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. 2025 Jul 18;80(6):1197-1207.
doi: 10.1093/cid/ciaf118.

Frequency of Antibiotic Overtreatment and Associated Harms in Patients Presenting With Suspected Sepsis to the Emergency Department: A Retrospective Cohort Study

Claire N Shappell  1 , Tingting Yu  2 , Michael Klompas  2   3 , Anna A Agan  2 , Laura DelloStritto  2 , Brett A Faine  4 , Michael R Filbin  5 , Nicholas M Mohr  4 , Steven T Park  6 , Kamryn Plechot  6 , Emily Porter  5 , David Roach  3 , Sarah E Train  7 , Anne Zepeski  4 , Chanu Rhee  2   3
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Frequency of Antibiotic Overtreatment and Associated Harms in Patients Presenting With Suspected Sepsis to the Emergency Department: A Retrospective Cohort Study

Claire N Shappell et al. Clin Infect Dis. .

Abstract

Background: Treatment guidelines recommend rapidly treating all patients with suspected sepsis with broad-spectrum antibiotics. This may contribute to antibiotic overuse. We quantified the incidence of antibiotic overtreatment and possible antibiotic-associated harms among patients with suspected sepsis.

Methods: We reviewed the medical records of 600 adults treated for suspected sepsis with anti-methicillin-resistant Staphylococcus aureus and/or antipseudomonal β-lactam antibiotics in the emergency departments of 7 hospitals, 2019-2022, to assess their post hoc likelihood of infection, whether narrower antibiotics would have sufficed in retrospect, and possible antibiotic-associated complications. We used generalized estimating equations to assess associations between likelihood of infection and hospital mortality.

Results: Of 600 patients, 411 (68.5%) had definite (48.0%) or probable (20.5%) bacterial infection and 189 (31.5%) had possible but less likely (18.3%) or definitely no (13.2%) bacterial infection. Among patients with definite/probable bacterial infection, 325 of 411 (79.1%) received antibiotics that were overly broad in retrospect. Potential antibiotic-associated complications developed in 104 of 600 (17.3%) patients within 90 days, most commonly new infection or colonization with organisms resistant to first-line agents (48/600 [8.0%]). Mortality was higher for patients with less likely/definitely no bacterial infection versus definite/probable bacterial infections (9.0% vs 4.9%; adjusted odds ratio [aOR], 2.25 [95% confidence interval{CI}, 1.70-2.98]), but antibiotic-associated complication rates were similar (14.8% vs 18.5%; aOR, 0.79 [95% CI, .60-1.05]).

Conclusions: Among 600 patients treated with broad-spectrum antibiotics for possible sepsis, 1 in 3 most likely did not have a bacterial infection, 4 in 5 of those with bacterial infections were treated with regimens that were broader than necessary in retrospect, and 1 in 6 developed antibiotic-associated complications.

Keywords: antibiotics; antimicrobial stewardship; sepsis.

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Conflict of interest statement

Potential conflicts of interest. C. R. and M. K. report royalties from UpToDate. D. R. reports consulting fees from Dynamed and Carb-X, unrelated to this research. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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