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

Mahajan, Prashant; Kuppermann, Nathan; Mejías, Asunción; Suárez, Nicolás M.; Chaussabel, Damien; Casper, T. Charles; Smith, B.; Alpern, Elizabeth R.; Anders, Jennifer; Atabaki, Shireen M.; Bennett, Jonathan E.; Blumberg, Stephen; Bonsu, Bema K.; Borgialli, Dominic; Brayer, Anne; Browne, Lorin R.; Cohen, Daniel M.; Crain, Ellen F.; Cruz, Andrea T.; Dayan, Peter; Gattu, Rajender; Greenberg, Richard A.; Hoyle, John D.; Jaffe, David M.; Levine, Deborah A.; Lillis, Kathleen; Linakis, James G.; Muenzer, Jared T.; Nigrovic, Lise E.; Powell, Elizabeth C.; Rogers, Alexander; Roosevelt, Genie; Ruddy, Richard M.; Saunders, Mary; Tunik, Michael G.; Tzimenatos, Leah; Vitale, Melissa; Dean, Jurrien; Ramilo, Octavio

doi:10.1001/jama.2016.9207

Cited by 184 publications

(162 citation statements)

References 34 publications

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“…29 However, we do know that the youngest infants with fever are infrequently pretreated with antibiotics. 16,18 Sixth, EV PCR testing decisions were at the discretion of the clinical team. Although we adjusted for patient age and study year, and clustering by center, we cannot fully control for clinical differences between tested and untested infants, raising the potential for unadjusted confounding.…”

Section: Discussionmentioning

confidence: 99%

“…Serious bacterial infection (SBI) was defined by the presence of any invasive bacterial infection or a urinary tract infection (UTI) 16 defined as a catheterized urine culture with ≥50,000 colony-forming units (CFUs)/mL of a single pathogenic bacteria or 10,000–50,000 CFUs/mL of a single pathogenic bacteria with an abnormal urinalysis (i.e., positive nitrite or leukocyte esterase test on urine dipstick or >5 WBCs/hpf on urine microscopy). 17,18 Cultures from which more than 1 bacterial species were isolated were considered contaminated unless 1 or more was a true pathogen. We defined a priori as contaminants normal skin or oral flora isolated from a bacterial culture of urine, blood, or CSF (Table I ; available at www.jpeds.com).…”

Section: Methodsmentioning

confidence: 99%

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Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

Aronson

Lyons

Cruz

et al. 2017

The Journal of Pediatrics

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Objective To determine the impact of a cerebrospinal fluid (CSF) enteroviral polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. Study design We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a CSF culture obtained at one of 18 participating centers (2005–2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an EV PCR test performed vs. not performed and among those tested, for infants with a positive vs negative test result. Results Of 19,953 hospitalized infants, 4,444 (22.3%) had an EV PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an EV PCR test performed compared with infants who did not (Incident rate ratio [IRR] 0.98 hours; 95% CI: 0.89–1.06 hours). However, EV PCR-positive infants had a 38% shorter LOS than EV PCR-negative infants (IRR 0.62 hours; 95% CI: 0.57–0.68). No infant with a positive EV PCR test had bacterial meningitis (0%; 95% CI: 0–0.4%). Conclusions While EV PCR testing was not associated with a reduction in LOS, infants with a positive EV PCR test had a one-third shorter LOS compared with infants with a negative EV PCR test. Focused EV PCR test use could increase the impact on LOS for infants undergoing CSF evaluation.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

Aronson

Lyons

Cruz

et al. 2017

The Journal of Pediatrics

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“…44 Mahajan et al demonstrated that RNA biosignatures could also distinguish bacterial from viral infections in infants ≤60 days of age with a sensitivity of 87% (95% CI: 73%–95%) and a specificity of 89% (95% CI: 81%–93%). 45 While these initial results are promising, the wide confidence limits related to the small sample size and lack of a rapid turn-around time may limit their widespread use. Future translational research should seek to validate the initial studies in a large enough sample to reliably evaluate the performance of this testing in a generalizable fashion.…”

Section: Are There New Diagnostic Tools That Can Be Incorporated Intomentioning

confidence: 99%

Management of the Febrile Young Infant

Woll

Neuman

Aronson³

2017

Pediatr Emer Care

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Infants ≤90 days of age with fever are frequently evaluated in the pediatric emergency department. Physical exam findings and individual laboratory investigations are not reliable to differentiate benign viral infections from serious bacterial infections in febrile infants. Clinical prediction models were developed over 25 years ago and have high sensitivity but relatively low specificity to identify bacterial infections in febrile infants. Newer laboratory investigations such as C-reactive protein (CRP) and procalcitonin (PCT) have favorable test characteristics compared to traditional laboratory studies such as a white blood cell count. These novel biomarkers have not gained widespread acceptance due to lack of robust prospectively collected data, varying thresholds to define positivity, and differing inclusion criteria across studies. However, CRP and PCT, when combined with other patient characteristics in the Step-by-Step approach have a high sensitivity for detection of serious bacterial infection. RNA biosignatures are a novel biomarker under investigation for detection of bacterial infection in febrile infants.

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“…19 However, clincians rarely administer antibiotics to the youngest infants prior to obtaining a CSF culture. 20,21 Additionally, we were unable to determine whether a child with a traumatic LP and bacteremia had bacterial meningitis. 17 However, as the rate of bacteremia for study infants was quite low, significant under-reporting of bacterial meningitis is unlikely.…”

Section: Limitationsmentioning

confidence: 99%

Interpretation of Cerebrospinal Fluid White Blood Cell Counts in Young Infants With a Traumatic Lumbar Puncture

Lyons

Cruz

Freedman

et al. 2017

Annals of Emergency Medicine

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Study Objective To determine the optimal correction factor for cerebrospinal fluid (CSF) white blood cell (WBC) counts in infants with traumatic lumbar punctures (LPs). Methods We performed a secondary analysis of a retrospective cohort of infants ≤ 60–days-old with a traumatic LP [CSF red blood cell (RBC) count ≥ 10,000 cells/mm3] at 20 participating centers. CSF pleocytosis was defined as a CSF WBC count ≥ 20 cells/mm3 for infants ≤ 28 days, ≥ 10 cells/mm3 for infants 29–60 day and bacterial meningitis as growth of pathogenic bacteria from CSF culture. Using linear regression, we derived a CSF WBC correction factor and compared the uncorrected to the corrected CSF WBC count for the detection of bacterial meningitis. Results Of the eligible 20,319 LPs, 2,880 (14%) were traumatic of whom 33 (1.1%) had bacterial meningitis. The derived CSF RBCs:WBCs ratio was 877:1 [95% confidence interval (CI) 805–961:1]. Compared with the uncorrected CSF WBC count, the corrected CSF WBC count had lower sensitivity for bacterial meningitis [88% uncorrected vs. 67% corrected; difference 21%, 95% CI 10–37%] but resulted in fewer infants with CSF pleocytosis [78% uncorrected vs. 33% corrected; difference 45%, 95% CI 43–47%]. CSF WBC count correction resulted in 7 additional infants with bacterial meningitis being misclassified as not having CSF pleocytosis; only one of these infants was > 28-days-old. Conclusion Correction of the CSF WBC count substantially reduced the number of infants with CSF pleocytosis while misclassifying only one infant with bacterial meningitis 29 to 60 days of age.

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

Cited by 184 publications

References 34 publications

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

Management of the Febrile Young Infant

Interpretation of Cerebrospinal Fluid White Blood Cell Counts in Young Infants With a Traumatic Lumbar Puncture

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