Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 29;23(1):335.
doi: 10.1186/s13054-019-2613-4.

Biomarkers and clinical scores to identify patient populations at risk of delayed antibiotic administration or intensive care admission

Juan Gonzalez Del Castillo  1   2 , Darius Cameron Wilson  3 , Carlota Clemente-Callejo  1 , Francisco Román  4 , Ignasi Bardés-Robles  5 , Inmaculada Jiménez  4 , Eva Orviz  6 , Macarena Dastis-Arias  7 , Begoña Espinosa  4 , Fernando Tornero-Romero  6 , Jordi Giol-Amich  5 , Veronica González  4 , Ferran Llopis-Roca  5 ; INFURG-SEMES investigators
Collaborators, Affiliations

Biomarkers and clinical scores to identify patient populations at risk of delayed antibiotic administration or intensive care admission

Juan Gonzalez Del Castillo et al. Crit Care. .

Abstract

Background: The performance of blood biomarkers (mid-regional proadrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate) and clinical scores (Sequential Organ Failure Assessment (SOFA), National Early Warning Score (NEWS), and quick SOFA) was compared to identify patient populations at risk of delayed treatment initiation and disease progression after presenting to the emergency department (ED) with a suspected infection.

Methods: A prospective observational study across three EDs. Biomarker and clinical score values were calculated upon presentation and 72 h, and logistic and Cox regression used to assess the strength of association. Primary outcomes comprised of 28-day mortality prediction and delayed antibiotic administration or intensive care (ICU) admission, whilst secondary outcomes identified subsequent disease progression.

Results: Six hundred eighty-four patients were enrolled with hospitalisation, ICU admission, and infection-related 28-day mortality rates of 72.8%, 3.4%, and 4.4%, respectively. MR-proADM and NEWS had the strongest association with hospitalisation and the requirement for antibiotic administration, whereas MR-proADM alone had the strongest association with ICU admission (OR [95% CI]: 5.8 [3.1 - 10.8]) and mortality (HR [95% CI]: 3.8 [2.2 - 6.5]). Patient subgroups with high MR-proADM concentrations (≥ 1.77 nmol/L) and low NEWS (< 5 points) values had significantly higher rates of ICU admission (8.1% vs 1.6%; p < 0.001), hospital readmission (18.9% vs. 5.9%; p < 0.001), infection-related mortality (13.5% vs. 0.2%; p < 0.001), and disease progression (29.7% vs. 4.9%; p < 0.001) than corresponding patients with low MR-proADM concentrations. ICU admission was delayed by 1.5 [0.25 - 5.0] days in patients with high MR-proADM and low NEWS values compared to corresponding patients with high NEWS values, despite similar 28-day mortality rates (13.5% vs. 16.5%). Antibiotics were withheld in 17.4% of patients with high MR-proADM and low NEWS values, with higher subsequent rates of ICU admission (27.3% vs. 4.8%) and infection-related hospital readmission (54.5% vs. 14.3%) compared to those administered antibiotics during ED treatment.

Conclusions: Patients with low severity signs of infection but high MR-proADM concentrations had an increased likelihood of subsequent disease progression, delayed antibiotic administration or ICU admission. Appropriate triage decisions and the rapid use of antibiotics in patients with high MR-proADM concentrations may constitute initial steps in escalating or intensifying early treatment strategies.

Keywords: Disease progression; Emergency department; Infection; Intensive care unit; MR-proADM; NEWS; Sepsis; qSOFA.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Patient enrolment and follow-up process
Fig. 2
Fig. 2
Multivariate logistic regression for all biomarkers and clinical scores for antibiotic administration, hospitalisation, and intensive care (ICU) admission endpoints. CRB-65, severity score for community-acquired pneumonia; CRP, C-reactive protein; MR-proADM, mid-regional proadrenomedullin; NEWS, National Early Warning Score; PCT, procalcitonin; SIRS, systemic inflammatory response syndrome; qSOFA, quick Sequential Organ Failure Assessment; SOFA, Sequential Organ Failure Assessment
Fig. 3
Fig. 3
Kaplan-Meier analysis to identify disease severity subgroups using biomarkers and clinical scores according to MR-proADM (a), PCT (b), lactate (c), NEWS (d), qSOFA (e), and CRB-65 (f) cut-offs. CRB-65, severity score for community-acquired pneumonia; MR-proADM, mid-regional proadrenomedullin; NEWS, National Early Warning Score; qSOFA, quick Sequential Organ Failure Assessment
Fig. 4
Fig. 4
Kaplan-Meier analysis to identify patient populations enriched for disease progression events. Patients were stratified according to a combination of MR-proADM and lactate (a), qSOFA (b), NEWS (c), and CRB-65 (d). CRB-65, severity score for community-acquired pneumonia; MR-proADM, mid-regional proadrenomedullin; NEWS, National Early Warning Score; qSOFA, quick Sequential Organ Failure Assessment
See this image and copyright information in PMC

References

    1. Chen H-C, Lin W-L, Lin C-C, Hsieh W-H, Hsieh C-H, Wu M-H, et al. Outcome of inadequate empirical antibiotic therapy in emergency department patients with community-onset bloodstream infections. J Antimicrob Chemother. 2012;68(4):947–953. doi: 10.1093/jac/dks475. - DOI - PubMed
    1. Chalfin DB, Trzeciak S, Likourezos A, Baumann BM, Dellinger RP. Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit*. Crit Care Med. 2007;35(6):1477–1483. doi: 10.1097/01.CCM.0000266585.74905.5A. - DOI - PubMed
    1. Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R, Furia FF, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department*. Crit Care Med. 2010;38(4):1045–1053. doi: 10.1097/CCM.0b013e3181cc4824. - DOI - PubMed
    1. Saeed K, Wilson DC, Bloos F, Schuetz P, van der Does Y, Melander O, et al. The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study. Crit Care. 2019;23(1):40. doi: 10.1186/s13054-019-2329-5. - DOI - PMC - PubMed
    1. Stalenhoef JE, Nieuwkoop C, Wilson DC, Starre WE, Delfos NM, Leyten EMS, et al. Biomarker guided traige can reduce hospitalisation rate in community acquired febrile urinary tract infection. J Infect. 2018;77(1):18–24. - PubMed

MeSH terms