Dataset Information

Interleukin-27 as a candidate diagnostic biomarker for bacterial infection in immunocompromised pediatric patients.

ABSTRACT:

Background

Immunocompromised pediatric patients constitute a growing population that is particularly vulnerable to bacterial infection, necessitating prompt recognition and treatment. This study assessed the utility of interleukin-27 (IL-27) and procalcitonin (PCT) as biomarkers of bacterial infection among immunocompromised pediatric subjects.

Methods

This is a single-center prospective cohort study conducted from July 2016 through September 2017, drawing subjects from the inpatient units at Cincinnati Children's Hospital Medical Center (CCHMC), a large, tertiary care children's hospital. Patients were included if they fit the definition of immunocompromised and were under clinical suspicion for infection, defined by the acquisition of a blood culture at any point during the admission. The primary analysis assessed the accuracy of IL-27 to diagnose bacterial infection in immunocompromised pediatric patients, using PCT as a comparator.

Results

293 patients were recruited, representing 400 episodes of suspected bacterial infection. The median age was 7.8 years (IQR 3.1-13.8 years). Fifty-three percent (n = 213) of the population had a primary oncologic diagnosis, 24% (n = 95) had received a bone marrow transplant, and 21% (n = 85) had received a solid organ transplant. The overall infection rate was 37%, with 70% of those patients having some form of culture positivity. Twenty-eight-day mortality was 5%, 60-day mortality was 9%, with 87% of patients surviving to hospital discharge. The AUC's of the ROC curve to diagnose bacterial infection were 0.62 (0.5-0.68) for IL-27 and 0.65 (0.6-0.73) for PCT. Using the previously determined cutoff of 5.0 ng/mL, the specificity of IL-27 to diagnose bacterial infection reached 94%, with a negative predictive value of 64%.

Conclusions

Despite prior work demonstrating IL-27 and PCT as possible biomarkers of bacterial infection in immunocompromised pediatric patients, we were unable to validate these findings. This illustrates the challenges associated with developing reliable biomarkers of bacterial infection in this vulnerable population.

SUBMITTER: Jacobs L

PROVIDER: S-EPMC6261028 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Interleukin-27 as a candidate diagnostic biomarker for bacterial infection in immunocompromised pediatric patients.

Jacobs Lauren L Berrens Zachary Z Stenson Erin K EK Zackoff Matthew M Danziger-Isakov Lara L Lahni Patrick P Wong Hector R HR

PloS one 20181126 11

<h4>Background</h4>Immunocompromised pediatric patients constitute a growing population that is particularly vulnerable to bacterial infection, necessitating prompt recognition and treatment. This study assessed the utility of interleukin-27 (IL-27) and procalcitonin (PCT) as biomarkers of bacterial infection among immunocompromised pediatric subjects.<h4>Methods</h4>This is a single-center prospective cohort study conducted from July 2016 through September 2017, drawing subjects from the inpati ...[more]

PMID: 30475852

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Project description:Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children.Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis.Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ?5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone.Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27. The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.

Dataset Information

Interleukin-27 as a candidate diagnostic biomarker for bacterial infection in immunocompromised pediatric patients.

Background

Methods

Results

Conclusions

Publications

Interleukin-27 as a candidate diagnostic biomarker for bacterial infection in immunocompromised pediatric patients.

Similar Datasets

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