Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis.

2018

1106-1113

2018 Jul

1530-0293

<p><strong>OBJECTIVES: </strong>Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis.</p>

<p><strong>DESIGN: </strong>Cohort study.</p>

<p><strong>SETTING: </strong>The medical and surgical ICUs at an academic medical center.</p>

<p><strong>SUBJECTS: </strong>We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy.</p>

<p><strong>INTERVENTIONS: </strong>We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve &gt; 0.76 for 14-d and 0.74 for total mortality).</p>

<p><strong>CONCLUSIONS: </strong>Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.</p>

10.1097/CCM.0000000000003137

Crit. Care Med.

29912095

A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study.

2016

2016 May 4

2048-7207

<p><strong>BACKGROUND: </strong>Biomarkers that identify critically ill children with systemic inflammatory response syndrome (SIRS) at low risk for bacterial infection may help clinicians reduce unnecessary antibiotic use.</p>

<p><strong>METHODS: </strong>We conducted a prospective cohort study of children with SIRS and suspected infection admitted to a pediatric intensive care unit from January 5, 2012 to March 7, 2014. We enrolled patients upon initiation of new antibiotics (Time 0) and measured a panel of 8 serum biomarkers daily over 72 hours. Microbiology, imaging, and clinical data were reviewed to classify bacterial infections using Centers for Disease Control and Prevention definitions. We identified cut points of biomarker combinations to maximize the negative predictive value (NPV) and specificity for bacterial infection. Excess antibiotics were calculated as days of therapy beyond day 2 after SIRS onset in patients without bacterial infection.</p>

<p><strong>RESULTS: </strong>Infections were identified in 46 of 85 patients: bacterial (n = 22) and viral (24), whereas 39 patients had no infection identified. At Time 0, C-reactive protein (CRP) &lt;5 mg/dL plus serum amyloid A &lt;15.0 µg/mL had an NPV of 0.92 (95% confidence interval [CI], 0.79-1.0) and specificity of 0.54 (95% CI, 0.42-0.66) to identify patients without bacterial infection, whereas CRP &lt;4 mg/dL plus procalcitonin &lt;1.75 ng/mL had an NPV of 0.90 (95% CI, 0.79-1.0) and specificity of 0.43 (95% CI, 0.30-0.55). Patients without bacterial infection received a mean of 3.8 excess days of therapy.</p>

<p><strong>CONCLUSIONS: </strong>Early measurement of select biomarkers can identify children with SIRS in whom antibiotics might be safely discontinued when there is no other objective evidence of infection at 48 hours.</p>

10.1093/jpids/piw023

J Pediatric Infect Dis Soc

27147715

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

2016

2016 Jan 8

1879-0070

<p>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 9 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 72hours. Forty-two patients (61%) had bacterial sepsis by chart review. A2M concentrations were significantly lower, and PCT concentrations were significantly higher in subjects with bacterial sepsis at 3 of 4 time points. Using optimal cutoff values, the combination of baseline A2M and 72-hour PCT achieved a negative predictive value of 75% (95% confidence interval, 54-96%). The combination of A2M and PCT discriminated bacterial sepsis from other SIRS among SICU patients with suspected sepsis.</p>

10.1016/j.diagmicrobio.2016.01.003

Diagn. Microbiol. Infect. Dis.

26971636

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

2015

6494-500

2015 Oct

1098-6596

<p>Sepsis remains a diagnostic challenge in the intensive care unit (ICU), and the use of biomarkers may help in differentiating bacterial sepsis from other causes of systemic inflammatory syndrome (SIRS). The goal of this study was to assess test characteristics of a number of biomarkers for identifying ICU patients with a very low likelihood of bacterial sepsis. A prospective cohort study was conducted in a medical ICU of a university hospital. Immunocompetent patients with presumed bacterial sepsis were consecutively enrolled from January 2012 to May 2013. Concentrations of nine biomarkers (α-2 macroglobulin, C-reactive protein [CRP], ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) were determined at baseline and at 24 h, 48 h, and 72 h after enrollment. Performance characteristics were calculated for various combinations of biomarkers for discrimination of bacterial sepsis from other causes of SIRS. Seventy patients were included during the study period; 31 (44%) had bacterial sepsis, and 39 (56%) had other causes of SIRS. PCT and CRP values were significantly higher at all measured time points in patients with bacterial sepsis. A number of combinations of PCT and CRP, using various cutoff values and measurement time points, demonstrated high negative predictive values (81.1% to 85.7%) and specificities (63.2% to 79.5%) for diagnosing bacterial sepsis. Combinations of PCT and CRP demonstrated a high ability to discriminate bacterial sepsis from other causes of SIRS in medical ICU patients. Future studies should focus on the use of these algorithms to improve antibiotic use in the ICU setting.</p>

10.1128/AAC.00958-15

Antimicrob. Agents Chemother.

26239984