 days after resolution of fever and leukocytosis, or to a fixed, four-day course of antibiotics.
The results: the data showed no significant difference in the composite primary endpoint of surgical-site infection, recurrent intra-abdominal infection, or death, which occurred in 22.3% of the control arm as compared with 21.8% of the experimental, short-course group (P=0.92). The median duration of antibiotic therapy, however, was twice as long in the control group: 8 days versus 4 (P<0.001). The trialists had planned to enroll 500 participants per group, but “owing largely to a concern for futility” at an interim analysis, only about half of the originally planned number of participants was included.
NEJM Deputy Editor Lindsey Baden describes the importance of this trial: “The appropriate duration of antimicrobial therapy for intra-abdominal infections has not been established. Now we have some data to suggest that a fixed, shorter course results in similar outcomes with less antibiotic exposure.”
In an accompanying editorial, Drs. Richard Wenzel and Michael Edmond point out that the trial lacks statistical power “to ensure equivalence” – this was a superiority trial, which did not show superiority rather than a non-inferiority trial. Still, they note the many potential benefits of shorter antibiotic courses for the estimated 300,000 people who have complicated intra-abdominal infections in the United States each year: “1.2 million days of antibiotic therapy could be saved….savings nationally could be more than $97 million per year. Reduced antibiotic exposure might also favorably influence the burden of related adverse events.”
To be sure, given the study’s limitations, you are still somewhat in the gray as you decide the duration of antibiotic treatment for Mr. L, but this trial offers new, important data that suggest it may be just as effective to STOP-IT early.
Watch the NEJM Quick Take video summary on antimicrobial therapy for acute intrabdominal infection.