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

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 patientand 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 198480 patients, mean (SD) age was 60 (19) years and 118723 (59.8%) were female. The trial included 93476 and 105004 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 46725) during baseline and 50.5% (27452 of 54384) during intervention vs 47.8% (22 367 of 46751) and 37.6% (19 010 of 50620) 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.