Diagnosing IFD in pediatric patients is challenging: cultures are often negative and diagnostic efficacy of biomarkers such as β-D-glucan assay (BG) and galactomannan assay (GM) is unclear. The 2017 International Pediatric Fever and Neutropenia Guideline Panel recommended against the use of fungal biomarkers for the diagnosis of IFD in pediatric patients.
We conducted a retrospective chart review of pediatric oncology patients at UCM Comer Children’s Hospitals between July 2009 to December 2016 to determine the utility of BG and GM for diagnosis of IFD. Inclusion criteria: neutropenic fever (FN), high risk for IFD (fever > 5 days unresponsive to antibiotics or recurrent fever with persistent neutropenia), and ≥ 1 fungal biomarker sent. IFD was diagnosed using EORTC/MSG criteria with patients divided to 2 groups: “Proven or likely” and “less likely or unlikely”. Data pertaining to possible causes of false positive BG and GM was collected: presence of bacterial infection, receipt of immunoglobulin (IVIG), albumin or certain antibiotics (ie ampicillin/sulbactam or piperacillin/tazobactam)
Of 667 FN episodes (FNEs), 116 FNEs in 74patients were considered high-risk for IFD and had >1 biomarker sent. BG was sent on 76 FNEs and GM on 115 FNEs,. Underlying diagnoses included: Acute lymphoblastic leukemia (43 cases (37%)), acute myeloid leukemia (27 (24%)) lymphoma (12 (10%)) solid tumors (28 (24 %)) others (6 (5 %)). Overall, 59 (51%) cases underwent stem cell transplant. Of 15 deaths, 5 were related to fungal infection. Sensitivity, specificity, positive and negative predictive values for BG are 43%, 87%, 63% and 78%; respectively and for GM 15%, 95%, 50% and 79%; respectively. False positive BG was noted in 6 FNEs . False positive GM was noted in 4 FNEs (2 with non-Aspergillus molds, and 2 patient had bacteremia
Both BG and GM have low sensitivity and positive-predictive value supporting low utility in IFD diagnosis for pediatric patients. Our study shows a false positive BG may be as high as 250 pg/ml in the absence of clinical and radiological symptoms suggesting IFD. High specificity of the GM may be of value in diagnosing invasive Aspergillosis (IA). Novel fungal biomarkers are needed for early IFD detection to improve outcomes.
A. Bartlett, None