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

Comparison of prior authorization and prospective audit with feedback for antimicrobial stewardship.

2014

1092-9

2014 Sep

1559-6834

<p><strong>OBJECTIVE: </strong>Although prior authorization and prospective audit with feedback are both effective antimicrobial stewardship program (ASP) strategies, the relative impact of these approaches remains unclear. We compared these core ASP strategies at an academic medical center.</p>

<p><strong>DESIGN: </strong>Quasi-experimental study.</p>

<p><strong>METHODS: </strong>We compared antimicrobial use during the 24 months before and after implementation of an ASP strategy change. The ASP used prior authorization alone during the preintervention period, June 2007 through May 2009. In June 2009, many antimicrobials were unrestricted and prospective audit was implemented for cefepime, piperacillin/tazobactam, and vancomycin, marking the start of the postintervention period, July 2009 through June 2011. All adult inpatients who received more than or equal to 1 dose of an antimicrobial were included. The primary end point was antimicrobial consumption in days of therapy per 1,000 patient-days (DOT/1,000-PD). Secondary end points included length of stay (LOS).</p>

<p><strong>RESULTS: </strong>In total, 55,336 patients were included (29,660 preintervention and 25,676 postintervention). During the preintervention period, both total systemic antimicrobial use (-9.75 DOT/1,000-PD per month) and broad-spectrum anti-gram-negative antimicrobial use (-4.00 DOT/1,000-PD) declined. After the introduction of prospective audit with feedback, however, both total antimicrobial use (+9.65 DOT/1,000-PD per month; P &lt; .001) and broad-spectrum anti-gram-negative antimicrobial use (+4.80 DOT/1,000-PD per month; P &lt; .001) increased significantly. Use of cefepime and piperacillin/tazobactam both significantly increased after the intervention (P = .03). Hospital LOS and LOS after first antimicrobial dose also significantly increased after the intervention (P = .016 and .004, respectively).</p>

<p><strong>CONCLUSIONS: </strong>Significant increases in antimicrobial consumption and LOS were observed after the change in ASP strategy.</p>

10.1086/677624

Infect Control Hosp Epidemiol

25111916

Point-of-prescription interventions to improve antimicrobial stewardship.

2015

1252-8

04/2015

1537-6591

<p>Antimicrobial stewardship is pivotal to improving patient outcomes, reducing adverse events, decreasing healthcare costs, and preventing further emergence of antimicrobial resistance. In an era in which antimicrobial resistance is increasing, judicious antimicrobial use is the responsibility of every healthcare provider. Antimicrobial stewardship programs (ASPs) have made headway in improving antimicrobial prescribing using such "top-down" methods as formulary restriction and prospective audit with feedback; however, engagement of prescribers has not been fully explored. Strategies that include frontline prescribers and other unit-based healthcare providers have the potential to expand stewardship, both to augment existing centralized ASPs and to provide alternative approaches to perform stewardship at healthcare facilities with limited resources. This review discusses interventions focusing on antimicrobial prescribing at the point of prescription as well as a pilot project to engage unit-based healthcare providers in antimicrobial stewardship.</p>

10.1093/cid/civ018

Clin. Infect. Dis.

25595748