Improving Empiric Antibiotic Selection for Patients With Cancer Hospitalized With Infection: Secondary Analysis of the INSPIRE Cluster Randomized Trials.

Importance: Patients with cancer are routinely prescribed extended-spectrum antibiotics despite overall low multidrug-resistant organism (MDRO) prevalence. Evidence for effective strategies to reduce antibiotic overuse in this population is limited. Objective: To evaluate the association of computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates with empiric extended-spectrum antibiotic use in patients with cancer. Design, Setting, and Participants: This secondary analysis of the 4 Intelligent Stewardship Prompts to Improve Real-Time Empiric Antibiotic Selection (INSPIRE) cluster randomized clinical trials identified non-critically ill hospitalized adults (aged ≥18 years) with discharge diagnosis codes for hematologic or solid organ malignant tumors in the INSPIRE pneumonia, urinary tract infection (UTI), abdominal, and skin and soft tissue infection (SSTI) trials. Intervention: Each trial evaluated the effect of CPOE prompts that used real-time patient-specific electronic health record data to estimate MDRO infection risk for patients prescribed extended-spectrum antibiotics during the first 3 hospital days; the prompt recommended standard-spectrum antibiotics when the risk of antibiotic-resistant infection was less than 10%. Main Outcomes and Measures: Extended-spectrum antibiotic days of therapy were evaluated using as-randomized, adjusted difference-in-difference analyses with generalized linear mixed-effects models and clustering by patient, hospital, and period. Days to intensive care unit transfer, hospital length of stay, hospital readmissions, and in-hospital mortality were also assessed. Results: In all trials, 36 861 patients (mean [SD] age, 69.0 [13.6] years; 19 076 [52%] female), including 18 272 baseline and 18 589 intervention patients, had cancer. Extended-spectrum antibiotic days of therapy decreased by 27% (rate ratio [RR], 0.73; 95% CI, 0.67-0.80; P < .001) in the pneumonia trial, 24% (RR, 0.76; 95% CI, 0.68-0.84; P < .001) in the UTI trial, 17% (RR, 0.83; 95% CI, 0.74-0.92; P < .001) in the SSTI trial, and 24% (RR, 0.76; 95% CI, 0.69-0.84; P < .001) in the abdominal infection trial. Pre-post changes in hospital length of stay, intensive care unit transfers, readmissions, and in-hospital mortality were similar in the 2 groups. Conclusions and Relevance: In this secondary analysis of randomized clinical trials, an antibiotic stewardship bundle that included CPOE prompts recommending standard-spectrum antibiotics for patients at low risk for antimicrobial-resistant infections was associated with reduced extended-spectrum antibiotic use in non-critically ill patients with cancer who were hospitalized with community-acquired pneumonia, UTI, SSTI, or abdominal infection, without observed differences in safety outcomes. The findings support scalable, low-burden strategies to improve antimicrobial use in patients with cancer, a population with limited evidence to guide stewardship. Trial Registration: ClinicalTrials.gov Identifiers: NCT05423756, NCT05423743, NCT03697070, NCT03697096.