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Randomized Controlled Trial
. 2025 Jun 1;185(6):680-691.
doi: 10.1001/jamainternmed.2025.0887.

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  1 , Edward Septimus  2 , Ken Kleinman  3 , Neha Varma  4 , Kenneth E Sands  2   5 , Taliser R Avery  2 , Amarah Mauricio  1 , Selsebil Sljivo  4 , Risa Rahm  5 , Kaleb Roemer  5 , William S Cooper  5 , Laura E McLean  5 , Naoise G Nickolay  6 , Russell E Poland  2   5 , Robert A Weinstein  7 , Samir M Fakhry  8 , Jeffrey Guy  5   9 , Julia Moody  5 , Micaela H Coady  4 , Kim N Smith  5 , Brittany Meador  5   6 , Allison Froman  4 , Katyuska Eibensteiner  4 , Mary K Hayden  10 , David W Kubiak  11 , Chenette Burks  5 , L Hayley Burgess  12 , Michael S Calderwood  13 , Jonathan B Perlin  5   14 , Richard Platt  2 , Susan S Huang  1
Affiliations
Randomized Controlled Trial

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 et al. JAMA Intern Med. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Gohil, Septimus, Kleinman, Kubiak, Platt, and Huang and Mss Varma, Avery, Mauricio, Sljivo, Nickolay, Coady, Meador, Froman, and Eibensteiner reported grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health during the conduct of the study. Dr Huang reported grants from the National Institutes of Health during the conduct of the study and conducts clinical studies with support from Xttrium Laboratories outside the submitted work. No other disclosures were reported.

Comment on

References

    1. Stevens DL, Bisno AL, Chambers HF, et al. ; Infectious Diseases Society of America . Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-e52. doi: 10.1093/cid/ciu296 - DOI - PubMed
    1. Edelsberg J, Taneja C, Zervos M, et al. Trends in US hospital admissions for skin and soft tissue infections. Emerg Infect Dis. 2009;15(9):1516-1518. doi: 10.3201/eid1509.081228 - DOI - PMC - PubMed
    1. Miller LG, Eisenberg DF, Liu H, et al. Incidence of skin and soft tissue infections in ambulatory and inpatient settings, 2005-2010. BMC Infect Dis. 2015;15:362. doi: 10.1186/s12879-015-1071-0 - DOI - PMC - PubMed
    1. Vella V, Derreumaux D, Aris E, et al. The incidence of skin and soft tissue infections in the United States and associated healthcare utilization between 2010 and 2020. Open Forum Infect Dis. 2024;11(6):ofae267. doi: 10.1093/ofid/ofae267 - DOI - PMC - PubMed
    1. Kamath RS, Sudhakar D, Gardner JG, Hemmige V, Safar H, Musher DM. Guidelines vs actual management of skin and soft tissue infections in the emergency department. Open Forum Infect Dis. 2018;5(1):ofx188. doi: 10.1093/ofid/ofx188 - DOI - PMC - PubMed

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