Stewardship programs that reduce extended-spectrum antibiotics as empiric choice in favor of standard-spectrum agents corresponding to clinical presentation appeared to influence prescribing throughout the period of hospitalization, in the most recent analysis from the INSPIRE trials.1
The reduction in the initial prescribing of extended-spectrum antibiotics, observed lead author Shruti Gohil, MD, MPH, Division of Infectious Diseases, University of California, Irvine School of Medicine, Irvine, "persisted in the postempiric period, confirming clinician tendency to maintain initial therapy choices."1
INSPIRE Trial
The INSPIRE (Intelligent Stewardship Prompts to Improve Real-Time Empiric Antibiotic Selection) trials compare stewardship programs with computerized provider order entry (CPOE) prompts to routine stewardship programs.The prompts guide prescribing toward standard, rather than wide-spectrum agents in the first 3 days of hospitalization before pathogens are identified, for patients with less than 10% risk of multidrug-resistant organisms (MDRO).
The CPOE is part of a stewardship bundle that includes education on the risk estimate calculations, local Pseudomonas or MDRO prevalence, as well as site visits and webinars during the phase-in period. All hospitals, with either the CPOE bundle or routine stewardship, receive educational materials and quarterly coaching calls to encourage optimal antibiotic utilization.
Watch a video interview with the study's primary investigator, Gohil.
The primary measure of the INSPIRE trials was reduced rate of empiric extended-spectrum antibiotic days of therapy. The findings have favored CPOE programs, in separate trials for patients hospitalized for pneumonia, urinary tact infection (UTI), abdominal infection and skin or soft tissue (SST) infection.
The trials with patients with pneumonia and UTI, were conducted across 59 hospitals, with an 18-month baseline period (April 2017 through September 2018) and a 15-month intervention period (April 2019 through June 2020). Ninety-two hospitals were utilized in the trials with patients with abdominal and SST infections, involving 12-month baseline (January 2019-December 2019) and intervention periods (January 2019-December 2019). Patients were of mean (SD) age of 66 (17.8) years, and 44.1% were male.
What You Need to Know
Computerized provider order entry (CPOE) prompts that guide initial empiric prescribing toward standard-spectrum antibiotics led to sustained reductions in extended-spectrum antibiotic use throughout hospitalization.
Across trials involving pneumonia, UTI, abdominal, and skin/soft tissue infections, CPOE hospitals saw 11–23% reductions in postempiric extended-spectrum antibiotic days compared with routine stewardship, with most reductions originating in the first 3 days.
Findings highlight that improving initial antibiotic selection may be more effective than relying on later de-escalation, potentially reducing unnecessary broad-spectrum use for millions of hospitalized patients.
In the latest analysis of data from all 4 trials, comprising 413,901 adult patients hospitalized more than 3 days, 38% to 44% of all antibiotic doses were given during the empiric period. Of the patients receiving extended spectrum antibiotics, 79% to 94% were initiated in the empiric period.
Gohil and colleagues report that, compared with routine stewardship, postempiric (beyond day 3) extended-spectrum days in the CPOE hospitals decreased by 22% (95% CI, 16-28%), 11% (8-15%), 23% (17-27%), and 23% (15-30%) in the pneumonia, UTI, abdominal and SST infection trials, respectively. Of reductions in empiric extended-spectrum antibiotic use, 65 to 84% were maintained through the remainder of hospitalization.
The investigators noted similar reductions for antipseudomonal subsets. Although numerical reduction in vancomycin was observed in all 4 trials, the reduction only reached statistical significance for pneumonia and SST infections.
"These findings suggest that investing in stewardship for initial antibiotic selection, rather than primarily focusing on deescalating antibiotics once started, would reduce unnecessary extended-spectrum antibiotics for millions of patients in US hospitals annually," Gohil and colleagues concluded.
Reference
1.Gohil SK, Septimus E, Kleinman K, et al. Initial antibiotic selection strategy and subsequent antibiotic use—insights from the INSPIRE trials. JAMA 2025; 334:1107-1109.
