Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial

Abstract

Importance: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed.

Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI.

Design, setting, and participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020).

Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education.

Main outcomes and measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods.

Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively.

Conclusions and relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers.

Trial registration: ClinicalTrials.gov Identifier: NCT03697096.

Figure 1.. Hospital Recruitment and Randomization in the INSPIRE Urinary Tract Infection Trial

MEDITECH is a hospital electronic health record system. CPOE indicates computerized provider order entry and INSPIRE, Intelligent Stewardship Prompts to Improve Real-time Empiric antibiotic selection. ^aAll analyses are as-randomized because all hospitals remained in the trial until end of intervention (no hospital withdrawals after enrollment). There was a median (IQR) of 2364 (1277-2963) patients per hospital in the CPOE bundle group and 2008 (1365-3064) in the routine stewardship group.

Figure 2.. Monthly Empiric Extended- and Standard-Spectrum Antibiotic Days of Therapy in the Computerized Provider Order Entry (CPOE) Bundle vs Routine Stewardship Across the Baseline and Intervention Periods

Panel A, Temporal trends in empiric (hospital days 1-3) extended- and standard-spectrum antibiotic days of therapy show sustained reductions in monthly extended-spectrum antibiotic and increases in standard-spectrum antibiotic days of therapy in the intervention group that was evident early in the phase-in period. Effects persisted despite arrival of the COVID-19 pandemic. Panel B, Temporal trends in the percentage of patients with urinary tract infection who received either extended-spectrum antibiotics only, standard-spectrum antibiotics only, or a combination of both (mutually exclusive categories) during the empiric period. The percentage of patients receiving standard-spectrum antibiotics only in the intervention group increased, while the percentage receiving extended-spectrum antibiotics only or combination of both decreased.

Figure 3.. Effect of Computerized Provider Order Entry (CPOE) Bundle Intervention vs Routine Stewardship on Trial Effectiveness and Safety Outcomes

Panel A, Shown are group-specific relative rate ratios of intervention to baseline periods (indicated by horizontal lines) for the primary and secondary outcomes. Results are based on unadjusted generalized linear mixed-effects models that accounted for clustering within hospitals and period. Bubble plots of raw rate ratios (predicted random effects or exponentiated frailties) from individual hospitals relative to their group effects are shown. The area of the bubble indicates the relative number of patients contributing data to the trial. Panel B, Shown are group-specific hazard ratios of intervention to baseline periods (indicated by horizontal lines) for safety outcomes. Results are based on proportional hazards models that accounted for clustering within hospitals and period. Bubble plots of raw hazard ratios (predicted random effects or exponentiated frailties) from individual hospitals relative to their group effects are shown. The area of the bubble indicates the relative number of patients contributing data to the trial.