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

Gohil, Shruti K; Avery, Taliser R; Kleinman, Ken; Septimus, Edward; Mauricio, Amarah; Sands, Kenneth E; Varma, Neha; Sljivo, Selsebil et al. · JAMA Netw Open · 2026

rct · Level II

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Abstract

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. 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. 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. 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%. 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. 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. 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. ClinicalTrials.gov Identifiers: NCT05423756, NCT05423743, NCT03697070, NCT03697096.