A novel, pathway-based gene set showed potential in differentiating bacterial from viral infections, and may help reduce unnecessary antibiotic use, according to research recently published in Scientific Reports.
In the United States, antibiotic-resistant bacteria cause at least 23,000 deaths and 2 million infections annually, according to a press release, which also stated that antibiotic use is the “single most important factor” in antibiotic resistance worldwide.
“Although sensitive molecular diagnostics such as polymerase chain reaction allow clinicians to rapidly and accurately diagnose a wide variety of respiratory viruses, their impact on management and antibiotic prescription has been modest primarily due to concern about bacterial co-infection,” Soumya Bhattacharya, MEd, MS, of the department of pediatrics, University of Rochester School of Medicine, and colleagues wrote.
“The study of bacterial lung infection has been hampered by insensitive tests for invasive disease and difficulty interpreting sputum cultures. Recently, serum biomarkers such as procalcitonin have shown some promise as a supplement to clinical judgment in assessing patients with [lower respiratory tract infections] but a need for more accurate tests remains.”
Researchers recruited 94 patients with lower respiratory tract infections, 53 of whom had viral infections or nonbacterial infections. Blood samples were taken from each participant.
Bhattacharya and colleagues found that qPCR and RNAseq validated significant differences in mean expression for 10 genes previously distinguished as discriminatory for bacterial lower respiratory tract infections. A dimension reduction strategy chose three pathways (IGF regulation, -linoleic acid metabolism, and lymphocyte) that contained 11 genes as optimal markers for discriminating bacterial infection (naïve area under the curve = 0.94; nested cross-validation–area under the curve = 0.86). Researchers used this information to build a classifier for bacterial lower respiratory tract infections with 83% (76% cross-validation) specificity and 90% (79% cross-validation) sensitivity.
“This report adds to mounting evidence that gene expression analysis of peripheral blood can be a useful test to discriminate bacterial and nonbacterial respiratory illness in hospitalized adults,” Bhattacharya and colleagues wrote. “Additional prospective studies are needed to define optimal predictive genes, with or without clinical variables and serum biomarkers, to assist clinicians in limiting unnecessary antibiotics for respiratory infections.”
“My goal is to develop a tool that physicians can use to rule out a bacterial infection with enough certainty that they are comfortable, and their patients are comfortable, foregoing an antibiotic,” Ann R. Falsey, MD, of infectious diseases division at the University of Rochester School of Medicine Strong Memorial Hospital, said in a press release.
Researchers have applied for a patent on their mechanism. – by Janel Miller
Falsey reports consulting for, and receiving research funding from, Janssen Pharmaceuticals. She has also received research funding from Gilead, Medimunne, Sanofi Pasteur and ADMA Biologics. Please see the study for a full list of the other researchers’ relevant financial disclosures.