Original Investigation
April 10, 2025
Improving Empiric Antibiotic Selection for Patients Hospitalized With Abdominal Infection: The INSPIRE 4 Cluster Randomized Clinical Trial
Shruti K. Gohil, Edward Septimus, Ken Kleinman, et al
JAMA Surg. Published online April 10, 2025. doi:10.1001/jamasurg.2025.1108
Question Can computerized provider order entry (CPOE) prompts with patient-specific risk estimates for multidrug-resistant organisms (MDROs) safely reduce empiric extended-spectrum antibiotics in patients hospitalized with abdominal infections?
Findings In a 92-hospital cluster randomized clinical trial including 105 004 non–critically ill adults, CPOE prompts (plus education and feedback) promoting standard-spectrum antibiotics in patients with low MDRO-infection risk had a 35% relative reduction in empiric extended-spectrum antibiotic days of therapy, without evidence of inferiority in intensive care unit transfers or length of stay.
Meaning Results suggest that CPOE-generated recommendations for standard-spectrum antibiotics using patient-specific risk for MDRO-associated abdominal infections substantially and safely reduced empiric extended-spectrum antibiotics in patients hospitalized for abdominal infection.
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
