Trial of short-course antimicrobial therapy for intraabdominal infection

Abstract

Background: The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear.

Methods: We randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections.

Results: Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, -0.5 percentage point; 95% confidence interval [CI], -7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, -4.0 days; 95% CI, -4.7 to -3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes.

Conclusions: In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.).

Conflict of interest statement

No other potential conflict of interest relevant to this article was reported.

Figures

Figure 1. Enrollment, Randomization, and Treatment

All enrolled patients had complicated intraabdominal infection and adequate source control. The control group consisted of patients who received antibiotics until 2 days after resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy, and the experimental group received a fixed course of antibiotics for 4±1 calendar days.

Figure 2. Kaplan–Meier Time-to-Event Curves for the Composite Primary Outcome, According to Treatment Group

The composite primary outcome was surgical-site infection, recurrent intraabdominal infection, or death.

Figure 3. Primary Composite Outcome in Key Subgroups

The median proportions of patients with the composite outcome are shown. I bars indicate the interquartile range.