Use of a Combination Biomarker Algorithm To Identify Medical Intensive Care Unit Patients with Suspected Sepsis at Very Low Likelihood of Bacterial Infection

Han, Jennifer; Nachamkin, Irving; Coffin, Susan; Gerber, Jeffrey S.; Fuchs, Barry D.; Garrigan, Charles; Han, Xiaoyan; Bilker, Warren B.; Wise, Jacqueleen; Tolomeo, Pam; Lautenbach, Ebbing

doi:10.1128/aac.00958-15

Cited by 33 publications

(36 citation statements)

References 32 publications

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“…We note that in a parallel study of biomarkers to discriminate bacterial sepsis from other SIRS among medical intensive care unit (MICU) patients, CRP proved a useful adjunct to PCT -- but A2M did not discriminate well between bacterial sepsis and other causes of SIRS at any timepoint in the MICU. One hypothesis for the improved discriminatory ability of A2M among SICU patients relative to MICU patients relates to the documented effect of intra-abdominal inflammation upon A2M decline: intra-abdominal sources accounted for few cases of bacterial sepsis in the MICU study, but accounted for 26% of cases in this study (Han et al 2015). …”

Section: Discussionmentioning

confidence: 86%

“…Serum samples for biomarker measurements were obtained from residual blood samples from tests performed for routine clinical care and stored at −70C until testing as previously described (Han et al 2015). Baseline biomarker measurements were performed at the time a patient met all eligibility criteria.…”

Section: Methodsmentioning

confidence: 99%

“…The identification of SICU patients in whom antibacterial therapy can be safely stopped has the potential to aid antibiotic stewardship efforts, avoid adverse drug effects, and combat the evolution of drug-resistant pathogens (Fishman 2006; Dellit et al 2007; Roberts et al 2009; Luyt et al 2014). We designed this study in companion with a study of biomarker performance in MICU patients with suspected sepsis (Han et al 2015), with the hypothesis that optimal biomarker combinations and cutoffs may be specific to the SICU population.…”

Section: Introductionmentioning

confidence: 99%

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Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis

Kelly

Lautenbach

Nachamkin

et al. 2016

Diagnostic Microbiology and Infectious Disease

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Among surgical intensive care unit (SICU) patients, it is difficult to distinguish bacterial sepsis from other causes of systemic inflammatory response syndrome (SIRS). Biomarkers have proven useful to identify the presence of bacterial infection. We enrolled a prospective cohort of 69 SICU patients with suspected sepsis and assayed the concentrations of nine biomarkers (α-2 macroglobulin (A2M), C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin (PCT), serum amyloid A, serum amyloid P, and tissue plasminogen activator) at baseline, 24-, 48-, and 72-hours. 42 patients (61%) had bacterial sepsis by chart review. A2M concentrations were significantly lower and PCT concentrations significantly higher in subjects with bacterial sepsis at three of four timepoints. Using optimal cutoff values, the combination of baseline A2M and 72-hour PCT achieved a negative predictive value of 75% (95% CI, 54%–96%). The combination of A2M and PCT discriminated bacterial sepsis from other SIRS among SICU patients with suspected sepsis.

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Section: Discussionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis

Kelly

Lautenbach

Nachamkin

et al. 2016

Diagnostic Microbiology and Infectious Disease

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“…Although PCT is considered superior to CRP in many studies [20,21], it is not a definitive test for diagnosing sepsis because PCT levels can also be increased in other conditions [22]. PCT, similar to CRP, may be more useful to rule out sepsis than to diagnose it [23][24][25] and the combination of these two biomarkers may improve their ability to exclude sepsis [26]. Studying the time course of these biomarkers may also be helpful to evaluate an individual patient's response to therapy.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Sepsis: Time for a Reappraisal

Pierrakos

Velissaris

Bisdorff

et al. 2020

Preprint

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Introduction: Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.Methods: Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis". There were no restrictions by age or language and all studies, clinical and experimental, were included. Results:We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or C-reactive protein CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. Conclusions:The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular the clinical role of these biomarkers needs to be better evaluated.

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“…CRP and PCT may be more general biomarkers of moderate to severe inflammation, but they could also be useful for informing on the response to treatment (Wacker et al, 2013;Rule et al, 2015). However, the levels of PCT and CRP in combination may be able to discriminate bacterial sepsis from other causes of SIRS (Han et al, 2015).…”

Section: Inflammatory Biomarkersmentioning

confidence: 99%

Could Biomarkers Direct Therapy for the Septic Patient?

Sims

Nguyen

Mayeux

2016

Journal of Pharmacology and Experimental Therapeutics

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Sepsis is a serious medical condition caused by a severe systemic inflammatory response to a bacterial, fungal, or viral infection that most commonly affects neonates and the elderly. Advances in understanding the pathophysiology of sepsis have resulted in guidelines for care that have helped reduce the risk of dying from sepsis for both children and older adults. Still, over the past three decades, a large number of clinical trials have been undertaken to evaluate pharmacological agents for sepsis. Unfortunately, all of these trials have failed, with the use of some agents even shown to be harmful. One key issue in these trials was the heterogeneity of the patient population that participated. What has emerged is the need to target therapeutic interventions to the specific patient's underlying pathophysiological processes, rather than looking for a universal therapy that would be effective in a "typical" septic patient, who does not exist. This review supports the concept that identification of the right biomarkers that can direct therapy and provide timely feedback on its effectiveness will enable critical care physicians to decrease mortality of patients with sepsis and improve the quality of life of survivors.

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Use of a Combination Biomarker Algorithm To Identify Medical Intensive Care Unit Patients with Suspected Sepsis at Very Low Likelihood of Bacterial Infection

Cited by 33 publications

References 32 publications

Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis

Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis

Biomarkers of Sepsis: Time for a Reappraisal

Could Biomarkers Direct Therapy for the Septic Patient?

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