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RNA biosignatures identify bacterial infections in febrile newborns
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Host RNA biosignatures identified in a small sample of blood distinguished between bacterial and nonbacterial infections in febrile newborns, according to recently published study findings.
“Febrile infants aged 60 days or younger are at substantial risk of serious bacterial infections, estimated at 7% to 9% in this population,” Prashant Mahajan, MD, MPH, MBA, division chief and research director of pediatric emergency medicine at Children’s Hospital of Michigan, and colleagues from the Pediatric Emergency Care Applied Research Network (PECARN) wrote. “Current guidelines recommend obtaining blood, urine and cerebrospinal fluid cultures, with consideration of antibiotic treatment and hospitalization until culture results are negative.”
To evaluate whether a bacterial infection in infants can be discerned from another infection, Mahajan and colleagues enrolled infants aged 2 months and younger who presented with fever and had blood drawn in 22 ERs between December 2008 and December 2010. RNA biosignatures were analyzed from 279 randomly selected infants with bacterial infections (n = 89) and without bacterial infections (n = 190). Infants without fever (n = 19) served as healthy controls.
The PECARN team identified a biosignature in 66 classifier genes from the small blood cultures of febrile infants that distinguished bacterial infections with 87% sensitivity (95% CI, 73-95) and 89% (95% CI, 88-98) specificity. These included urinary tract infections, bacterial meningitis and bacteremia. Ten genes identified a positive sample of bacteremia in infants with 94% accuracy and 95% specificity, and the incremental C statistic over the Yale Observation Scale (YOS) was 0.37 (95% CI, 0.3-0.43) for the RNA biosignatures.
“The clinical utility of the RNA biosignatures in the evaluation of febrile infants will ultimately be determined by their ability to exclude the diagnosis of serious bacterial infections rapidly and reliably,” the researchers wrote. “The biosignatures contributed substantially more than the YOS in identifying those with bacterial infections.
“Most importantly, the posttest negative probabilities for bacteremia and bacterial meningitis were very low, suggesting future clinical application of RNA biosignatures for excluding serious bacterial infections in febrile infants aged 60 days or younger.” – by Kate Sherrer
Disclosure: This study was funded in part by NICHD/NIH. Mahajan reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
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