STOP-IT

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Sawyer RG, et al. "Trial of short-course antimicrobial therapy for intraabdominal infection". The New England Journal of Medicine. 2015. 372(21):1996-2005.
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Clinical Question

In patients with intra-abdominal infections, does a shorter course of antibiotics (3-5 days) increase the risk of surgical-site infection, recurrent intraabdominal infection, or death within 30 days?

Bottom Line

After source control is achieved, a 3-5 day course of antibiotics was not found to lead to higher rates of surgical-site infection, recurrent intra-abdominal infection, or death as compared with continuing antibiotics until 2 days after resolution of fever, leukocytosis, and ileus.

Major Points

The optimal duration of antibiotics for intraabdominal infections is not known. Traditionally therapy is continued until SIRS markers have resolved (typically 7-14 days), but courses as short as 3-5 days may be equally efficacious and more in keeping with antibiotic stewardship, cost containment, and other goals. Longer duration of antibiotics did not significantly alter rates of surgical-site infection, recurrent intraa-bdominal infection, or death, but did lead to significantly later diagnosis of surgical-site and recurrent intraa-bdominal infection. These sequelae of complicated intraa-bdominal infections may not be decreased but instead be only delayed by longer courses of antimicrobial therapy.

Guidelines

At the time of this writing, the major clinical guidelines such as those from the IDSA had not been updated since this trial was released. However, the most recent IDSA guidelines (2009) do indeed call for a 4-7 day (slightly longer than this study) course of antibiotics unless source control cannot be adequately achieved.

Design

  • Investigator-initiated, open-label, multicenter trial
  • 23 sites in US and Canada
  • 518 patients randomized

Population

Inclusion Criteria

  • Age 16 or older
  • Complicated intra-abdominal infection with either fever (temperature ≥38.0°C), leukocytosis (≥11,000 peripheral white cells per cubic millimeter), or gastrointestinal dysfunction due to peritonitis precluding intake of more than half their normal diet;
  • Intervention carried out to achieve source control (either percutaneously or surgically)

Exclusion Criteria

  • Patients who did not have an adequate source control procedure (not further defined)

Baseline Characteristics

  • Mean age 52.2 years
  • 55.8% male
  • Mean APACHE II scores: 9.9 (control group) and 10.3 (experimental group)
  • Most common origin of infection was colon/rectum followed by appendix and small bowel.
  • 1/3 of infections treated percutaneously (33.1% in control group, 33.3% in experimental group)
  • No significant demographic differences between the two groups

Interventions

  • Randomized patients to receive antimicrobial therapy until 2 days after resolution of physiological abnormalities related to SIRS (control group) vs. 4 days of antimicrobial therapy (experimental group)
  • Did not dictate choice of antimicrobial agents. Appropriateness was determined based on SIS-IDSA guidelines

Outcomes

Comparisons are experimental group vs. control group.

  • Patients were followed for 30 days from the initial source-control procedure

Primary Outcomes

Composite outcome of surgical-site infection, recurrent intra-abdominal infection, and death
21.8% vs. 22.3% (CI for absolute difference -7.0 to 8.0; P = 0.92)
Surgical site infection: 6.6% vs. 8.8% (CI for absolute difference -2.4 to 7.0; P = 0.43)
Recurrent intraabdominal infection: 15.6% vs. 13.8% (CI for absolute difference -4.5 to 7.8; P = 0.67)
Death: 1.2% vs. 0.8% (CI for absolute difference -1.7 to 2.7; P = 0.99)

Secondary Outcomes

Duration of antimicrobial therapy for the index infection

4.0 days vs. 8.0 days (CI -4.7 to -3.3 for the absolute difference; P<0.001)

Antimicrobial-free days at 30 days

25 vs. 21 (p < 0.001)

Rates of subsequent extraabdominal infection

8.9% vs. 5.0% (p = 0.11)

Adherence to the protocol

81.8% vs. 72.7% (p=0.02)

Subgroup Analysis

All of the below subgroup analyses showed no significant effect on the primary composite outcome:

  • APACHE II score of 10 or higher
  • Health care-associated infection
  • Appendiceal vs. non-appendiceal source of index infection
  • Index infection treated by surgical drainage vs. percutaneous drainage

Criticisms

  • Study was discontinued due to funding not being renewed when the first interim analysis showed nearly identical outcomes between the two groups (study had recruited approximately half of intended participants)
  • Few patients with immunosuppression were included
  • Protocol non-adherence was moderately high, although per-protocol and intention-to-treat analyses did not give different results

Funding

  • National Institutes of Health
  • Multiple personal conflicts of interest are reported, including consulting and advisory relationships with pharmaceutical companies

Further Reading