The Evaluation of Fever in the Infant and Child: Risk Factors and Management Robert J' Vinci, MD

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The Evaluation of Fever in the Infant and
ChildRisk Factors and ManagementRobert J.
Vinci, MD
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Objectives

• Review the epidemiology of SBI in infants
• Develop strategies for identifying infants at
  high risk for SBI
• Based on clinical data, develop treatment plan
  for infants suspected of having SBI
• Review the epidemiology of HSV infection in
  infants

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A six week old infant presents with a fever of
38.5oC. The child is alert and appears well
hydrated. The other vital signs are HR of 146,
RR of 52 and BP of 80/P. The remainder of the
exam is normal. The child had a normal neonatal
course and the pregnancy was uncomplicated.
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Febrile Infant

• Serious bacterial infection (SBI) occurs in
• 5 - 12 of infants, (lt 3 months of age) with a
  temp gt 100.6o F
• SBI
• Bacterial pathogen from blood, urine, stool or
  CSF
• Pulmonary infiltrate
• Infants with obvious cellulitis, abscess or
  arthritis
• Can you identify the child at risk for SBI?

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How can an experienced clinician identify the
infant at risk for SBI?

• Pregnancy history, especially group B strep
  status of mother. Early vs. Late Disease
• Neonatal course in-dwelling lines, respiratory
  support, antibiotic Rx
• Post-natal exposures to pathogens
• Any known risk factors for immunodeficiency
• Use of screening lab tests

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Some questions to consider?

• What diagnostic studies are indicated?
• Is the infant hospitalized?
• Do all infants with fever require treatment with
  antibiotics?

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Question 1What diagnostic studies are
indicated???
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(No Transcript)
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Diagnostic Studies

• CBC with blood culture
• Urinalysis and urine culture
• Stool for WBCs in patients with diarrhea
• Lumbar puncture in all infants
• Chest films only if symptoms, or abnormality on
  exam

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Low Risk Criteria

• History suggests no increased risk for infection
• Normal Physical exam
• WBC gt 5,000 and lt 15,000
• Bands lt 1,500 or BNR lt 0.2
• UA with lt 10 WBC/HPF
• If patient has diarrhea, stool gram stain reveals
  lt 5 WBC
• Normal lumbar puncture

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Performance of Screening CriteriaBaker, et.al.
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Performance of Screening CriteriaBaker, et.al.

• Sens. 64/65 98 (95 CI 92 100)
• PPV 64/460 14 (95 CI 11-17)
• Spec 286/682 42 (95 CI 38-46
• NPV 286/287 gt 99 (95 CI 95-100)
• The one patient that was missed was an infant
  with bacteremia. That infant was well at 24
  hours of age when the bacteremia was diagnosed.
  He was identified by the modified screening
  criteria. (BNR of lt0.2)

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Question 2Is the infant who presents with
fever hospitalized???
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Cost of Hospitalizaion for Patients at Low Risk
for SBI

• Cost savings of approximately 3,400 per infant
• Less complications such as IV infiltrate and
  iatrogenic infections
• Less disruptive for the family.
• Could it lessen parental stress?

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Question 3 Do patients who meet the criteria
for Low-Risk for SBI need to be treated with
antibiotics??
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What treatment options?

• Parenteral Antibiotics
• Oral Antibiotics
• No Antibiotics

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Neonatal PathogensSadow, et.al.

• Total of 121 pathogens
• 96 were gram negative rods
• 60 were ampicillin resistant
• 14 were group B strep
• 7 were enterococcus
• 3 were strep pneumonia
• 1 was neisseria meningitidis

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Performance of Screening Criteria
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Treatment Options

• Patient ill-appearing or high risk for SBI
• IV Antibiotics
• Ampicillin and gentamicin
• Ampicillin and cefotaxime
• 3rd generation cephalosporin, only. Will not
  cover enterococcus and Listeria.
• Patient low risk for SBI
• No antibiotics
• IM ceftriaxone

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Question 4Are the Screening Criteria
Applicable for All Ages?????
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Performance of Screening Criteria Infants lt 4
weeks of age
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Screening CriteriaInfants lt 4 weeks of age

• 109 met criteria for low risk
• 5 of these infants had significant bacterial
  infection
• The negative predictive value is only 95

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Infants at Low Risk for SBI
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Chest Radiographs in Febrile Infants

• Not routinely indicated unless
• Respiratory symptoms
• Cyanosis
• Focal pulmonary exam findings
• Unexplained tachypnea
• Elevated WBC gt 20,000

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Question 5Can we afford to label all culture
negative infants as having a viral infection?
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Enteroviral Infections

• All enteroviruses share common genomic sequences,
  which can be amplified using a single set of PCR
  primers.
• Thus, earlier diagnosis of enteroviral infections
  is now possible

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What is the benefit of diagnosing an infant with
an enteroviral infection?
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Enteroviral Infections - Treatment

• Early discharge from the acute care setting.
  Less antibiotic use and and decreased cost of
  hospitalization
• Other Treatment Options
• IVIG prevents viral binding to specific target
  receptors. May be indicated in enteroviral
  sepsis
• Interferon therapy
• Pleconaril Antiviral agent which prevents
  attachment to host cell receptors

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Question 6In which infants do we need to
consider therapy against Herpes Infections??
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HSV Maternal Infection

• Using type-specific antibodies against HSV 2,
  about 20 of pregnant women have had HSV 2
  infection.
• Majority of these women have no evidence of
  primary or recurrent infections
• Viral excretion at time of delivery is 0.01 to
  0.39. It increases to 0.2 to 7.4 with history
  of known genital herpes

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HSV Maternal Infection

• What does it all mean for clinicians??
• The most important fact about maternal
  transmission is that most infants who develop
  neonatal disease are born to women who are
  completely asymptomatic during the pregnancy as
  well as at the time of delivery

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HSV Newborn Infection

• Occurs in 12000 to 15000 live births
• Intrapartum acquisition is most common in utero
  and post-partum occur
• Neonatal infections are almost invariably
  symptomatic

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HSV Newborn Infection

• Three classifications of infection
• Localized to skin, eyes or mouth
• CNS infection with or without mucocutaneous
  lesions
• Disseminated infection involving multiple organs
• These infections may present after first week of
  life, and encephalitis may present as late as 4
  6 weeks of life.

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HSV High Risk

• History of active herpes in mother
• Unexplained vesicular rash in infants
• CNS deterioration, especially seizures
• Disseminated disease
• Hemorrhagic CNS findings (minority of children
  with encephalitis)
• Send PCR analysis, begin Acyclovir
• 20 mg/kg/dose TID for 21 days

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Conclusion The Febrile Infant

• All infants require a complete medical and
  laboratory evaluation
• Screening criteria can be used to identify
  Low-risk infants who can be managed at home,
  possibly without antibiotics
• Infants 0 28 days of age still require
  hospitalization, regardless of results of
  screening tests
• Always consider HSV infections in high risk
  infants

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Bacteremia inChildren
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Objectives

• Review epidemiology of bactermia in febrile
  children
• Discuss indications for laboratory evaluation of
  febrile children
• Understand the impact of conjugated pneumococcal
  vaccine in the management of febrile children
• Review treatment options for febrile children

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• An eighteen month old child presents to the ED
  with a temp of 39.5oC. Upon arrival the child is
  noted to be irritable but does calm when held by
  the parents. Vitals are otherwise normal. The
  child has a runny nose and a red right tympanic
  membrane. What work-up, if any is indicated in
  this child???

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Bacteremia Scope of the Problem

• 2 - 3 of febrile children
• Age 3 - 36 months
• How to identify the at risk child
• Significant morbidity from complications
• Meningitis
• Septic Arthritis

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Multicenter Bacteremia TrialFleisher et.al.

• 6,700 febrile children enrolled
• Ages 3 36 months
• Oral amoxicillin vs. IM Ceftriaxone
• 3 rate of bacteremia

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Multicenter Bacteremia TrialFleisher et.al.

• Only five patients had persistent positive
  cultures
• All five patients were in the amoxicillin
  treatment group

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Major Complications

• 3 patients with meningitis (H.flu x 2,
  S.pneumonia x 1)
• 1 patient with pneumonia (S.pneumonia
• 1 patient with persistent bacteremia
  (S.pneumonia)

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Conclusions

• Ceftriaxone lessens the risk of significant
  complications, although not to a significant
  degreee when compared to amoxicillin
• Ceftriaxone eradicates bacteremia in all cases
• Lower incidence of complications in the entire
  study group
• Changing epidemiology of occult bacteremia

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Etiology of Bacteremia 2002

• S. Pneumonia
• S. Enteritidis
• N. Meningitidis
• Group A Strep
• Other organisms

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What diagnostic studies are indicated in this age
group?

• None
• Urine Assays
• CBC/Blood Culture
• Spinal Fluid Analysis
• Chest X-ray

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Lets do the easy ones, first!!
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Urine Cultures in Febrile ChildrenBauchner,
et.al.
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What does it mean?

• Urine cultures will be positive in 5 10 of
  febrile children
• Girls 0 24 months of age
• Boys 0 6 months of age
• May increase age limit in uncircumcised boys
• No urine bag cultures

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Chest Radiographs in Febrile Children

• Not routinely indicated unless
• Respiratory symptoms
• Cyanosis
• Focal pulmonary exam findings
• Unexplained tachypnea
• Elevated WBC gt 20,000

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Lumbar Puncture in Febrile Children??

• Children with presumed meningitis
• Sick Children
• Patients with persistent fever who are known to
  be bacteremic
• ?? Febrile Seizures

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Fever Reduction and the Severity of Disease

• Response to antipyretics does not predict
  bacteremia
• Degree or rapidity of temperature decline does
  not predict bacteremia
• An inadequate response to an antipyretic may
  indicate serious infection

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The Patient with a positive blood culture

• All patients should return for repeat evaluation
• If afebrile and well appearing can continue to be
  managed at home with antibiotics
• If febrile or sick should be worked up and
  admitted

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Fever with Known Viral Disease

• Decreased incidence of bacteremia and urinary
  tract infections in infants with a clinical
  diagnosis of definite viral disease such as
• Varicella
• Herpes Gingivostomatitis
• Hand-Foot-Mouth Disease

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What about the use of blood cultures?

• Sick Children
• Children with immunodeficiency
• HIV
• Sickle Cell Disease
• Extreme pyrexia (temps gt 104o
• What about vaccine status of child?

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Pneumococcal Heptavalent Vaccine (Prevnar)

• 7 types are consistently responsible for invasive
  disease (70 - 90)
• Otitis media is the exception
• Resistance is most common in these 7 phage types

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Prevnar Efficacy

• 97 Fully vaccinated
• 94 Partial Vaccinated
• 89.1 All pneumococcal serotypes
• 86 Two dose schedule

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Pneumococcal VaccineClinical Effectiveness

• 89 reduction of invasive disease
• 8.9 reduction in otitis media visits
• 20 reduction in ventilatory tube placements
• No serious adverse reactions
• Early data suggests there may be herd immunity in
  older children

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Prevnar Vaccine
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What do we do with this data?

• Child with fever who looks well
• Has received at least 3 doses of Prevnar
• Careful clinical evaluation may be reasonable
  approach without the use of diagnostic studies
  except for urine cultures in at-risk infants
• If not, CBC and Blood culture for fever.
  Consider Ceftriaxone for those with high WBC or
  concerning exam

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What treatment options?

• Ceftriaxone
• Oral Antibiotics
• No Antibiotics
• Admission is reserved for the acutely ill child
  or the child with persistent bacteremia and fever

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Summary

• Bacteremia remains a perplexing problem
• Studies which evaluate whether presumptive
  antibiotic therapy lessens the risk of
  complications are not overwhelming
• New vaccines hold great promise and may impact on
  our approach to the management of young febrile
  children