Any investigator conducting a sepsis trial has to face a fundamental and vexing methodological problem with no simple fix. There is no definitive way to know for sure which subjects actually have the condition. In medical practice, sepsis is a clinical diagnosis based on a constellation of signs and symptoms coupled with a suspicion for infection as the inciting event. But the problem is that sepsis lacks a diagnostic gold standard test.
1Blood cultures growing pathogenic bacteria –the most unimpeachable marker of infection – are positive only in a minority of suspected sepsis patients.
- Cortés-Puch I.
- Hartog C.S.
Opening the debate on the new sepsis definition change is not necessarily progress: revision of the sepsis definition should be based on new scientific insights.
Am J Respir Crit Care Med. 2016; 194: 16-18
2And positive cultures from other sites – such as sputum or urine – cannot reliably distinguish colonization from invasive infection.
- Mellhammar L.
- Kahn F.
- Whitlow C.
- et al.
Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching.
Sci Rep. 2021; 11: 1-12
- Jokinen J.
- Snellman M.
- Palmu A.A.
- et al.
Testing pneumonia vaccines in the elderly: determining a case definition for pneumococcal pneumonia in the absence of a gold standard.
Am J Epidemiol. 2018; 187: 1295-1302
4When it comes to treating patients with suspected sepsis, doctors sacrifice specificity for sensitivity so as not to delay early and potentially life-saving treatment. As a result, many patients are presumptively diagnosed with sepsis who later are determined to have non-infectious conditions.
- Chu C.M.
- Lowder J.L.
Diagnosis and treatment of urinary tract infections across age groups.
Am J Obstet Gynecol. 2018; 219: 40-51
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to The American Journal of the Medical Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Opening the debate on the new sepsis definition change is not necessarily progress: revision of the sepsis definition should be based on new scientific insights.Am J Respir Crit Care Med. 2016; 194: 16-18
- Bacteremic sepsis leads to higher mortality when adjusting for confounders with propensity score matching.Sci Rep. 2021; 11: 1-12
- Testing pneumonia vaccines in the elderly: determining a case definition for pneumococcal pneumonia in the absence of a gold standard.Am J Epidemiol. 2018; 187: 1295-1302
- Diagnosis and treatment of urinary tract infections across age groups.Am J Obstet Gynecol. 2018; 219: 40-51
- Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes.Crit Care. 2016; 20: 89
- Validity of administrative data in recording sepsis: a systematic review.Crit Care. 2015; 19: 139
- Antibiotics for sepsis-finding the equilibrium.JAMA. 2018; 320: 1433-1434
- Retrospective identification of infection in the emergency department: a significant challenge in sepsis clinical trials.Am J Med Sci. 2022; S0002-9629 (Epub ahead of print): 00080-00085https://doi.org/10.1016/j.amjms.2022.02.008
Published online: April 10, 2022
Accepted: April 4, 2022
Received: March 31, 2022
© 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.