Background and Objective: Reliably distinguishing between bacterial and viral infections in febrile children is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-response proteins (TRAIL, IP-10 and CRP) was recently developed to assist in differentiation between bacterial and viral disease. We performed double-blind, multi-center assay evaluation.
Methods: Infectious and non-infectious children presenting to 5 pediatric emergency departments and inpatients aged ≥3 months to ≤18 years were retrospectively enrolled. Inclusion criteria for the infectious cohort were: suspicion of acute infection, fever ≥38°C, antibiotic treatment ≤48 hours and symptom duration ≤7 days. Reference standard diagnosis was based on predetermined criteria plus adjudication by an expert panel blinded to assay results. Assay performers were blinded to reference standard. Assay cutoffs were defined before un-blinding.
Results: Of 597 potentially eligible patients, 56 were non-infectious, 101 did not fulfill infectious inclusion criteria and 79 had insufficient serum. The resulting infectious cohort comprised 361 patients: 239 viral, 68 bacterial, and 54 with indeterminate etiology. The assay distinguished between bacterial and viral infected patients with 93.8% sensitivity (95% CI: 87.8%-99.8%) and 89.8% specificity (85.6%-94.0%); 11.7% had an equivocal assay outcome. Assay outperformed other clinical parameters. CRP (cutoff 40 mg/L): sensitivity 88.2% (80.4%-96.1%), specificity 73.2% (67.6%-78.9%). PCT (cutoff 0.5 ng/ml): sensitivity 63.1% (51.0%-75.1%), specificity 82.3% (77.1%-87.5%).
Conclusions: Assay performance was validated in febrile children in a double-blinded study. Assay was more accurate than CRP, PCT and routine clinical parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.
