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Andi Marmor, MD, MSEdUCSF Associate Professor, PediatricsDecember, 2014

� Nearly 20% of febrile infants have “fever without a source” (FWS)� A few, although well-appearing, have an occult

bacterial infection:� UTI: Most common, simple to dx/treat� SBI (bacteremia/meningitis): Harder to diagnosis,

worse to miss, decreasing in prevalence

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

� Rhizobium (“Rizzo”) is a 15 day old boy whose mother reports that he felt warm today� The whole family has a cold, and Rizzo has

coughed a few times� VS: T 37.9 (R), P 145, R 35,

BP 70/40� Slightly fussy, but normal

exam, feeding well

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A. UnreliableB. As accurate as a rectal temperatureC. More sensitive than specificD. Usually due to over-bundling

U n re l i a

b l e

A s a c c

u r at e a

s a r e c t

a l t. . .

M or e s

e n si t i v

e t ha n

s p ec i f i c

U s ua l l y

d ue t o

o ve r - b

u n d. . .

30%

15%

49%

6%

� Parents better at ruling outthan ruling in

� UTI/SBI more likely with documented fever than with reported1

� Vaccines?� One time fever� May occur 1-3 day later

1Yarden-Bilavsky, 2010

Icanhazcheeseburger.com

� Neonates with FWS are at high risk of bacterial infection� Occult infection: 15-20%� ~90% of these are UTI’s� Bacteremia with UTI is

common (10-15%)� Has the epidemiology of UTI/SBI in neonates

changed?Greenhow et al, Epi of SBI in young infants. Pediatr Infect Dis J; 2014

2-3%

Better GBS screening?13-18%(92% of total)

<1%

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A. S. pneumo, H. influenza, N. meningitidisB. E. Coli, S. pneumo, Group B StrepC. E. Coli, Group B Strep, ListeriaD. E. Coli, Group B Strep, S. aureusE. Group B Strep, S. pneumo,

H. influenza

S . pn e u

m o, H .

i n fl u e

n z a, . . .

E . Co l i ,

S . pn e u

m o, G r

o u p. .

E . Co l i ,

G r ou p

B S tr e p

, L i s. . .

E . Co l i ,

G r ou p

B S tr e p

, S . .. .

G r ou p B

S t re p ,

S . pn e u

m o,

5%

20%

13%

35%

27%

TABLE 3 . Bacterial Pathogens Detected in 129 Blood, 823 Urine and 16 CSF Cultures

� Notice anything missing?Greenhow et al, Pediatr Infect Dis J; 2014

A. S. pneumo, H. influenza, N. meningitidisB. E. Coli, S. pneumo, Group B StrepC. E. Coli, Group B Strep, ListeriaD. E. Coli, Group B Strep, S. aureusE. Group B Strep, S. pneumo, H. influenza

� E. Coli the most common cause of all types of bacterial infections� Staph and enterococcus are emerging

pathogens� Listeria is no longer a major player� Amp/Cefotaxime remains a good choice� Cefotaxime for broad GP and GN coverage� Amp for enterococcus (not listeria!)

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� Clinical appearance, WBC: poor predictors

Greenhow et al, Pediatr Infect Dis J; 2014

Schwartz, 2009

• Risk of UTI/SBI decreases with age• Reliability of ill appearance increases with age

� UTI is the most common bacterial infection � Ill appearance/low-risk criteria are not reliable

in neonates� E. coli is the most common cause of ALL

UTI/SBI in neonates� GBS the major cause of non-UTI SBI� Enterococcus, staph are emerging pathogens

� In general: collect urine, blood and CSF for culture, and start broad-spectrum antibiotics� Ampicillin/cefotaxime

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� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

� In general: collect urine, blood and CSF for culture, and start broad-spectrum antibiotics� Ampicillin/cefotaxime� Risk stratification/observation can be

considered in select circumstances� Multiple reassuring factors (eg: no documented

fever, + viral infection AND LRC met…)

� You decide to get a CBC and blood culture, a cath UA/culture and a rapid flu/RSV test� Results:� WBC 15, with 33% neutrophils� CRP is 1.2 mg/dL (normal)� Rapid viral test positive for influenza� Cath U/A negative

1. Start antibiotics, admit2. LP, antibiotics, admit3. No LP, no antibiotics, admit for observation

overnight4. Observe clinic/ED for 12 hours for fever

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1. Start antibiotics, admit2. LP, antibiotics, admit3. No LP, no antibiotics, admit for observation

overnight4. Observe clinic/ED for 12 hours for fever

All except #1 are OK

� Rochalimea is a 7 week old girl with cough and fever for 2 days at home� VS: T 38.9, P 150’s, R 30’s, O2 sat 100%� On exam, she is well-appearing, lungs are

clear, she has slight crusting at the nares, no other findings

� UTI � Common in girls and

uncircumcised boys (10-15%)

� SBI (1-2%)� S. pneumo becomes the predominant pathogen� Significant decrease since S. pneumo vaccination� Still a few cases of E. Coli, GBS, others

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

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� Focal bacterial infection (otitis media, cellulitis)� Consider further W/U in neonates�Named viral infection (bronchiolitis, croup)

OR + viral test � Infants < 3 months: still consider UTI� Infants > 3 months: SBI/UTI unlikely�Clear URI symptoms in infants > 3 mo of age

� Focal bacterial infection (otitis media, cellulitis)� Consider further W/U in neonates�Named viral infection (bronchiolitis, croup)

OR + viral test � Infants < 3 months: still consider UTI� Infants > 3 months: SBI/UTI unlikely�Clear URI symptoms in infants > 3 mo of age

� While her nonspecific URI symptoms don’t constitute a clear source, you decide the most helpful initial test is a urinalysis. � Cath UA: 2+ for LE, + nitrites� Due to her age, you decide to get a blood

culture and admit her for pyelo� Do you need to do an LP before starting abx?

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

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� Bacteremia is frequent in infants < 3 mo with febrile UTI (10-15%)� However, meningitis with UTI is extremely

rare in well-appearing infants� A few cases of meningitis with UTI in well-

appearing neonates been reported� LP is not recommended routinely in infants >

1 mo if treating for pyeloPaquette, 2011

� Anaplasma, a 2 mo old boy, presents to the ED with 2 days of tactile fever, no other symptoms� Unimmunized� Circumcised� T= 38.9, P 150, R 40’s, BP 90/65� Well-appearing, well-hydrated� UA negative� RVT negative for influenza/RSV

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

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� UTI: Urinalysis – 1 hr� Meningitis: CSF cell

counts – 1 hr� Pneumonia: Clinical

diagnosis/CXR – 1 hr� Bacteremia: Blood

culture – 2 days!!!!� The only REALLY occult

SBI !Andreola, 2007

Perfect test

� Most useful in infants 1-3 mo of age (low-mod risk) to R/O bacteremia� Best negative predictive value � Does NOT reliably R/O UTI ( but we have

another test for that)� May have selective utility in otherwise low-

risk neonates � Only when it will change management…

� You send a CBC and CRP:� WBC 16.7 (5-15), CRP 5.0 mg/dL (< 2)� Next step?� Tap, treat, admit

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� Screen for UTI in all infants <3 mo with FWS� If UA +, get blood culture and treat for UTI� If UA negative consider RVT � If UA and RVT neg, labs can help stratify risk of

SBI� LOW risk for SBI if ▪ WBC count 5-15K▪ PCT < 0.2 ng/ml▪ CRP <2.0 mg/dL

� Screen for UTI selectivelybased on age/gender� Uncircumcised boys < 6 mo� Girls < 24 mo, if fever > 48 hrs� Otherwise, infants > 3 mo are at low risk for

occult SBI � Even unvaccinated infants are protected� Empiric labs/antibiotics NOT recommended

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

A. Reduce discomfort/metabolic stressB. Reduce risk of seizuresC. Document fever’s response to

antipyreticsD. Decrease risk of brain damageE. Help the immune system fight

infection

R e du c e

d i sc o m

f o r t/ m e

t a . ..

R e du c e

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s

D o cu m

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. . .

H e lp t h

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m .. .

63%

28%

0%3%6%

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� Benefits of fever?� Suggested in animal

studies, ICU pts� Dangers of fever?� Discomfort, increased

metabolism, fluid loss� Fever phobia� NOT febrile seizures

� < 50% of parents can define fever (> 38.5 C)� 15-40 % think fever can cause brain damage,

seizure or death� Antipyretic dosing errors common� Social/ethnic differences� Latino parents: most concerned, prefer tactile � AA parents: most likely to overdose antipyretics� Lower level of education = higher fever concern

Cohee (2009), Poirier (2010)

� Primary benefit is comfort� In clinic: may make child easier to assess!� Ibuprofen safe, well-tolerated and effective� Use acetaminophen if ibuprofen contraindicated� Alternating NOT recommended� Sponging/cooling not effective and may cause

hypothermia

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

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� Do all neonates need the full ROS workup?� While SBI less common, ill appearance/low-risk

criteria still not reliable in neonates� Observation without antibiotics only in very select

circumstances (-UA, +RVT, well, etc)� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� In infants > 1 mo, named bacterial, viral illness OR

+ RVT can be considered a source� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� Not in a well-appearing infant > 1 month� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?

� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs (CBC, CRP, PCT)� Infants 1-3 mo, without viral source or UTI� CRP/PCT more sensitive/specific than CBC� When and how should fever be treated?

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� Do all neonates need the full ROS workup?� What counts as a fever “source”?� If urine is +, do I need to do an LP?� What is the role for labs – CBC, CRP, PCT?� When and how should fever be treated?� When child is uncomfortable/distressed� Ibuprofen preferred� Educate parents on treatment/supportive care!

Rhizobium

Rochalimaea

Anaplasma