Intra-abdominal Infection: Short-Course Antibiotics Effective

Troy Brown, RN

May 21, 2015

For patients with complicated intra-abdominal infections and adequate source control, an antibiotic course of about 4 days was as effective as an antibiotic course of up to 10 days, according to a randomized controlled trial.

Robert G. Sawyer, MD, from the Department of Surgery, University of Virginia Health System, Charlottesville, and colleagues present their findings in an article published in the May 21 issue of the New England Journal of Medicine.

Complicated intra-abdominal infection is a common problem globally, with about 300,000 cases of appendicitis each year with the United States and at least twice as many cases of nonappendiceal infection requiring treatment, the authors write.

"Despite the diversity of specific processes in these infections, the basic tenets of management are similar: resuscitate patients who have the systemic inflammatory response syndrome (SIRS), control the source of contamination, remove most of the infected or necrotic material, and administer antimicrobial agents to eradicate residual pathogens," the authors explain.

The appropriate duration of antimicrobial treatment remains unclear, however.

Therefore, the researchers randomly assigned 518 patients with complicated intra-abdominal infection and adequate source control to either the experimental group (n = 257) or the control group (n = 260). Patients in the experimental group received a fixed course of antibiotics for 4 ± 1 calendar days, and patients in the control group received the antibiotics until 2 days after fever, leucocytosis, and ileus resolved, for a maximum of 10 days of therapy.

The researchers found no difference in the study's primary outcome, which was a composite of infection at the surgical site, recurrent intra-abdominal infection, or death within 30 days after the index source-control procedure. Specifically, 56 (21.8%) patients in the experimental group developed complications including surgical site infection, recurrent intra-abdominal infection, or death, compared with 58 (22.3%) patients in the control group (absolute difference, −0.5 percentage point; 95% confidence interval [CI], −7.0 to 8.0; P = .92).

Patients in the experimental group underwent antibiotic therapy for a mean duration of 4.0 days (interquartile range, 4.0 - 5.0 days) compared with 8.0 days (interquartile range, 5.0 - 10.0 days) in the control group (absolute difference, −4.0 days; 95% CI, −4.7 to −3.3; P < .001).

There was no difference in rates of secondary infections with resistant pathogens, extra-abdominal infection, or Clostridium difficile infection between the groups.

The authors note that 47 patients in the experimental group received treatment that extended beyond the specified protocol duration. Of those, 16 had continued elevated white-cell count and two had persistent fever.

"[O]utcomes in patients with intra-abdominal infections who have undergone a successful source-control procedure and receive a fixed, 4-day course of antimicrobial therapy appear to be generally similar to outcomes in patients in whom systemic antimicrobial agents are administered until after the resolution of signs and symptoms of sepsis," the authors conclude.

"A nagging question is why more than 20% of the patients in both groups had complications after treatment," write Richard P. Wenzel, MD, from the Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, and Michael B. Edmond, MD, MPH, from the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, in an accompanying editorial. "Early in the 21st century, it seems likely that source control remains a considerable problem in treating abdominal sepsis. Nevertheless, a contrarian might argue that patients in both study groups needed more, not fewer, days of antibiotics. However, to support the latter argument, we would have expected still more complications after treatment in the short-course therapy group. In the future, there may be improved approaches to source control in abdominal sepsis and safer antibiotics for limiting microbial growth. In the meantime, we have encouraging data from the… trial that suggest cost savings and improved safety."

The study was funded by the National Institutes of Health. The authors report a variety of relationships with various pharmaceutical companies. Full conflict-of-interest information is available on the journal's website. Dr Wenzel reports receiving personal fees from Otho, Op-Gen, Cubist, and Shionogi and personal fees, nonfinancial support, and other support from 3M outside the submitted work. Dr Edmond has disclosed no relevant financial relationships.

N Engl J Med. 2015;372:1996-2005, 2062-2063. Article full text, Editorial full text


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