Fever in Infants and Children: Sepsis, Meningitis, and Occult Bacteremia

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Fever in Infants and ChildrenSepsis,
Meningitis, and Occult Bacteremia

• Rashmi Srivastava, MD
• Department of Child Health

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Fever Phobia

• Fever is the most common pediatric complaint,
  second only to routine care for clinic visits,
  and the most common reason kids are brought to
  the ER.
• In the Middle Ages, fever was felt to be a marker
  of death or divine punishment.
• Some feel true fever is harmful 1/3 parents
  thought 38-40ºC(100.4-104ºF), 2/3
  40-41ºC(104-106ºF), and all thought brain damage
  gt41ºC(106ºF).
• 5-20 have no localizing signs on PE with no
  history to explain the fever.
• The majority of kids with fever do not have a
  serious illness, although a small percentage
  harbor or may develop a serious bacterial
  infection.

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True Fever

• Occurs when IL-1, IL-6, TNF-? or other cytokines
  are released from monocytes and macrophages in
  response to infection, tissue injury, drugs, and
  other inflammatory processes, increasing the
  bodys set point. The anterior hypothalamus
  maintains an inherent set point near
  36ºC(98.6ºF).
• Normal circadian rhythm, which is highest(up to
  2ºC, 3ºF) 6pm and lowest at 6am. This accounts
  for increased volume of ER visits that peaks in
  the evening. Most true fevers follow this
  diurnal pattern.

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False fever, aka hyperthermia

• Does not directly increase the bodys set point.
• CNS disease that directly affects the
  hypothalamus--ICH, infection.
• Diseases that increase the bodys production of
  heat--hyperthyroidism, malignant hyperthermia,
  salicylate overdose.
• Excess heat load--child left in a car or left
  next to a heater for too long.
• Defective heat loss mechanisms--burns, heat
  stroke, drugs that compromise blood flow and
  sweating mechanisms.
• Normal causes of temperature elevation include
  physical activity, ovulation, and environmental
  temperature.

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Reliable Temperature Measurement

• All measurements are estimates of the bodys true
  core tempcentral circulationaorta and pulmonary
  artery.
• RECTALgold standard
• Esophagealaccurate but impractical
• Tactile and axillaryinaccurate, varies
  considerably with environmental temperature
• Tympanicinaccurate in age lt3 years

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Benefits of fever

• The hypothalamus will not allow the temp to rise
  above 41.5ºC(107ºF).
• WBCs work best and kill the most bacteria at
  38-40ºC(100.4-104ºF).
• Neutrophils make more superoxide anion, and there
  is more and increased activity of interferon.
• Coxsackie and polio virus replication is directly
  inhibited.

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Diagnostic Assessment in Children

• Age is important as 1) etiologic pathogens, 2)
  clinical exam, and 3) immune system capacity
  changes as the newborn ages.
• Most break them into the first 2-4 weeks of
  life(neonatal), 1-3 months, and 3 to 36 months.

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Neonatal

• PE is felt to be unreliable in detecting many
  serious bacterial infections. Meningitis should
  always be consideredup to 10 appear well, only
  15 have a bulging fontanelle, and 10-15 have
  nuchal rigidity. So, a high index of suspicion
  is important!!! 20 will not have fever
  initially.
• Hyperthermia or hypothermia
• Lethargy or irritability
• Poor feeding or vomiting
• Apnea
• Dyspnea
• Jaundice
• Hypotension
• Diarrhea or abdominal distension
• Bulging fontanelle
• seizures

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Neonatal
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Neonatal

• Risk Factors
• Preterm
• Membrane rupture before labor onset or
  prolongedgt12 hours
• Chorioamnionitis or maternal peripartum fever
• UTI
• Multiple pregnancy
• Hypoxia or Apgar score lt6
• Poverty or age lt20
• 1/3-1/2 neonatal sepsis will have no risk factors!

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Neonatal

• Screening tests WBClt5000 or gt20,000, PMN lt4000,
  ITgt.2, Pltlt100,000, CRPgt1, LFTs elevated(suggest
  HSV)
• So, if lt28 days of age and rectal tempgt 38ºC
• Admit
• Blood Culture
• Urine Cultureoptional if lt7 days
• Lumbar Puncture
• Cell count, protein, glucose, culture, PCR
• Parenteral Antibiotics
• Ampicillin Gentamicin(Cefotaxime), Acyclovir?

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Infants 1 to 3 months

• Causes
• HSV(17 are 15 days to 6 weeks of age)
• Bacterial sepsis/meningitis
• Group B Strep, S. Pneumoniae, H. influenza, N.
  meningitidis, Enterobacteriaceae
• Bone and joint infections
• UTI
• Bacterial enteritis(esp Salmonella)
• Pneumonia
• Enterovirus sepsis/meningitis(July-October)
• The risk of bacteremia/meningitis is 3.3,
  pneumonia, bone/joint infections and bacterial
  enteritis is 13.7
• 30-50 of those who are ultimately diagnosed with
  bacterial meningitis have been seen by a
  physician within the prior week(usually 1-2 days
  before) and were diagnosed as having a trivial
  illness and discharged on oral antibiotics.

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Infants 1 to 3 months

• Infants who are toxic and febrile have a much
  higher risk of serious bacterial infection. They
  should be admitted, have a full sepsis workup,
  and given antibiotics/antivirals?Ampicillin and
  Cefotaxime.
• Infants who are nontoxic and febrile who meet all
  Rochester criteria can safely be treated as an
  outpatient. Generally, 1-2.9 of children
  meeting these criteria will develop a serious
  bacterial infection, 0.7 bacteremia, 0.14
  meningitis.

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Infants 1 to 3 months

• Rochester Criteria/Low Risk Criteria
• Nontoxicmost critical and difficult
• Previously healthy, not low birth weight
• No focal bacterial infection on PE except Otitis
  Media
• WBC 5,000-15,000/mm3
• Bandslt1500/mm3
• Normal urinalysis, including gram stain
• If diarrhea, must be non-bloody and WBClt5/hpf.
• If respiratory symptoms present, normal CXR

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Infants 1 to 3 months

• If all of the criteria are met, then there are 2
  options for outpatient management
• 1) Blood, Urine Cultures, LP, Ceftriaxone
  50mg/kg IM (to 1g), and return for reevaluation
  within 24 hours.
• 2) Blood, Urine Cultures and careful
  observation.
• Parents should have mature judgement, can return
  within 30 minutes and have a thermometer and a
  phone.

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Infants 1 to 3 months

• Follow-up of low risk infants
• If all cultures negative afebrile, well
  appearing?Careful observation
• Blood cultures negative well appearing,
  febrile?Careful observation, may consider second
  dose of Ceftriaxone
• Blood culture positive?admit for sepsis workup
  and parenteral antibiotics pending results
• Urine culture positive if persistent
  fever?admit for sepsis workup, parenteral
  antibiotics pending results. If afebrile and
  well?outpatient antibiotics

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Infants 3 to 36 months

• Infant sepsis syndrome
• Age 3-36 months
• Fevergt39ºC
• ANCgt10,000
• If a child meets all 3 criteria, he has a 3 risk
  for pneumococcemia. If untreated, 3 will
  progress to meningitis.
• Bacteremia risk peaks at 8-12 months
• Pneumococcal sepsis peaks at 1 year, then drops
  off
• Pneumococcal meningitis peaks at 3-5 months
• OM, sinusitis, pneumonia, response to
  antipyretics, and social status do not
  significantly alter risk.
• Other causes HHV6(15), UTI(girls 3, boys
  0.6), menigococcemia(0.1), Salmonella(0.2), H.
  influenza(0.05), Enterovirus(July?October).

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Infants 3 to 36 months

• UA with micro, CBC with differential, Blood
  Cultures
• LP if meningeal signs, not wanting to be held or
  moved, petechiae, purpura or toxic.
• Antimicrobials
• OM or pneumonia cover for pneumococcus,
  non-typable H. flu and Moraxella
  amoxicillinaugmentin, ceftriaxone
• URI or no focus cover for pneumococcus and
  menigococcus amoxicillin(80-100mg/dg/day),
  ceftriaxone
• Pneumococcemia promptly reassess, if well,
  should at least treat with 1 dose ceftriaxone.
• PCV-7 gt97 protection, thus all pneumococcal
  sepsis will decrease by 90. So CBC and
  antimicrobials for this age group is becoming
  less critical.

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Fever without a source

• 5 to 20 of febrile children have no localizing
  signs on PE and nothing in the history to explain
  the fever. By definition, less than 7 days.
• FWS(like fever) is most common in children
  younger than age 5, with a peak prevalence
  between 6 and 24 months of age.
• Those lt6 months retain protective maternal
  antibodies against common organisms, while those
  18-24 months old are more immune competent, and
  are at a lower risk of developing bacteremia.
• 5 of children with FWS have OCCULT BACTEREMIA
• The presence of a positive blood culture in kids
  who look well enough to be treated as outpatients
  and in whom the positive results are not
  anticipated.

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Occult Bacteremia

• Streptococcus pneumonia is responsible for 2/3 to
  ¾ of all cases.
• Peak prevalence between 6 and 24 months
• Association with high fever(39.4ºC or 103ºF)
• High WBC count(gt15,000)
• Absence of evident focal soft tissue infection.
• Neisseria meningitidis, Haemophilus influenzae
  type b, and salmonellae account for most of the
  remaining cases.

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Risk of Occult Bacteremia

• OB has a low prevalence, so even though WBC is a
  sensitive and specific screening test, it has a
  low PPV. So the test does not discriminate
  between children who have FWS who are bacteremic
  and those who are not.
• Therefore, blood culture is the gold
  standard?still has a high number of false
  positives, take 24-48hrs, and most cases of
  occult pneumococcal bacteremia clear without
  treatment.

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Occult Bacteremia

• Empiric antibiotics should be targeted against S.
  pneumoniae, N. meningitidis, and H. influenza
• Amoxicillin
• Augmentin, Bactrim, 2nd or 3rd gen Cephalosporins
• Single dose Ceftriaxone 50-75mg/kg
• Followup is essential!

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• Oskis Pediatrics, 3rd edition
• Harriet Lane, 16th edition
• The Febrile Child. Emergency Medicine Reports.
  September 1995.
• Antibiotic Choices The critical first hour.
  Pediatric Annals. June 1996.
• Evidence based approach to the febrile
  infant/child. Handout from Dr. Michael
  Cooperstock, MD. May 2000.

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