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

• Published in: PloS one 2018-11, Vol.13 (11), p.e0207620-e0207620
• Main Authors: Jacobs, Lauren, Berrens, Zachary, Stenson, Erin K, Zackoff, Matthew, Danziger-Isakov, Lara, Lahni, Patrick, Wong, Hector R
• Format: Article
• Language: English
• Subjects: Bacteria; Bacterial diseases; Bacterial infections; Biology and Life Sciences; Biomarkers; Blood culture; Bone marrow; Bone marrow transplantation; Children; Critical care; Cytokines; Diagnostic systems; Drug resistance; Health care facilities; Hospitals; Infections; Interleukin 27; Laboratories; Lymphoma; Medical diagnosis; Medical records; Medicine and Health Sciences; Mortality; Patients; Pediatrics; Procalcitonin; Review boards; Sepsis; Stem cell transplantation; Systematic review; Transplants & implants; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0207620

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. 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. 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%. 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.