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Randomized Controlled Trial
. 2025 Jul 1;160(7):733-743.
doi: 10.1001/jamasurg.2025.1108.

Improving Empiric Antibiotic Selection for Patients Hospitalized With Abdominal Infection: The INSPIRE 4 Cluster 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 Abdominal Infection: The INSPIRE 4 Cluster Randomized Clinical Trial

Shruti K Gohil et al. JAMA Surg. .

Abstract

Importance: Empiric extended-spectrum antibiotics are routinely prescribed for over a million patients hospitalized annually with abdominal infection despite low likelihoods of infection with multidrug-resistant organisms (MDROs).

Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates can reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with abdominal infection.

Design, setting, and participants: This 92-hospital cluster randomized clinical trial assessed the effect of an antibiotic stewardship bundle with CPOE prompts vs routine stewardship on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults hospitalized with abdominal infection. The trial population included adults (≥18 years) treated with empiric antibiotics for abdominal infection in non-intensive care units (ICUs). The trial periods included a 12-month baseline from January to December 2019 and an intervention period from January to December 2023.

Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients prescribed extended-spectrum antibiotics during the empiric period if the patient's estimated absolute risk of MDRO abdominal infection was less than 10%, coupled with feedback and education.

Main outcomes and measures: The primary outcome was empiric extended-spectrum antibiotic days of therapy. Safety outcomes: days to ICU transfer and hospital length of stay. Analyses compared differences between baseline and intervention periods across strategies.

Results: Among 92 hospitals with 198 480 patients, mean (SD) age was 60 (19) years and 118 723 (59.8%) were female. The trial included 93 476 and 105 004 patients hospitalized with abdominal infection during the baseline and intervention periods, respectively. Receipt of any empiric extended-spectrum antibiotics for the routine care group was 48.2% (22 519 of 46 725) during baseline and 50.5% (27 452 of 54 384) during intervention vs 47.8% (22 367 of 46 751) and 37.6% (19 010 of 50 620) for the CPOE bundle group. The group receiving CPOE prompts had a 35% relative reduction (rate ratio, 0.65; 95% CI, 0.60-0.71; P < .001) in empiric extended-spectrum antibiotic days of therapy vs routine care (raw absolute reduction between baseline and intervention periods was -169 for the CPOE bundle vs -20 for routine care). Hospital length of stay was noninferior to routine care (0.1 days longer during intervention; mean [SD], baseline, 5.4 [3.4] days vs intervention, 5.5 [3.5] days; hazard ratio [HR], 1.02; 90% CI, 0.99-1.06), and mean days to ICU transfer in the CPOE group was indeterminate (both groups 0.2 days longer during intervention; HR, 1.10; 90% CI, 0.99-1.23).

Conclusions and relevance: CPOE prompts recommending empiric standard-spectrum antibiotics (coupled with education and feedback) for patients admitted with abdominal infection who have low risk for MDRO infection significantly reduced extended-spectrum antibiotics without increasing ICU transfers or length of stay.

Trial registration: ClinicalTrials.gov Identifier: NCT05423743.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Gohil reported receiving grants from the National Institute of Allergy and Infectious Diseases (NIAID) during the conduct of the study. Dr Septimus reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Kleinman reported receiving grants from the NIH NIAID during the conduct of the study. Dr Varma reported receiving grants from the NIH NIAID during the conduct of the study. Dr Avery reported receiving grants from the NIH NIAID during the conduct of the study. Dr Mauricio reported receiving grants from the NIH NIAID during the conduct of the study. Dr Sljivo reported receiving grants from the NIH NIAID during the conduct of the study. Dr Nickolay reported receiving grants from NIH NIAID during the conduct of the study. Dr Coady reported receiving grants from the NIH NIAID during the conduct of the study. Dr Meador reported receiving grants from the NIH NIAID (received while working at US Tech Solutions) during the conduct of the study. Dr Froman reported receiving grants from the NIH NIAID during the conduct of the study. Dr Eibensteiner reported receiving grants from the NIH NIAID during the conduct of the study. Dr Kubiak reported receiving grants from the NIH NIAID during the conduct of the study. Dr Platt reported receiving grants from the NIH and having an employer contract with Pfizer, GSK, and Janssen Pharmaceuticals outside the submitted work. Dr Huang reported receiving grants from the NIH, the US Centers for Disease Control and Prevention, the Agency for Healthcare Research and Quality, and Xttrium Laboratories for conducting studies in which participating nursing homes and hospitalized patients receive contributed antiseptic products (the companies had no role in the design, conduct, or analysis of the studies) outside the submitted work. No other disclosures were reported.

Comment on

References

    1. Bonomo RA, Chow AW, Edwards MS, et al. 2024 Clinical practice guideline update by the Infectious Diseases Society of America on complicated intra-abdominal infections: risk assessment, diagnostic imaging, and microbiological evaluation in adults, children, and pregnant people. Clin Infect Dis. 2024;79(suppl 3):S81-S87. doi: 10.1093/cid/ciae346 - DOI - PubMed
    1. Group GBDAC; GBD 2021 Appendicitis Collaborator Group . Trends and levels of the global, regional, and national burden of appendicitis between 1990 and 2021: findings from the Global Burden of Disease Study 2021. Lancet Gastroenterol Hepatol. 2024;9(9):825-858. doi: 10.1016/S2468-1253(24)00157-2 - DOI - PMC - PubMed
    1. Strate LL, Morris AM. Epidemiology, pathophysiology, and treatment of diverticulitis. Gastroenterology. 2019;156(5):1282-1298.e1. doi: 10.1053/j.gastro.2018.12.033 - DOI - PMC - PubMed
    1. Stovall SL, Kaplan JA, Law JK, Flum DR, Simianu VV. Diverticulitis is a population health problem: lessons and gaps in strategies to implement and improve contemporary care. World J Gastrointest Surg. 2023;15(6):1007-1019. doi: 10.4240/wjgs.v15.i6.1007 - DOI - PMC - PubMed
    1. Gallaher JR, Charles A. Acute Cholecystitis: A Review. JAMA. 2022;327(10):965-975. doi: 10.1001/jama.2022.2350 - DOI - PubMed

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