1218 - Comparing the Diagnostic Accuracy of Clinician Judgement to a Novel Host Response Diagnostic for Acute Respiratory Illness

Background: Discriminating bacterial and viral infections remains clinically challenging. The resulting antibacterial misuse contributes to antimicrobial resistance. Host gene expression-based tests are a promising strategy to discriminate of bacterial and viral infections, but their potential clinical utility has not yet been evaluated.

Methods: A host gene expression biosignature was measured using either qRT-PCR or microarray in 683 ED subjects with suspected infection. Based on chart reviews, we recorded clinical diagnosis as defined both by the provider assessment and by the provider treatment plan. The biosignature, diagnosis, treatment plan, and procalcitonin were compared to clinical adjudication as the reference standard. With this as a baseline, we then calculated average weighted accuracy (AWA) and change in overall net benefit (∆NB), weighting bacterial false negatives four times more seriously than false positives.

Results: Gene expression correctly classified the three possible disease etiologies (bacterial, viral, or non-infectious) 76.1% of the time, outperforming provider diagnosis, provider treatment, and procalcitonin (Table 1). Overall accuracy was higher in subjects with bacterial infections (n=278, 83.8% accurate) compared to those with viral (n=234, 76.5%) and non-infectious (n=171, 63.2%) etiologies. Due to a strong sensitivity bias to treat bacterial infections at the expense of diagnostic accuracy and specificity, the provider diagnosis was overall more accurate than the corresponding treatment plan (71.4% accuracy vs. 68.1%), resulting in inappropriate antibiotic use in 41.0% of cases where antibiotics were prescribed. The gene expression test had significantly higher AWA for the diagnosis of bacterial infection than both procalcitonin and provider treatment (82.4% vs. 70.3% and 74.4%, respectively; p < 0.0001). Consequently, the host gene expression test had greater net benefit than provider treatment (∆NB_bact = 9.9%), provider diagnosis (∆NB_bact = 4.4%), and procalcitonin (∆NB_bact = 27.1%).Table 1: Summary of provider, procalcitonin, and host gene expression test performance in a cohort of 683 subjects.


Conclusion: Host gene expression-based tests to distinguish bacterial and viral infection can facilitate more appropriate treatment, leading to improved patient outcomes and mitigating the antibiotic resistance crisis.