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2016 ; 316
(8
): 846-57
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Association of RNA Biosignatures With Bacterial Infections in Febrile Infants
Aged 60 Days or Younger
#MMPMID27552618
Mahajan P
; Kuppermann N
; Mejias A
; Suarez N
; Chaussabel D
; Casper TC
; Smith B
; Alpern ER
; Anders J
; Atabaki SM
; Bennett JE
; Blumberg S
; Bonsu B
; Borgialli D
; Brayer A
; Browne L
; Cohen DM
; Crain EF
; Cruz AT
; Dayan PS
; Gattu R
; Greenberg R
; Hoyle JD Jr
; Jaffe DM
; Levine DA
; Lillis K
; Linakis JG
; Muenzer J
; Nigrovic LE
; Powell EC
; Rogers AJ
; Roosevelt G
; Ruddy RM
; Saunders M
; Tunik MG
; Tzimenatos L
; Vitale M
; Dean JM
; Ramilo O
JAMA
2016[Aug]; 316
(8
): 846-57
PMID27552618
show ga
IMPORTANCE: Young febrile infants are at substantial risk of serious bacterial
infections; however, the current culture-based diagnosis has limitations.
Analysis of host expression patterns ("RNA biosignatures") in response to
infections may provide an alternative diagnostic approach. OBJECTIVE: To assess
whether RNA biosignatures can distinguish febrile infants aged 60 days or younger
with and without serious bacterial infections. DESIGN, SETTING, AND PARTICIPANTS:
Prospective observational study involving a convenience sample of febrile infants
60 days or younger evaluated for fever (temperature >38° C) in 22 emergency
departments from December 2008 to December 2010 who underwent laboratory
evaluations including blood cultures. A random sample of infants with and without
bacterial infections was selected for RNA biosignature analysis. Afebrile healthy
infants served as controls. Blood samples were collected for cultures and RNA
biosignatures. Bioinformatics tools were applied to define RNA biosignatures to
classify febrile infants by infection type. EXPOSURE: RNA biosignatures compared
with cultures for discriminating febrile infants with and without bacterial
infections and infants with bacteremia from those without bacterial infections.
MAIN OUTCOMES AND MEASURES: Bacterial infection confirmed by culture. Performance
of RNA biosignatures was compared with routine laboratory screening tests and
Yale Observation Scale (YOS) scores. RESULTS: Of 1883 febrile infants (median
age, 37 days; 55.7% boys), RNA biosignatures were measured in 279 randomly
selected infants (89 with bacterial infections-including 32 with bacteremia and
15 with urinary tract infections-and 190 without bacterial infections), and 19
afebrile healthy infants. Sixty-six classifier genes were identified that
distinguished infants with and without bacterial infections in the test set with
87% (95% CI, 73%-95%) sensitivity and 89% (95% CI, 81%-93%) specificity. Ten
classifier genes distinguished infants with bacteremia from those without
bacterial infections in the test set with 94% (95% CI, 70%-100%) sensitivity and
95% (95% CI, 88%-98%) specificity. The incremental C statistic for the RNA
biosignatures over the YOS score was 0.37 (95% CI, 0.30-0.43). CONCLUSIONS AND
RELEVANCE: In this preliminary study, RNA biosignatures were defined to
distinguish febrile infants aged 60 days or younger with vs without bacterial
infections. Further research with larger populations is needed to refine and
validate the estimates of test accuracy and to assess the clinical utility of RNA
biosignatures in practice.