Transcript A 21st Century Approach to Fever in Infants and Young Children

A 21st Century Approach
to Fever in Infants and
Young Children
James M Callahan, MD
Division of Emergency Medicine
Department of Pediatrics
The Children’s Hospital of Philadelphia
University of Pennsylvania
School of Medicine
A pediatric healthcare network
Disclosures
• James M Callahan, MD
I have no relevant financial relationships to
disclose or conflicts of interest to resolve.
This presentation will not involve discussion of
unapproved or off-label, experimental or
investigational use medications or devices.
2
Objectives
• After this session, participants will be able to:
– Discuss the bacteriology of serious infections in
children less than three months of age.
– Discuss the bacteriology of bacteremia in children
3 – 36 months of age.
– Discuss an approach to management of febrile
infants less than 3 months of age.
– Discuss an approach to children 3 – 36 months of
age with fever without a source in an era of
widespread pneumococcal vaccination.
– Discuss the importance of urinary tract infections
as a source of fever in young children.
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Fever in Infants and Young Children
• Introduction
• Fever in the First Three Months of Life
• Fever in Children 3 – 36 Months of Age
– Occult Bacteremia
– Urinary Tract Infections
– Febrile Seizures
• Summary
4
Fever
Scope of the Problem
• Common presenting complaint in children
• 20% of pediatric visits to ED’s are for a
chief complaint of fever; common “sick
visit” complaint in offices
• The majority of these children are less
than three years old
• Fever accompanies both minor and life –
threatening infections
5
Definition of Fever
• A rectal temperature of > 38°C in an
appropriately dressed child at rest for
30 minutes.
• Life – threatening, infectious disease
may be present in young infants without
fever.
• Hypothermia in young infants is an
ominous sign.
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Fever Phobia
• The public, especially parents fear fever.
• Rarely does fever itself cause problems.
• Extreme fevers (T > 41.1°C or 106°F) are
more likely to result from environmental
heat excess.
• Fever has an evolutionary role.
• Fever’s significance and possible
beneficial role need to be explained.
• It alerts us to an underlying illness to
diagnose and treat, if necessary.
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Fever and antipyretic use
• AAP Technical Report – 2011
–
–
–
–
Appropriate counseling for parents
Fever is not dangerous in healthy children
Fever may be a benefit
Fever is not the same as hyperthermia
– Sullivan JE, et al. Pediatrics 2011
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Fever and antipyretic use
• AAP Technical Report – 2011
– Goal of antipyretics – comfort
• Not normalizing temperature
• Acetaminophen and ibuprofen both safe and
effective in appropriate doses
• Combination therapy not shown to be
beneficial – may increase dosing errors
– Health care provider role:
• Minimize “fever phobia”
• Emphasize monitoring for signs and
symptoms of serious disease
– Sullivan JE, et al. Pediatrics 2011
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Fever:
Management and Approach
• The management of fever depends on:
–
–
–
–
–
–
10
Severity of illness
Age of the patient
Focus of infection, if any
Height of the fever
Immune status of the patient
Practice setting
Fever in the First Three Months:
Usual Pathogens
• E. coli
• Other gram negative
enterics
• Group B
streptococcus
• Lysteria
monocytogenes
• H. influenzae type B
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Fever in the First Three Months:
Epidemiology
• Infants have:
– Higher rates of bacteremia and SBI.
– Are less immunocompetent.
– Unreliable physical examinations.
• 3 – 15% of febrile infants < 3 mo will have a SBI.
• Academic standard of care has been a sepsis
work – up.
• A septic appearing infant should prompt a broad
differential diagnosis.
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Fever in the First Three Months:
History of Fever
• An infant presents with a history of tactile
or rectal fever at home and without
antipyretics is now afebrile:
– 0/26 of infants with a history of tactile
fever were febrile during hospitalization.
– 8/40 infants with history of rectal fever
were febrile.
– 19/19 infants with SBI had an abnormal
exam or abnormal lab values.
• Bonadio, et al. Pediatr Infect Dis J 1990.
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Management:
Infants 0 – 28 Days Old
• All children < 29 d old
should have a full sepsis
workup with LP, be
admitted to the hospital
and receive parenteral
antibiotics pending
cultures.
• Labs and exam not good
predictors (negative
predictive value of only
88% at best)
• The LP is necessary.
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Management:
Infants 29 – 89 Days Old
• Baskin, O’Rourke, Fleisher:
– J Pediatr 1992
– Age 29 – 89 d; T > 38°c
– Normal PE
– Normal labs:
•
•
•
•
CSF < 10 wbc
UA – negative L.E.
Normal CXR
WBC < 20k
– All given 50 mg/kg CTX IM and discharged.
– Repeat exam and CTX in 24 h if culture
negative.
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Management:
Infants 29 – 89 Days Old
• Baskin, O’Rourke, Fleisher:
– J Pediatr 1992
• Results:
– 503 patients
• 27 (5%) with SBI
–
–
–
–
8 bacteremia
1 UTI/bacteremia
8 UTI
10 bacterial gastroenteritis
– All subsequently treated and did well
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Management:
Infants 29 – 89 Days Old
• Baker, Bell, Avner:
– New Engl J Med 1993
– Age 29 – 56 days; T > 38.2°C.
– Normal PE (I.O.S.).
– Normal labs:
•
•
•
•
WBC 5 – 15K; BNR < 0.2
UA < 10 wbc/hpf; < few bacteria
CSF < 7 wbc; normal GS, glc, pro
Normal CXR
– Randomized management.
– Re – examined at 24 and 48 hours.
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Management:
Infants 29 – 89 Days Old
• Baker, Bell, Avner:
– New Engl J Med 1993
• Results:
– 747 infants
• 1/65 with SBI had a negative screen
• NPV 99% (95% C.I. 98 – 100)
• $3300 – 5500 vs. $785
• Follow – up studies:
– 420 infants
– 0/43 with negative screen with SBI
– Baker, et al. Pediatrics 1999
• Reliable in a different population
– Garra, et al. Acad Emerg Med 2005
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Management:
Infants 29 – 89 Days Old
• Baraff, et al.:
– Ann Emerg Med 1993
• Meta – analysis and consensus guidelines
• Low risk criteria:
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–
–
–
–
–
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Previously healthy
No focal infection
WBC 5 – 15K
Bands < 1500
Normal UA
In children with diarrhea: stool wbc < 5/hpf
Management:
Infants 29 – 89 Days Old
• Baraff, et al.:
– Ann Emerg Med 1993
• Option 1 – Low Risk Infants
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–
–
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Blood culture
Urine culture
LP
CTX 50 mg/kg IM and recheck in 24 h
• Option 2 – Low Risk Infants
– Urine Culture
– Careful observation
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Rochester: More than a city in
Upstate New York
• Criteria
–
–
–
–
No focal infection
5,000 < WBC < 15,000
Absolute bands < 1,500
U/A < 10 wbc/hpf; stool < 5 wbc/hpf if diarrhea
• Results
– NPV ~ 98% - original study and follow-up by same group
• Criticism – Pro and Con
– No LP
– 13 of 27 patients with SBI in another study missed
– Recent report – new population NPV 97.3%
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Management:
Young Infants with RSV
• Titus, Wright. Pediatrics 2003
– Retrospective, cohort
– 174 infants < 8 w with RSV: 2 with SBI (UTI)
– 174 infants < 8 w without RSV: 22 with SBI
• Conclusions
– Risk of SBI in febrile infants with RSV seems
very low
– Full sepsis evaluations probably not needed
– Urine should be examined
22
Management:
Young Infants with RSV
• Levine, et al. Pediatrics 2004
– 3 year, multicenter, prospective cross –
sectional study
– T >38°C, age < 60d
– RSV from nasal swabs, urine, blood,
CSF, stool culture
– Yale Observation Score
– Looked for signs and symptoms of
bronchiolitis
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Management:
Young Infants with RSV
• Results
– 1248 patients
• 269 (22%) with RSV
• SBI 11.4% overall
– Rate of SBI:
• RSV negative
12.5%
• RSV positive 7.0%
– Bacteremia if RSV (+) 1.1%
– No patient with RSV had meningitis
• RSV negative
• RSV positive
UTI 10.1%
UTI 5.4%
– Prevalence of SBI is less in infants with RSV
but SBIs are present, especially UTI
– Levine, et al. 2004
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Management:
Young Infants with Influenza
• Krief WI, et al. Pediatrics 2009
– 3 year, multicenter, prospective cross –
sectional study
– T >38°C, age < 60d
– Influenza by rapid antigen detection and
urine, blood, CSF, stool culture
– Yale Observation Score
• Results
– Lower prevalence of SBI (2.5% vs.
13.8%) and UTI (2.4% vs. 10.8%) in
children with influenza
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Fever in Children
3 – 36 Months of Age
• Cause usually found with a thorough
history and physical.
• Most common diagnosis: viral URI.
• Other common causes: other viral illness,
otitis, UTI, streptococcal pharyngitis,
adenitis, cellulitis, pneumonia
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Toxicity
• Clinical picture consistent with sepsis syndrome
(lethargy, poor perfusion, hypo- or hyperventilation,
marked irritability or cyanosis).
• Lethargy – poor or absent eye contact, failure to
recognize parents or interact with the environment.
• ALL febrile children who are toxic appearing
should be hospitalized for evaluation and treatment
of possible sepsis and/or meningitis with parenteral
antibiotics.
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Fever in Children
2 – 6 months old (57 – 180d)
• Hsiao, HL. Pediatrics 2006
– Prospective study of patients 57 – 180 d, T > 37.9°C;
faculty member performed YOS
– CBC, CRP, Blood culture, U/A, urine culture,
respiratory pathogens; CXR and LP at MD discretion
• Results
– 429/448 (96%) eligible patients enrolled
– 44/429 (10.3%) with SBI:
• 41 bacteruria
• 4 bacteremia (1 with E. coli and bacteruria)
• 3/4 normal YOS
–
–
–
–
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0/58 LP positive for bacterial meningitis (7 pleocytosis)
SBI in 4.9% of patients with confirmed viral infection
WBC, ANC and CRP increased in patients with SBI
SBI common in this age group but mostly UTI
Occult Bacteremia
• 4% of children brought to an urban, “walk – in”
clinic with a T of > 38.3°C and no source of
infection had unsuspected bacteremia.
– McGowan, et al. New Engl J Med 1973
• Similar rates found in other settings.
• These children were well appearing.
• Definition: a positive blood culture in a well
appearing febrile child.
• This informed the approach to febrile infants
and toddlers for the last 30+ years
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Occult Bacteremia:
Bacteriology - Traditional
% of Bacteremia
patients
% that develop
invasive infection
S. Pneumoniae
50 – 60
4–5
H. Influenzae type B
20 – 30
20 – 50
N. meningitidis
10 – 20
25
Bacteria
30
Occult Bacteremia – Epidemiology:
Height of Fever
Height of Fever
% with bacteremia
> 39.4
> 40.0
> 40.5
> 41.1
3
6
13
26*
*Avner, Contemp Pediatr 1997
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Occult Bacteremia:
Effect of otitis media
• There is no difference in the prevalence
of bacteremia based on the presence or
absence of otitis media.
• Schutzman, et al. Pediatrics 1991
• There may be a decreased risk of
invasive disease.
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Occult Bacteremia Bacteriology:
That was then, this is now…
• > 90% S. pneumoniae
– 149 pathogens:100 contaminants
• Rate of bacteremia 1.5%
• No H. influenzae type B
– Lee, et al. Arch Pediatr Adol Med 1998
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Occult Bacteremia Bacteriology:
That was then, this is now…
• 1.9% bacteremia
• Approximately equal numbers of
contaminants and pathogens
• No H. influenzae type B
• Time to positive culture
– Pathogens
14.9h
– Contaminants 31.1h
– Culture that is positive in < 18h is thirteen
times more likely to be a true pathogen
» Alpern, et al. Pediatrics 2000.
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Occult Bacteremia Bacteriology:
That was then, this is now…
• Widespread conjugate pneumococcal
vaccine – rate of occult pneumococcal
bacteremia < 1%
• Stoll, et al. 2004
• Herz, et al. 2006
• Carstairs, et al. 2007
• Marked decrease in invasive disease
• Kaplan, et al. 2004
• Kyaw, et al. 2006
• Peters, et al. 2007
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Patients at increased risk:
Immunodeficiency
• Sickle cell disease
• Splenectomy (ITP, Hodgkin’s, hereditary
red cell defects, trauma)
• HIV
• Congenital immunodeficiencies
• In – dwelling devices
• Chemotherapy
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Occult Bacteremia:
Laboratory
• WBC of < 10K has a NPV of 99.2%
• WBC of > 15K increases the prevalence of
bacteremia to 10%
• ANC of > 10K is the best single predictor
• Kupperman, et al. Ann Emerg Med 1997
• ESR and CRP are roughly equivalent and less
available
• However, with such low prevalence, PPV of
WBC > 15K is only 1.5 – 3.2%
• Stoll, 2004 and Herz, 2006
37
Occult Bacteremia:
Outcome
• Before 1990:
– Untreated, 7% of patients could be
expected to acquire meningitis in older
studies.
– Up to 20% of patients would acquire
some invasive disease.
• Pathogen dependent!
• H. influenzae type B was the real
problem
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Occult Bacteremia:
Presumptive Therapy
• Oral amoxicillin no better than placebo at
preventing complications of occult
bacteremia
– Jaffe, et al. N Engl J Med 1987
• Similar results with several other agents
• Meta – analysis suggests slight benefit
for invasive complications except
meningitis
– Rothrock, et al. Pediatrics 2000
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Occult Bacteremia:
Presumptive Therapy
• Fleisher, et al. J Pediatr 1994
– 6,733 patients
• 192 with positive blood culture
–
–
–
–
–
Age 3 – 36 months
T > 39°C
Otitis media or no focal findings
All had blood cultures
Randomized to receive oral amoxicillin or IM
ceftriaxone
• 101 with positive blood culture received CTX
• 91 with positive blood culture received amoxicillin
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Occult Bacteremia:
Presumptive Therapy
Invasive Infections in Children Following
Bacteremia – Interpretation 1
Infection
41
Ceftriaxone
Amoxicillin
Meningitis
2*
3+
Pneumonia
---
1
Sepsis
---
1
Osteomyelitis
1
---
Arthritis
---
1
Total
3
6
Occult Bacteremia:
Presumptive Therapy
Invasive Infections in Children Following
Bacteremia – Interpretation 2
Infection
42
Ceftriaxone
Amoxicillin
Meningitis*
4
2
Pneumonia
---
1
Sepsis
---
1
Osteomyelitis
1
---
Arthritis
---
1
Sinusitis*
1
---
Preseptal cellulitis*
1
---
Total
7
5
Occult Bacteremia:
Proposed Approach
• Meta – analysis and expert panel
• Included Fleisher’s results
• T > 39°C, nontoxic appearance
–
–
–
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Urine culture: males < 6 mo; females < 2 y
CXR and stool culture if indicated
Option 1: Blood culture and CTX all children
Option 2: Blood culture and CTX if WBC > 15K
– Baraff LJ, et al. Ann Emerg Med, 1993
43
Occult Bacteremia:
Problems with Presumptive Therapy
• Less thoughtful approach to febrile
patients
• Potential adverse reactions
• Treating large numbers of nonbacteremic
patients
• Problems with contaminated cultures
• Decreases reliability of subsequent
studies
• Loss of clinical tools at reassessment
• Antibiotic resistance!
44
Occult Bacteremia:
Positive Blood Cultures
• Recheck all patients
• Management depends on:
–
–
–
–
–
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Organism
Treatment at original visit
Age of patient
Persistence of fever
Clinical appearance
Occult Bacteremia:
Pneumococcal Vaccine
• Impact of heptavalent conjugate
pneumococcal vaccine:
– 97% of OB isolates covered; decreased OB at
least 90%
– Children presenting with fever and no source:
• 0.3% will develop significant sequelae
• Only 0.03% will develop meningitis
– Cost – effectiveness of approach depends on
rate of bacteremia:
• 1.5 – 2.0% - CBC and selectively sending a blood
culture/treating is the most cost – effective strategy
• 0.5% (about where we are), observation alone clearly
becomes the most cost – effective
– New vaccine covering 13 serotypes now
licensed and in use – what effect will this have?
46
Warning Signs Recently Seen
• Rates of pneumococcal meningitis
decreasing but increasing number of
cases caused by serotypes not in the
heptavalent vaccine.
• Hsu HE, et al. N Engl J Med 2009
• Recent outbreaks of invasive H.
influenzae Type B disease.
• Rainbow J, et al. MMWR 2009
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Fever Without a Source:
Urinary Tract Infections
• High rate of urinary tract abnormalities in
young children with UTI.
• Fever and UTI in young children
indicates the presence of upper tract
disease.
• Case fatality rate of febrile UTI in young
children in 1930: 33%.
• Renal scarring increases by 33% for
every day of fever before antibiotics are
started in children with UTI.
48
Fever Without a Source:
Urinary Tract Infections
• Shaw, et al. Pediatrics 1998:
– 1560 patients with T > 38°C
• 82% of all children < 1 y
• 82% of all females < 2 y
– Bladder catherization for urine culture
– Blood culture in all patients < 3 mo and all
patients 6 – 24 mo with T > 39°C
– Positive urine culture defined > 104 CFU/ml
49
Urinary Tract Infections
Results – Shaw, 1998
UTI – all patients
UTI – Caucasian females
50
% (with 95% CI)
3.1
(2.3, 4.1)
17.9 (10.6, 25.2)
Males
1.5
(0.7, 2.8)
Age 6 – 24 mo, T > 39°C
Bacteremia
2.5
0.3
(1.6, 3,8)
(0, 1.0)
Fever Without a Source:
Urinary Tract Infections
• Hoberman had similar results in an
office – based study.
• Hoberman A, et al. Pediatr Infect Dis J 1997
• Prevalence of UTI not affected by
diagnosis of OM
• Possible biologic explanation for high
rates in Caucasian females.
• Best diagnostic tool a combination of the
UA and urine Gram’s stain.
51
Febrile Seizures
• Children with simple febrile convulsions have rates
of bacteremia similar to those with only fever.
• A simple, self – limited, febrile seizure alone is not
indicative of meningitis, even in young children (6 –
18 mo.)
– Green SM, et al. Pediatrics 1993
– Kimia AA, et al. Pediatrics 2009
• Lethargy is a better predictor of meningitis than
seizure.
• Even isolated complex seizures rarely associated
with acute bacterial meningitis
– Kimia A, et al. Pediatrics 2010
• AAP Guideline for Evaluation of SFS
– Subcomm. of Febrile Seizures, Pediatrics 2011
52
The Febrile Child 3 – 36 Months of
Age: A 21st Century Approach
• T > 39°C, no source or otitis media:
– UA, GS and urine culture all females and all
males < 6 months (1 y ?)
– CBC and CXR based on clinical judgment
– Blood culture if T > 40° (in the ED)?
– Treat only known, focal infections
• Role of practice setting
• Good follow – up is the most important part of
management
53
Fever in Infants and Young
Children: Summary
• “Unfortunately, many practitioners have
become reluctant to rely on clinical
judgment, preferring diagnostic tests and
frequent use of antibiotics…. We should
resist the urge to use antibiotics
empirically, especially in a patient who
looks well, for whom antibiotics have not
been shown clearly to be beneficial.”
– Stamos JK, Shulman ST. Lancet 1997
54
Fever in Infants and Young
Children: Summary
 “Antibiotics are
not
antipyretics.”
 Krug SE. SAEM
2002
Thank you!
55
References
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Albanyan EA, Baker CJ. Is lumbar puncture necessary to exclude
meningitis in neonates and young infants: lessons from the group B
streptococcus cellulitis-adenitis syndrome. Pediatrics 1998; 102:984-6.
Alpern ER, Alessandrini EA, Bell LM, Shaw KN, McGowan KL. Occult
bacteremia from a pediatric emergency department: current prevalence,
time to detection and outcome. Pediatrics 2000; 106:505-511.
Alpern ER, Alessandrini EA, McGowan KL, Bell LM, Shaw KN.
Serotype prevalence of occult pneumococcal bacteremia. Pediatrics
2001; 108:e23.
American Academy of Pediatrics, Committee on Infectious Diseases.
Therapy for children with invasive pneumococcal infections. Pediatrics
1997; 100:289-99.
American College of Emergency Physicians Clinical Policies Committee
and the Clinical Policies Subcommittee on Pediatric Fever. Clinical
policy for children younger than three years presenting to the emergency
department with fever. Ann Emerg Med 2003;42:530-545.
Avner JR. Occult bacteremia: how great is the risk? Contemp Pediatr
1997; 14:53-65.
Baker MD, Bell, LM, Avner JR. Outpatient management without
antibiotics of fever in selected infants. N Engl J Med 1993;329:1437-41.
Baraff LJ, Bass JW, Fleisher GR et al. Practice guidelines for the
management of infants and children 0 to 36 months of age with fever
without source. Ann Emerg Med 1993;22:1198-1210.
Baraff LJ. Management of fever without source in infants and children.
Ann Emerg Med 2000;36:602-614.
References
•
•
•
•
•
•
•
•
57
Baraff LJ. Editorial: Clinical policy for children younger than three years
presenting to the emergency department with fever. Ann Emerg Med
2003;42:546-549.
Baskin MN, O’Rourke EK, Fleisher GR. Outpatient treatment of febrile
infants 28 to 89 days of age with intramuscular administration of
ceftriaxone. J Pediatr 1992;120:22-7.
Bonadio WA, Hagenbarth M, Zachariason M. Correlating reported fever
in young infants with subsequent temperature patterns and rate of
serious bacterial infections. Pediatr Infect Dis J 1990;9:158-60.
Bonsu BK, Harper MB. Utility of the peripheral white blood cell count for
identifying sick young infants who need lumbar puncture. Ann Emerg
Med 2003;41:206-214.
Carstairs K, Tasnen D, Johnson S, et al. Pneumococcal bacteremia in
febrile infants presenting to the emergency department before and after
introduction of the heptavalent pneumococcal vaccine. Ann Emerg Med
2007;49:772-777.
Finklestein JA, et al. Pediatrics 2000; 105:260-266.
Fleisher GR, Rosenberg N, Vinci R et al. Intramuscular versus oral
antibiotic therapy for the prevention of meningitis and other bacterial
sequelae in young, febrile children at risk for occult bacteremia. J
Pediatr 1994;124:504-12.
Green SM, Rothrock SG, Clem KJ, Zurcher RF, Mellick L. Can seizures
be the sole manifestation of meningitis in febrile children? Pediatrics
1993;92:527-534.
References
•
•
•
•
•
•
•
•
•
58
Herz AM, Greenhow TL, Alcantara J, et al. Changing epidemiology of
outpatient bacteremia in 3 to 36 month-old children after the introduction
of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis
J 2006;25:293-300.
Hoberman A, Wald ER. Urinary tract infections in young febrile children.
Pediatr Infect Dis J 1997; 16:11-7.
Hsiao AL, Chen L, Baker MD. Incidence and predictors of serious
bacterial infections among 57- to 180-day-old infants. Pediatrics
2006;117:1695-1701.
Hsu HE, Shutt KA, Moore MR, et al. Effect of pneumococcal conjugate
vaccine on pneumococcal meningitis. N Engl J Med 2009;360:244-256.
Isaacman DJ, Shults J, Gross TK, Davis PH, Harper M. Prediction of
bacteremia in febrile children 3 – 36 months of age. Pediatrics 2000;
106:997-982.
Jaffe DM, Tauz RR, Davis AT et al. Antibiotic administration to treat
possible occult bacteremia in febrile children. N Engl J Med
1987;317:1175-80.
Joffe MD, Alpern ER. Occult pneumococcal bacteremia: a review.
Pediatr Emerg Care 2010;26:448-457.
Kaplan SL, Mason EO Jr, Wald ER, et al. Decrease of invasive
pneumococcal infections in children among 8 children’s hospitals in the
United States after the introduction of the 7-valent pneumococcal
conjugate vaccine. Pediatrics 2004;113:443-449.
Kimia AA, Carpraro AJ, Hummel D, et al. Utility of lumbar puncture for
first simple febrile seizure among children 6 to 18 months of age.
Pediatrics 2009;123:6-12.
References
•
•
•
•
•
•
•
•
59
Kimia A, Pearl Ben-Joseph E, Rudloe T, et al. Yield of lumbar puncture
among children who present with their first complex febrile seizure.
Pediatrics 2010;126:62-69.
Krief WI, Levine DA, Platt SL, et al. Influenza virus infection and the risk
of serious bacterial infections in young febrile infants. Pediatrics
2009;124:30-39.
Kupperman N, Fleisher GR, Jaffe DM. Predictors of occult
Pneumococcal bacteremia in young febrile children. Ann Emerg Med
1998; 31:679-86.
Kyaw MH, Lynfield R, Schaffner W, et al. Active Bacterial Core
Surveillance of the Emerging Infections Program Network. Effect of
introduction of the pneumococcal conjugate vaccine on drug-resistant
Streptococcus pneumoniae. N Engl J Med2006;354:1455-1463.
Lee GM, Harper MB. Risk of bacteremia for febrile children in the postHaemophilus influenzae type b era. Arch Pediatr Adolesc Med 1998;
152:624-8.
Lee GM, Fleisher GR, Harper MB. Management of febrile children in the
age of the conjugate pneumococcal vaccine: a cost-effectiveness
analysis. Pediatrics 2001;108:835-844.
Levine DA, Platt SL, Dayan PS, et al. Risk of serious bacterial infection
in young febrile infants with respiratory syncytial virus infections.
Pediatrics 2004;113:1728 – 1734.
Long SS. Antibiotic therapy in febrile children: “Best-laid schemes...” J
Pediatr 1994;124:585-8.
References
•
•
•
•
•
•
•
•
•
60
McCarthy PL, Lembo RM, Baron MA et al. Predictive value of abnormal
physical examination findings in ill-appearing and well-appearing febrile
children. Pediatr 1985;76:147-71.
McCarthy PL, Sharpe MR, Spiesel SZ et al. Observation scales to
identify serious illnesses in febrile children. Pediatr 1982;70:802-9.
McGowan JE Jr, Bratton L, Klein JO, Finland M. Bacteremia in febrile
children seen in a “walk-in” pediatric clinic. N Engl J Med
1973;288:1309-13.
McGowan KL, Foster JA, Coffin SE. Outpatient pediatric blood cultures:
time to positivity. Pediatrics 2000;106:251-255.
Rainbow J, Danila R, Bahta L, et al. Invasive Haemophilus influenzae
Type B disease in five young children – Minnesota 2008. Morbid Mortal
Weekly Rep 2009;58:58-60.
Shah SS, Alpern ER, Zwerling L, Reid JR, et al. Low risk of bacteremia
in children with febrile seizures. Arch Pediatr Adolesc Med
2002;156:469-472.
Shaw KN, Gorelick MH, McGowan KL et al. Prevalence of urinary tract
infection and occult bacteremia in febrile young children in the
emergency department (abstract). Presented at the Ambulatory
Pediatric Association meetings, Washington DC. 1996.
Schutzman SA, Petrychi S, Fleisher GR. Bacteremia with otitis media.
Pediatr 1991;87:48-53.
Stoll ML, Rubin LG. Incidence of occult bacteremia among highly febrile
young children in the era of the pneumococcal conjugate vaccine. Arch
Pediatr Adolesc Med 2004;158:671-675.
References
•
•
•
•
•
•
61
Subcommittee on Febrile Seizures. Febrile seizures: guideline for the
neurodiagnostic evaluation of a child with a simple febrile seizure.
Pediatrics 2011;127:389-394.
Sullivan JE, Farrar HC, et al. Clinical Report – fever and antipyretic use
in children. Pediatrics 2011;127:580-587.
Titus MO, Wright SW. Prevalence of serious bacterial infections in
febrile infants with respiratory syncytial virus infection. Pediatrics
2003;112:282-284.
Wald ER, Dashefsky B. Cautionary note on the use of empiric
ceftriaxone for suspected bacteremia. Am J Dis Child 1991;145:135961.
Warden CR, Zibulewsky J, Mace S, Gold C, Gausche – Hill M.
Evaluation and management of febrile seizures in the out – of – hospital
and emergency department settings. Ann Emerg Med 2003;41:215-222.
Yamamoto LG. Revising the decision analysis for febrile children at risk
for occult bacteremia in a future era of widespread pneumococcal
immunization. Clin Pediatr (Phila) 2001;40:583-594.