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


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Title: The Evaluation of Fever in Infants: Risk Factors and Management Robert J' Vinci, MD

The Evaluation of Fever in Infants Risk Factors
and Management Robert J. Vinci, MD
  • Review the epidemiology of Serious Bacterial
    Infection (SBI) in infants
  • Develop strategies for identifying infants at
    highest risk for SBI
  • Review the epidemiology of HSV infection in
  • Based on clinical data, develop treatment plan
    for infants suspected of having SBI

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.
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
  • Pulmonary infiltrate
  • Infants with obvious cellulitis, abscess or
  • Can you identify the child at risk for SBI?

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

What are the Pathogens?
  • Pre-natal Infections
  • Acquired at the time of Delivery
  • Acquired after birth

Group B Strep Disease
  • Before prevention approximately 8,000 babies/year
    in the US
  • 5 mortality
  • 0.5 1 of babies infected if mom is Group B
    Strep positive
  • 75 of cases are early (1st week of life)
  • Risk factors
  • Maternal fever
  • PROM
  • Pre-term labor
  • Previous infant with Group B Strep

Group B Strep Disease
  • ACOG currently recommends screening of all women
    at 35 37 weeks
  • Treating women during labor who are known to be
    GBS positive will prevent 90 of early onset
    Group B Strep disease
  • Late-onset disease is not prevented by
    intrapartum administration of antibiotics

Some questions to consider?
  • What diagnostic studies are indicated?
  • Is the infant hospitalized?
  • Do all infants with fever require treatment with

Question 1 What diagnostic studies are
Rochester Criteria
  • Full Term Birth
  • Well appearing infant
  • Normal exam with no focal disease
  • WBC 5000 15,000
  • Bands lt 1500
  • If Diarrhea, no WBCs in stool
  • lt 10 WBCs on urinalysis

Rochester Criteria
  • A 1992 meta-analysis of 14 studies of febrile
    infants found that infants who were classified as
    low-risk had an occurrence of SBI of 1.4,
    whereas, those who were classified as high risk
    had an occurrence of SBI of 21
  • Baraff LJ,, Peds Infect Dis J.

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

Philadelphia 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

Performance of Screening Criteria Baker,
(NEJOM 19933291437-1441
Performance of Screening Criteria Baker,
  • 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)

Question 2 Is the infant who presents with
fever hospitalized???
Cost of Hospitalization 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?

Question 3 Do patients who meet the criteria
for Low-Risk for SBI need to be treated with
What treatment options?
  • Parenteral Antibiotics
  • Oral Antibiotics
  • No Antibiotics

Neonatal Pathogens Sadow,
  • 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

Performance of Screening Criteria
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

Question 4 Are the Screening Criteria
Applicable for All Ages?????
Performance of Screening Criteria Infants lt 4
weeks of age
Screening Criteria Infants lt 4 weeks of age
  • 109 met criteria for low risk
  • 5 of these infants had significant bacterial
  • The negative predictive value is only 95

Infants at Low Risk for SBI
Chest Radiographs in Febrile Infants
  • Not routinely indicated unless
  • Respiratory symptoms
  • Cyanosis
  • Focal pulmonary exam findings
  • Unexplained tachypnea
  • Elevated WBC gt 20,000

Question 5 Can we afford to label all culture
negative infants as having a viral infection?
Enteroviral Infections
  • All enteroviruses share common genomic sequences,
    which can be amplified using a single set of PCR
  • Thus, earlier diagnosis of enteroviral infections
    is now possible

What is the benefit of diagnosing an infant with
an enteroviral infection?
Enteroviral Infections - Treatment
  • Early discharge from the acute care setting.
    Less antibiotic use and and decreased cost of
  • Other Treatment Options
  • IVIG prevents viral binding to specific target
    receptors. May be indicated in enteroviral
  • Interferon therapy
  • Pleconaril Antiviral agent which prevents
    attachment to host cell receptors

Question 6 In which infants do we need to
consider therapy against Herpes Infections??
HSV Maternal Infection
  • Using type-specific antibodies against HSV 2,
    about 20 of pregnant women have had HSV 2
  • 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

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

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

HSV Newborn Infection
  • Three classifications of infection
  • Localized to skin, eyes or mouth
  • CNS infection with or without mucocutaneous
  • 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.

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

Question 7 What is the impact of a known Viral
Impact of RSV Disease
  • Case Control study of 174 infants with RSV
  • 2/174 in RSV had an SBI
  • 22/174 in RSV had an SBI
  • Titus and Wright Pediatrics 2003112282-284

Impact of RSV Disease Levine,, Pediatrics
  • Multi-Center Trial of 1248 patients
  • 17/244 who were RSV had an SBI (7). 14 were
  • 116/925 who were RSV had an SBI (12.5)
  • NO child with RSV had meningitis
  • Rates of bacteremia were lower (1.1) in RSV
    patients compared to 2.3 in RSV - infants

Impact of all Viral Infections Byington,,
Pediatrics 20041131662-1666
  • 1385 infants over six year period.
  • Evaluated infants with fever according to the
    Rochester Protocol and compared infants with
    positive viral testing to those who were viral
  • Overall rate of SBI was 9.5

Rates of Infection
  • Rate of SBI was 21/491 (4.2) in infants with a
    viral infection
  • Rate of SBI was 110/894 (12.3) in infants with
    no viral infection
  • Five infants (1) with viral infections had
    bacteremia compared to 24 (2.7) of infants with
    no viral infection
  • No case of meningitis in infants with viral

Application of Rochester Criteria
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

Conclusion The Febrile Infant
  • The presence of known viral infections is
    associated with a lower risk of SB I
  • Urinary Tract infections are significant even in
    the setting of a known viral infection
  • No matter what strategy you choose, nothing is
    100 and careful follow-up is required