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. 2023 Jun 16;76(12):2047-2055.
doi: 10.1093/cid/ciad101.

Concordance Between Initial Presumptive and Final Adjudicated Diagnoses of Infection Among Patients Meeting Sepsis-3 Criteria in the Emergency Department

Gabriel A Hooper  1 , Carolyn J Klippel  2 , Sierra R McLean  1   3 , Edward A Stenehjem  4 , Brandon J Webb  5 , Emily R Murnin  1   5 , Catherine L Hough  6 , Joseph R Bledsoe  7   8 , Samuel M Brown  2   9 , Ithan D Peltan  2   9
Affiliations

Concordance Between Initial Presumptive and Final Adjudicated Diagnoses of Infection Among Patients Meeting Sepsis-3 Criteria in the Emergency Department

Gabriel A Hooper et al. Clin Infect Dis. .

Abstract

Background: Guidelines emphasize rapid antibiotic treatment for sepsis, but infection presence is often uncertain at initial presentation. We investigated the incidence and drivers of false-positive presumptive infection diagnosis among emergency department (ED) patients meeting Sepsis-3 criteria.

Methods: For a retrospective cohort of patients hospitalized after meeting Sepsis-3 criteria (acute organ failure and suspected infection including blood cultures drawn and intravenous antimicrobials administered) in 1 of 4 EDs from 2013 to 2017, trained reviewers first identified the ED-diagnosed source of infection and adjudicated the presence and source of infection on final assessment. Reviewers subsequently adjudicated final infection probability for a randomly selected 10% subset of subjects. Risk factors for false-positive infection diagnosis and its association with 30-day mortality were evaluated using multivariable regression.

Results: Of 8267 patients meeting Sepsis-3 criteria in the ED, 699 (8.5%) did not have an infection on final adjudication and 1488 (18.0%) patients with confirmed infections had a different source of infection diagnosed in the ED versus final adjudication (ie, initial/final source diagnosis discordance). Among the subset of patients whose final infection probability was adjudicated (n = 812), 79 (9.7%) had only "possible" infection and 77 (9.5%) were not infected. Factors associated with false-positive infection diagnosis included hypothermia, altered mental status, comorbidity burden, and an "unknown infection source" diagnosis in the ED (odds ratio: 6.39; 95% confidence interval: 5.14-7.94). False-positive infection diagnosis was not associated with 30-day mortality.

Conclusions: In this large multihospital study, <20% of ED patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication.

Keywords: misdiagnosis; overtreatment; physician practice variation; sepsis; source diagnosis discordance.

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Conflict of interest statement

Potential conflicts of interest. I. D. P. and S. M. B. have received research support outside the present work from Janssen Pharmaceuticals and the National Institutes of Health (NIH) and funding to their institution from Regeneron and the Centers for Disease Control and Prevention (CDC). S. M. B. has received royalties from Oxford University Press, research support from Sedana Medical and Faron, and payment for data safety monitoring board membership from New York University and Hamilton. E. A. S. reports research support outside the present work from CDC. C. L. H. reports research support outside the present work from NIH and the American Lung Association, support for meeting attendance and travel from Stanford University and the Critical Care Clinical Trials Consortium, and payment for data safety monitoring board membership from the I-SPY-COVID trial consortium. 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.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/concordance-between-initial-presumptive-versus-final-adjudicated-diagnoses-of-infection-among-patients-meeting-sepsis-3-criteria-in-the-emergency-department
Figure 1.
Figure 1.
Patient inclusion flow diagram. Initial medical record review was conducted as part of the parent study and included (1) adjudication of whether the ED clinician suspected infection and the ED-diagnosed source(s) of infection, (2) validation of ED source of infection data by independent adjudication for 30% of patients, and (3) adjudication of the final presence and source of infection. Supplemental medical record review was conducted specifically for the present analysis on a random 10% sample of eligible patients and included (1) validation of the final presence and source of infection adjudication and (2) adjudication of the probability of infection. In addition, a random 21% sample of patients included in supplemental medical record reviews underwent validation of infection probability by independent adjudication. Abbreviation: ED, emergency department.
Figure 2.
Figure 2.
Alluvial diagram illustrating the relationship between the ED-diagnosed source of infection and the presence and source of infection on final adjudication. The “other” category includes less common sources of infection (CNS/meningitis, bloodstream/endocarditis, osteoarticular, etc) and cases with multiple infectious sources. Abbreviations: CNS, central nervous system; ED, emergency department; GI, gastrointestinal.
Figure 3.
Figure 3.
Adjudicated probability of infection according to final source of infection diagnosis (total N = 812). “Unknown” final source of infection was classified as a possible infection. Abbreviation: GI, gastrointestinal.
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Comment in

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