Original Investigation 

Infectious Diseases

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

Shruti K. Gohil, Taliser R. Avery, Ken Kleinman, et al

JAMA Netw Open 2026;9;(6):e2616611. doi:10.1001/jamanetworkopen.2026.16611

Key Points

Question  Can computerized provider order entry (CPOE) prompts with patient-specific risk estimates for multidrug-resistant organisms (MDROs) safely reduce the use of empiric extended-spectrum antibiotics in patients with cancer hospitalized with infection?

Findings  This secondary analysis of 4 cluster randomized clinical trials evaluating CPOE prompts (plus education and feedback) promoting standard-spectrum antibiotics in patients with low MDRO infection risk found that empiric extended-spectrum antibiotic days of therapy decreased by 17% to 27%, without evidence of inferiority in intensive care unit transfers or length of stay.

Meaning  This study’s results suggest that CPOE-generated recommendations based on patient-specific risk for MDRO-associated pneumonia, urinary tract infections, skin or soft tissue infection, and abdominal infections may substantially and safely reduce the use of empiric extended-spectrum antibiotics in patients with cancer hospitalized for infection.

Abstract

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