Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial

Abstract

Importance: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed.

Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia.

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 MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020.

Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, 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 and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies.

Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups.

Conclusions and relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged.

Trial registration: ClinicalTrials.gov Identifier: NCT03697070.

Figure 1.. Hospital Recruitment and Randomization in the INSPIRE Pneumonia Trial

MEDITECH is a hospital electronic health record system. CPOE indicates computerized provider order entry; 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 1679 (1019-2319) patients per hospital in the CPOE bundle group and 1544 (1204-1971) 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 days of therapy show sustained reductions in monthly extended-spectrum 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 percentage of patients with pneumonia who received either extended-spectrum only, standard-spectrum only, or a combination of both (mutually exclusive categories) during the empiric period. Percentage of patients receiving standard-spectrum only in the intervention group increased and the percentage receiving extended-spectrum only or combination of both decreased. In both study groups, there was a secular trend showing increased standard-spectrum use after updated national guidance in October 2019.

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 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.