Superiority of Transcriptional Profiling Over Procalcitonin for Distinguishing Bacterial From Viral Lower Respiratory Tract Infections in Hospitalized Adults

Abstract

Transcriptional profiling is a helpful tool for diagnosis of LRTI.

Robust classification of bacterial and viral infections via integrated host gene expression diagnostics

“…We next tested the seven-gene set in the six remaining independent clinical cohorts (13, 14, 27–29) that directly compared bacterial and viral infections (138 bacterial and 203 viral infections, totaling 341 samples) and found a summary ROC AUC of 0.91 (95% CI, 0.82 to 0.96) (Fig. 1, Table 1B, and fig.…”

“…Most of these classifiers were not tested in multiple independent cohorts, had too many genes to allow rapid profiling necessary for useful diagnosis, or both. For instance, Suarez et al created a 10-gene k -nearest-neighbor classifier but did not test it outside their published data set (GSE60244) (13). Tsalik et al created a 122-probe (120-gene) classifier on the basis of multiple regression models, but in testing it in external GEO cohorts, they retrained their regression coefficients in each new data set (14).…”

Host-Based Peripheral Blood Gene Expression Analysis for Diagnosis of Infectious Diseases

“…Gene expression profiles from pediatric patients infected with influenza A virus were compared to those from patients with bacterial infections due to Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli, and a 35-gene classifier was developed and successfully discriminated between patients with influenza A virus and those with bacterial infections with 91% accuracy (8). These findings were further confirmed in an adult cohort of hospitalized patients, where gene expression-based classifiers were shown to be superior to a single-analyte biomarker, procalcitonin (sensitivity of 95% versus 38% and specificity of 92% versus 91%, respectively) (19). More recent work led to the development of an RT-PCR-based classifier that accurately separates acute upper respiratory illness into bacterial infection, viral infection, bacterium-virus coinfection, or noninfectious causes (20).…”

New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance

“…In 2007, Ramilo et al first described host gene expression signatures discriminating bacterial and viral infection. 26 Since that time, additional studies have focused on adult and pediatric cohorts 27,28 ; discriminated different types of viral infection 29 ; distinguished infection from colonization 30 ; identified pre-symptomatic disease states 31 ; added non-infectious illness as more appropriate controls 28 ; and showed superiority to existing biomarkers (i.e., PCT) 28,32 . As important as each of these (and many more) studies have been, they all occurred at the pre-clinical stage of development.…”