Improving Empiric Antibiotic Selection for Patients Hospitalized With Abdominal Infection: The INSPIRE 4 Cluster Randomized Clinical Trial

JAMA Surg. 2025 Jul 1;160(7):733-743. doi: 10.1001/jamasurg.2025.1108.

Abstract

Importance: Empiric extended-spectrum antibiotics are routinely prescribed for over a million patients hospitalized annually with abdominal infection despite low likelihoods of infection with multidrug-resistant organisms (MDROs).

Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates can reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with abdominal infection.

Design, setting, and participants: This 92-hospital cluster randomized clinical trial assessed the effect of an antibiotic stewardship bundle with CPOE prompts vs routine stewardship on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults hospitalized with abdominal infection. The trial population included adults (≥18 years) treated with empiric antibiotics for abdominal infection in non-intensive care units (ICUs). The trial periods included a 12-month baseline from January to December 2019 and an intervention period from January to December 2023.

Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients prescribed extended-spectrum antibiotics during the empiric period if the patient's estimated absolute risk of MDRO abdominal infection was less than 10%, coupled with feedback and education.

Main outcomes and measures: The primary outcome was empiric extended-spectrum antibiotic days of therapy. Safety outcomes: days to ICU transfer and hospital length of stay. Analyses compared differences between baseline and intervention periods across strategies.

Results: Among 92 hospitals with 198 480 patients, mean (SD) age was 60 (19) years and 118 723 (59.8%) were female. The trial included 93 476 and 105 004 patients hospitalized with abdominal infection during the baseline and intervention periods, respectively. Receipt of any empiric extended-spectrum antibiotics for the routine care group was 48.2% (22 519 of 46 725) during baseline and 50.5% (27 452 of 54 384) during intervention vs 47.8% (22 367 of 46 751) and 37.6% (19 010 of 50 620) for the CPOE bundle group. The group receiving CPOE prompts had a 35% relative reduction (rate ratio, 0.65; 95% CI, 0.60-0.71; P < .001) in empiric extended-spectrum antibiotic days of therapy vs routine care (raw absolute reduction between baseline and intervention periods was -169 for the CPOE bundle vs -20 for routine care). Hospital length of stay was noninferior to routine care (0.1 days longer during intervention; mean [SD], baseline, 5.4 [3.4] days vs intervention, 5.5 [3.5] days; hazard ratio [HR], 1.02; 90% CI, 0.99-1.06), and mean days to ICU transfer in the CPOE group was indeterminate (both groups 0.2 days longer during intervention; HR, 1.10; 90% CI, 0.99-1.23).

Conclusions and relevance: CPOE prompts recommending empiric standard-spectrum antibiotics (coupled with education and feedback) for patients admitted with abdominal infection who have low risk for MDRO infection significantly reduced extended-spectrum antibiotics without increasing ICU transfers or length of stay.

Trial registration: ClinicalTrials.gov Identifier: NCT05423743.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents* / therapeutic use
  • Antimicrobial Stewardship* / methods
  • Drug Resistance, Multiple, Bacterial
  • Female
  • Hospitalization
  • Humans
  • Intraabdominal Infections* / drug therapy
  • Male
  • Medical Order Entry Systems*
  • Middle Aged

Substances

  • Anti-Bacterial Agents

Associated data

  • ClinicalTrials.gov/NCT05423743