Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger

被引：164

作者：

Mahajan, Prashant ^{[1
]}

Kuppermann, Nathan ^{[2
,3
]}

Mejias, Asuncion ^{[4
,5
,6
]}

Suarez, Nicolas ^{[4
,5
,6
]}

Chaussabel, Damien ^{[7
,8
]}

Casper, T. Charles ^{[9
]}

Smith, Bennett ^{[4
,5
,6
]}

Alpern, Elizabeth R. ^{[10
,11
]}

Anders, Jennifer ^{[12
]}

Atabaki, Shireen M. ^{[13
]}

Bennett, Jonathan E. ^{[14
]}

Blumberg, Stephen ^{[15
]}

Bonsu, Bema ^{[16
]}

Borgialli, Dominic ^{[17
,18
]}

Brayer, Anne ^{[19
,20
]}

Browne, Lorin ^{[21
,22
]}

Cohen, Daniel M. ^{[6
,23
]}

Crain, Ellen F. ^{[14
]}

Cruz, Andrea T. ^{[24
,25
]}

Dayan, Peter S. ^{[26
]}

Gattu, Rajender ^{[27
]}

Greenberg, Richard ^{[28
]}

Hoyle, John D., Jr. ^{[29
,30
,31
]}

Jaffe, David M. ^{[32
,33
]}

Levine, Deborah A. ^{[34
]}

Lillis, Kathleen ^{[35
]}

Linakis, James G. ^{[36
,37
]}

Muenzer, Jared ^{[34
,38
]}

Nigrovic, Lise E. ^{[39
]}

Powell, Elizabeth C. ^{[40
]}

Rogers, Alexander J. ^{[41
,42
]}

Roosevelt, Genie ^{[43
]}

Ruddy, Richard M. ^{[44
]}

Saunders, Mary ^{[21
,45
]}

Tunik, Michael G. ^{[34
]}

Tzimenatos, Leah ^{[2
]}

Vitale, Melissa ^{[46
]}

Dean, J. Michael ^{[9
]}

Ramilo, Octavio ^{[4
,5
,6
]}

机构：

[1] Wayne State Univ, Dept Pediat, Div Emergency Med, Childrens Hosp Michigan, Detroit, MI 48202 USA

[2] Univ Calif Davis, Sch Med, Dept Emergency Med, Sacramento, CA 95817 USA

[3] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA

[4] Nationwide Childrens Hosp, Div Pediat Infect Dis, Columbus, OH USA

[5] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Columbus, OH USA

[6] Ohio State Univ, Columbus, OH 43210 USA

[7] Virginia Mason & Sidra Med & Res Ctr, Benaroya Res Inst, Seattle, WA USA

[8] Virginia Mason & Sidra Med & Res Ctr, Benaroya Res Inst, Doha, Qatar

[9] Univ Utah, Dept Pediat, Salt Lake City, UT USA

[10] Childrens Hosp Philadelphia, Dept Pediat, Div Emergency Med, Philadelphia, PA 19104 USA

[11] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Chicago, IL 60611 USA

[12] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA

[13] George Washington Sch Med & Hlth Sci, Div Emergency Med, Dept Pediat, Childrens Natl Med Ctr, Washington, DC USA

[14] Alfred I DuPont Hosp Children, Div Pediat Emergency Med, Nemours Childrens Hlth Syst, Wilmington, DE USA

[15] Albert Einstein Coll Med, Dept Pediat, Jacobi Med Ctr, New York, NY USA

[16] Nationwide Childrens Hosp, Med Sect, Dept Pediat, Columbus, OH USA

[17] Hurley Med Ctr, Dept Emergency Med, Flint, MI USA

[18] Univ Michigan, Flint, MI 48503 USA

[19] Univ Rochester, Med Ctr, Dept Emergency Med, Rochester, NY 14642 USA

[20] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA

[21] Childrens Hosp Wisconsin, Dept Pediat, Med Coll Wisconsin, Milwaukee, WI 53201 USA

[22] Childrens Hosp Wisconsin, Dept Emergency Med, Med Coll Wisconsin, Milwaukee, WI 53201 USA

[23] Nationwide Childrens Hosp, Sect Emergency Med, Dept Pediat, Columbus, OH USA

[24] Texas Childrens Hosp, Baylor Coll Med, Sect Emergency Med, Houston, TX 77030 USA

[25] Texas Childrens Hosp, Baylor Coll Med, Sect Infect Dis, Houston, TX 77030 USA

[26] Columbia Univ Coll Phys & Surg, Dept Pediat, Div Emergency Med, New York, NY 10032 USA

[27] Univ Maryland, Dept Pediat, Med Ctr, Div Emergency Med, Baltimore, MD 21201 USA

[28] Univ Utah, Dept Pediat, Primary Childrens Med Ctr, Salt Lake City, UT USA

[29] Helen DeVos Childrens Hosp Spectrum Hlth, Dept Emergency Med, Grand Rapids, MI USA

[30] Western Michigan Univ Homer Stryker, Sch Med, MD, Dept Emergency Med, Kalamazoo, MI USA

[31] Western Michigan Univ Homer Stryker, Sch Med, MD, Dept Pediat, Kalamazoo, MI USA

[32] Washington Univ, Dept Pediat, St Louis Childrens Hosp, St Louis, MO 63130 USA

[33] Univ Calif San Francisco, Div Pediat Emergency Med, Sch Med, San Francisco, CA 94143 USA

[34] NYU, Dept Pediat, Langone Ctr, Bellevue Hosp, New York, NY 10016 USA

[35] SUNY Buffalo, Dept Pediat, Women & Childrens Hosp Buffalo, Buffalo, NY USA

[36] Hasbro Childrens Hosp, Dept Emergency Med & Pediat, Providence, RI USA

[37] Brown Univ, Providence, RI 02912 USA

[38] Phoenix Childrens Hosp, Dept Emergency Med, Phoenix, AZ USA

[39] Harvard Univ, Boston Childrens Hosp, Dept Pediat, Boston, MA 02115 USA

[40] Northwestern Univ, Dept Pediat, Div Emergency Med, Ann & Robert H Lurie Childrens Hosp Chicago,Feinb, Chicago, IL 60611 USA

[41] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA

[42] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA

[43] Univ Colorado Denver, Dept Pediat, Childrens Hosp Colorado, Aurora, CO USA

[44] Univ Cincinnati, Coll Med, Dept Pediat, Div Emergency Med,Cincinnati Childrens Hosp Med C, Cincinnati, OH USA

[45] Univ Colorado, Childrens Hosp Colorado, Sch Med, Aurora, CO USA

[46] Univ Pittsburgh, Sch Med, Dept Pediat, Div Pediat Emergency Med,Childrens Hosp Pittsburg, Pittsburgh, PA 15261 USA

来源：

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2016年 / 316卷 / 08期

基金：

美国国家卫生研究院;

关键词：

EMERGENCY-DEPARTMENT; BLOOD CULTURES; CHILDREN; EXPRESSION; BACTEREMIA; PATHOGENS; MICROBIOLOGY; TUBERCULOSIS; STRATEGIES; GENOMICS;

D O I：

10.1001/jama.2016.9207

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 degrees 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.

引用

页码：846 / 857

页数：12

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