1. Management of the Febrile Young Infant in 2019
Paul L. Aronson, MD
Associate Professor of Pediatrics and of Emergency Medicine
Section of Pediatric Emergency Medicine
Yale School of Medicine

2. Disclosures
I have no conflicts of interest or relevant financial relationships to disclose
My research supported by:
NCATS/NIH CTSA grant number KL2 TR001862
AHRQ grant number 1K08HS A1

3. Objectives
Compare the modified Philadelphia criteria, Step-by-Step approach, and PECARN prediction rule
Interpret the evidence for routine vs. selective lumbar puncture in febrile infants ≤60 days of age

4. Definitions Fever Young infant Serious Bacterial Infection (SBI)
Rectal temp ≥38.0 C (100.4 F)
Young infant
<90 days old (many use ≤60 days)
Neonate: ≤28 days old
Serious Bacterial Infection (SBI)
UTI
Bacteremia and/or bacterial meningitis (i.e., invasive bacterial infection [IBI])
Full “workup”
Urine, Blood, CSF

5. Fever in the Young Infant
~ 160,000 febrile infants ≤60 days of age evaluated each year in an emergency department (ED)
Wier LM et al. HCUP 2006; Baskin MN. Pediatr Ann 1993; Aronson PL et al. Pediatrics 2014
~ 10% will have a bacterial infection
Up to 20% in neonates ≤28 days old
Huppler AR et al. Pediatrics 2010; Schwartz S et al. Arch Dis Child 2009
Most bacterial infections are Urinary Tract Infection (UTI)
Vast majority identified by urinalysis
(positive leukocyte esterase or nitrites, or >5 WBC/hpf)
Risk of adverse outcome low
Huppler AM et al. Pediatrics 2010; Tzimenatos L et al. Pediatrics 2018; Schnadower D et al. Pediatrics 2010

6. Invasive Bacterial Infection
Bacteremia and/or Bacterial Meningitis
E. Coli, GBS, S. aureus, Enterococcus, other gram+/gram-
Powell EC et al. Ann Emerg Med 2018; Woll C et al. J Pediatr 2018
Prevalence ~ 2% among febrile infants
Greenhow TL et al. Pediatrics 2012; Greenhow TL et al. Pediatr Infect Dis J 2014; Powell EC et al. Ann Emerg Med 2018
Risk of mortality and neurologic morbidity if untreated
de Louvois J et al. Eur J Pediatr 2005; Tsai MH et al. Pediatr Infect Dis J 2014
Clinical appearance or individual laboratory tests not sensitive indicators for IBI
Baker MD et al. Pediatrics 1990; Hui C et al. Evid Rep Technol Assess (Full Rep) 2012; Nigrovic LE et al. Pediatrics 2017

7. Newer Algorithms to Risk Stratify Febrile Infants
Classify febrile infants as “low-risk” or “not low-risk”
Do not include routine cerebrospinal fluid testing for risk stratification

8. Modified Philadelphia criteria
Low Risk Factors
Age Cutoff
29-56 days
Past Medical History
Previously healthy
Clinical Appearance
Well-appearing
Physical Examination
No skin or soft tissue infection
Laboratory
Normal Urinalysis
WBC ≥5,000 and ≤15,000
I:T Ratio <0.2
Low-risk
All of the above present

9. Step-by-Step Approach
Low Risk Factors
Age Cutoff
>21 days
Clinical Appearance
Well-appearing
Laboratory
No leukocyturia
PCT <0.5 ng/mL
CRP ≤20mg/L
ANC ≤10,000/mm3
Low-risk
All of the above present

10. PECARN Prediction Rule
Low Risk Factors
Age Cutoff
None
Past Medical History
No chronic condition or prematurity
Clinical Appearance
Not Critically ill
Physical Examination
No skin or soft tissue infection
Laboratory
Normal Urinalysis
ANC ≤4,090/mm3
PCT ≤1.71 ng/mL
Low-risk
All of the above present

11. Performance Characteristics of Risk Stratification Algorithms for IBI
Overall
Sensitivity
(95% CI)
Specificity
Modified Philadelphia Criteria
29-56 days; Non-low risk if ≤28 days
91.9% ( )
34.5% ( )
Step-by-Step Approach
≤90 days; Non-low risk if ≤21 days (? ≤28 days)
92.0% ( )
46.9% ( )
PECARN Prediction Rule
≤60 days
96.7% ( )
61.5% ( )
Infants who had an EV PCR test performed had a similar age distribution to infants without an EV PCR test.
Gomez et al. Pediatrics 2016; Aronson et al. Pediatrics 2018; Kuppermann N et al. JAMA Pediatr 2019

12. Performance Characteristics of Risk Stratification Algorithms for IBI
Overall
Sensitivity
(95% CI)
Specificity
Modified Philadelphia Criteria
29-56 days; Non-low risk if ≤28 days
91.9% ( )
34.5% ( )
Step-by-Step Approach
≤90 days; Non-low risk if ≤21 days (? ≤28 days)
92.0% ( )
46.9% ( )
PECARN Prediction Rule
≤60 days
96.7% ( )
61.5% ( )
Infants who had an EV PCR test performed had a similar age distribution to infants without an EV PCR test.
Gomez et al. Pediatrics 2016; Aronson et al. Pediatrics 2018; Kuppermann N et al. JAMA Pediatr 2019

13. Performance Characteristics of Risk Stratification Algorithms for IBI
Overall
Sensitivity
(95% CI)
Specificity
Modified Philadelphia Criteria
29-56 days; Non-low risk if ≤28 days
91.9% ( )
34.5% ( )
Step-by-Step Approach
≤90 days; Non-low risk if ≤21 days (? ≤28 days)
92.0% ( )
46.9% ( )
PECARN Prediction Rule
≤60 days
96.7% ( )
61.5% ( )
Infants who had an EV PCR test performed had a similar age distribution to infants without an EV PCR test.
Gomez et al. Pediatrics 2016; Aronson et al. Pediatrics 2018; Kuppermann N et al. JAMA Pediatr 2019

14. Performance Characteristics of Risk Stratification Algorithms for IBI
Overall
Sensitivity
(95% CI)
Specificity
Modified Philadelphia Criteria
29-56 days; Non-low risk if ≤28 days
91.9% ( )
34.5% ( )
Step-by-Step Approach
≤90 days; Non-low risk if ≤21 days (? ≤28 days)
92.0% ( )
46.9% ( )
PECARN Prediction Rule
≤60 days
96.7% ( )
61.5% ( )
Infants who had an EV PCR test performed had a similar age distribution to infants without an EV PCR test.
Gomez et al. Pediatrics 2016; Aronson et al. Pediatrics 2018; Kuppermann N et al. JAMA Pediatr 2019

18. Bottom Line No algorithm is 100% sensitive for IBI
Be cautious in neonates ≤28 days of age
If low-risk, need to ensure close PCP f/u within 24 hours and provide clear and detailed discharge instructions
Yale: Most now use the Step-by-Step approach
Procalcitonin results available in as little as 1 hour
But….what about the lumbar puncture?

19. Prevalence of Meningitis in Low-risk Infants
? 0%
But….this is an imprecise estimate
Modified Philadelphia: 17 infants with meningitis (but 26 others who were ill-appearing)
Step-by-Step: 10 infants with meningitis
PECARN: 10 infants with meningitis
Be very cautious in neonates ≤28 days

20. Decision on Lumbar Puncture is a Scale….
Low prevalence of bacterial meningitis
Downsides of lumbar puncture
Bacterial meningitis is bad
Lumbar puncture is “safe”

21. Two viable management options for low-risk infants in the ED
1) Lumbar puncture +/- hospitalization
2) No lumbar puncture and discharge home
(No lumbar puncture and hospitalize off antibiotics)
Risk/benefit ratio uncertain
Should incorporate parents’ values and preferences
Shared-decision making process recommended by Institute of Medicine, American Academy of Pediatrics

22. The Big Caveat for General EM Providers
Err on the side of caution
If you are not comfortable with “well-appearance” for a young infant, do the lumbar puncture (or transfer to pediatric ED)
If you cannot guarantee outpatient follow-up, have a low threshold to do the lumbar puncture and admit

23. Questions and Discussion