Original Investigation
Less Is More
April 10, 2025
Improving Empiric Antibiotic Selection for Patients Hospitalized With Skin and Soft Tissue Infection: The INSPIRE 3 Skin and Soft Tissue Randomized Clinical Trial
Shruti K. Gohil, Edward Septimus, Ken Kleinman, et al
JAMA Intern Med. Published online April 10, 2025. doi:10.1001/jamainternmed.2025.0887
Question Can computerized provider order entry (CPOE) prompts with patient-specific risk estimates for multidrug-resistant organisms (MDROs) safely reduce empiric extended-spectrum antibiotic overuse in patients admitted with skin and soft tissue infections (SSTIs)?
Findings In this cluster randomized clinical trial including 92 hospitals and 60 725 noncritically ill adults, CPOE prompts promoting standard-spectrum antibiotics for patients at low risk of MDRO-associated SSTI reduced empiric antibiotics targeting Pseudomonas and MDR gram-negative bacteria by 28%, without increasing intensive care unit transfers or length of stay.
Meaning Real-time CPOE recommendations for standard-spectrum antibiotics using patient-specific risk for MDRO-associated SSTIs substantially and safely decreased empiric extended-spectrum antibiotic overuse in patients hospitalized for SSTI.
Abstract
Importance Empiric extended-spectrum antibiotics are routinely prescribed for patients hospitalized with skin and soft tissue infections (SSTIs) despite low likelihoods of infection with multidrug-resistant organisms (MDROs).
Objective To evaluate whether computerized provider order entry (CPOE) prompts presenting patient-specific and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for noncritically ill patients admitted with SSTI.
Design, Setting, and Participants This cluster randomized clinical trial included 92 hospitals and assessed the effect of an antibiotic stewardship bundle that included CPOE prompts vs routine stewardship on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults hospitalized with SSTI. The trial population included adults 18 years and older treated with empiric antibiotics for SSTI in non–intensive care unit (ICU) settings. Data were collected from January 2019 to December 2023.
Interventions CPOE prompts recommending standard-spectrum antibiotics in patients prescribed extended-spectrum antibiotics during the empiric period when absolute risk of MDRO SSTI was estimated to be less than 10%, coupled with feedback and education.
Main Outcomes and Measures The primary outcome was empiric extended-spectrum antibiotic days of therapy (summed number of different extended-spectrum antibiotics targeting Pseudomonas and/or MDR gram-negative bacteria received per patient each calendar day). The secondary outcome was antipseudomonal days of therapy. Safety outcomes included days to ICU transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies.
Results Among 118 562 patients admitted with SSTI at 92 hospitals, 67 033 (56.7%) were male and the mean (SD) age was 58.0 (17.5) years. A total of 57 837 patients were included in the baseline period and 60 725 in the intervention period. Receipt of any empiric extended-spectrum antibiotic during the baseline and intervention periods was 57.0% (16 855 of 29 595) and 56.0% (17 534 of 31 337), respectively, for the routine stewardship group compared with 55.4% (15 650 of 28 242) and 43.0% (12 647 of 29 388), respectively, for the CPOE group. Empiric extended-spectrum days of therapy per 1000 empiric days targeting Pseudomonas and/or MDR gram-negative pathogens was 511.5 during the baseline period and 488.7 during the intervention period in the routine stewardship group and was 496.2 and 359.1, respectively, in the CPOE bundle group (rate ratio, 0.72; 95% CI, 0.67-0.79; P < .001). There was no evidence of inferiority in the CPOE bundle group for mean (SD) hospital length of stay (routine stewardship, 6.5 [3.8] days; CPOE bundle, 6.4 [3.8] days) and days to ICU transfer (routine stewardship, 6.3 [3.2] days; CPOE bundle, 6.3 [3.1] days).
Conclusions and Relevance In this randomized clinical trial, CPOE prompts recommending standard-spectrum empiric antibiotics for low-risk patients hospitalized with SSTI coupled with education and feedback significantly reduced use of extended-spectrum antibiotics without increasing admissions to ICUs or hospital length of stay.
Trial Registration ClinicalTrials.gov Identifier: NCT05423756
