Clinical question: Does a short, fixed duration of antibiotic therapy for complicated intraabdominal infections lead to equivalent outcomes and less antibiotic exposure than the traditional approach?
Background: Published guidelines recommend appropriate antimicrobial agents for intraabdominal infections, but the optimal duration of therapy remains unclear. Most practitioners continue to treat for 10-14 days and until all physiologic evidence of the systemic inflammatory response syndrome (SIRS) has resolved. More recently, small studies have suggested that a shorter course may lead to equivalent outcomes with decreased antibiotic exposure.
Study design: Open-label, multicenter, randomized control trial.
Setting: Twenty-three sites throughout the U.S. and Canada.
Synopsis: In the short-course group, 257 patients were randomized to receive antimicrobial therapy for four full days after their index source-control procedure; 260 patients in the control group received antimicrobial therapy until two days after resolution of the physiological abnormalities related to SIRS. The median duration of therapy was 4.0 days (interquartile range [IQR], 4.0-5.0) for the experimental group and 8.0 days (IQR 5.0-10.0) in the control group (95% CI, -4.7 to -3.3; P<0.001).
There was no significant difference in surgical site infection, recurrent intraabdominal infection, or death between the experimental and control groups (21.8% vs. 22.3%, 95% CI -7.0 to 8.0; P=0.92). In the experimental group, 47 patients did not adhere to the protocol, all of whom received a longer antimicrobial treatment course than specified in the protocol.
This trial excluded patients without adequate source control and included a small number of immunocompromised hosts. The rate of nonadherence to the protocol was high, at 18% of patients in the experimental group. The calculated sample size to assert equivalence between groups was not achieved, although the results are suggestive of equivalence.
Bottom line: A shorter course of antimicrobial therapy for complicated intraabdominal infections might lead to equivalent outcomes with less antibiotic exposure compared with current practice; however, it is challenging for providers to stop antimicrobial therapy while patients continue to show physiologic evidence of SIRS.
Citation: Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. NEJM. 2015;372(21):1996-2005.