179. INSPIRE Trial: A 92-Hospital Cluster Randomized Trial of INtelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection versus Routine Antibiotic Selection Practices for Patients with Skin and Soft Tissue Infections
Authors: Gohil Shruti K , Septimus Edward J , Kleinman Ken , Varma Neha , Sands Kenneth E , Mauricio Amarah , Avery Taliser R , Sljivo Selsebil , Rahm Risa , Roemer Kaleb , Cooper William S , McLean Laura E , Nickolay Naoise G , Poland Russell , Weinstein Robert A , Fakhry Samir M , Guy Jeffrey , Moody Julia , Coady Micaela H , Smith Kimberly , Meador Brittany , Froman Allison , Eibensteiner Katyuska , Hayden Mary K , Kubiak David W , Burks Chenette , Burgess L Hayley , Miller Karla , Calderwood Michael S , Perlin Jonathan B , Cuffe Michael , Platt Richard , Huang Susan 
Published: January 2025

Abstract

Background
Up to 40% of hospitalized patients receive extended-spectrum (ES) antibiotics despite low risk of multidrug-resistant organism (MDRO) infection, increasing the risk for adverse effects and future resistance. We evaluated whether computerized physician order entry (CPOE) prompts providing patient-specific MDRO risk estimates could reduce ES antibiotic use compared to routine stewardship practices in patients hospitalized with skin and soft tissue (SST) infections.

Methods
This 92-hospital cluster-randomized trial compared CPOE prompts providing patient-specific absolute risk estimates for MDRO SST infection and recommending standard-spectrum antibiotics for risk &lt; 10% vs. routine stewardship. Trial population: adults treated with antibiotics for SST infection in non-ICUs in the first 3 days of admission (empiric period). Prompts were triggered if ES antibiotics were ordered. Trial periods: 12-month Baseline (Jan 2019-Dec 2019); 5-month Phase-in (Aug 2022–Dec 2022); 12-month Intervention (Jan 2023-Dec 2023). Primary outcome: ES antibiotic days of therapy (ES-DOT) per patient per empiric day; secondary outcome was anti-pseudomonal DOT per empiric day. Unadjusted, as-randomized analyses used (1) generalized linear mixed effects models to assess differences in ES-DOT rates across intervention and baseline periods between groups, clustering by patient, hospital, and period and (2) proportional hazards models to assess safety outcomes: days to ICU transfer and hospital LOS.

Results
We randomized 92 hospitals in 15 states. Across the baseline and intervention periods there were 60,654 and 57,655 non-ICU patients with skin and soft tissue infection in the routine and CPOE prompt groups, respectively. The CPOE prompt group had a 28% reduction in ES-DOT compared to routine care (rate ratio 0.72 [95% CI 0.67-0.79], p&lt; 0.001). Anti-pseudomonal DOT was reduced by 28% (Table, Figure 1) without significant differences in LOS or ICU transfers.

Conclusion
INSPIRE CPOE prompts providing patient-specific MDRO risk estimates recommending standard spectrum antibiotics in low risk patients significantly reduced empiric ES prescribing in adults admitted with skin and soft tissue infection.

Disclosures
Ken Kleinman, ScD, Xttrium Laboratories: Conducting studies in which participating hospital patients received contributed antiseptic products outside the submitted work Richard Platt, MD, MSc, GlaxoSmithKline: Contract to academic department|Janssen: Contract to academic department|Pfizer: Contract to academic department Susan Huang, MD, MPH, Xttrium Laboratories: Conducting studies in which participating hospital patients received contributed antiseptic products outside the submitted work