The Febrile Infant

Definition

• Infant <2-3 months old:
  • Fever = >38 degrees rectal temperature
• 3-36 month old
  • Concerning fever =>39 degrees
• >36 months
  • Concerning fever not defined as should show signs/symptoms of focus
• Acute fever = <7 days duration
• Since pneumococcal vaccination, occult bacteraemia rate <1% in healthy, immunised infants
• Height of fever makes no distinction of aetiology

Neonatal fever

• Neonates carry twice the risk of SBI as infants 4-8 weeks of age
  • Any infant <3 months of age is at higher risk
  • Reduced opsonin activity, decreased macrophage and neutrophil function and bone marrow exhaustion
  • Poor IgG response to encapsulated bacteria until 24 months of age
• Neonatal sepsis
  • Early-onset syndrome
    • First days of life, tends to be fulminant, and is usually associated with maternal or perinatal risk factors
    • Septic shock and neutropaenia more common
  • Late-onset syndrome
    • Usually after 1 week of age, more gradual onset, less likely to be associated with risk factors
    • Meningitis more common

Presenting symptoms in neonates

• Temperature instability
• CNS dysfunction
• Respiratory distress
• Feeding disturbance
• Jaundice
• Rash
• Lethargy
• Irritability
• Seizures
• Apnoea
• Grunting
• Vomiting, poor feeding, gastric distension and diarrhoea

Infants <3mo

• History
  • Review birthHx, peripartum antibiotics, meconium liquor, neonatal complications
• Examination
  • Complete head-to-toe including ENT for source

Infants 3-36 months old

• Clinical assessment more reliable
• Toxic infants will not respond appropriately
• Bacterial pharyngitis is unlikely under 3yo
• Typical signs of meningitis may be absent up to 2 years of age

Children >36 mo

• Typically have symptoms
• Pharyngitis due to GAS becomes more common
• Infectious mononucleosis also becomes more common
• Can use Centaur criteria for pharyngitis to determine Ab requirement
• Always consider Kawasaki disease

Decision rules

• Difficult to extrapolate results from original studies due to changes in vaccination and peripartum antibiotics for GBS-positive women
• Subsequent studies applying these rules missed SBI in neonates. Therefore not used in this cohort
• Rochester criteria
  • Least sensitive
  • Does not include LP in workup
  • Misses 1% of SBI
  • States that in well-appearing neonates and infants <60 days old, without prior or peripartum illness, normal FBC/urinalysis/CXR rules out SBI
• Philadelphia protocol
  • 29-56 day olds only including LP in decision-making
  • Low-risk criteria met: Sensitivity for excluding SBI 98%; Specificity 44%
  • Temp criterion 38.2 degrees
  • 1.2% meningitis incidence in study. None missed.
  • All bacteraemia and UTI identified
• Boston criteria
  • 28-89 days old. Accepted WCC up to 20 as normal
  • LP performed in all patients
  • Low-risk criteria met: <1% of patients had missed SBI and none had complication after empirical ceftriaxone

Investigations

• 1-3 months corrected age
  • FBC/film, BC, urine culture (SPA) +- CXR (if resp. symptoms or signs) +- LP
  • Discharge home with review within 12 hours if:
    • Previously healthy
    • Appears well
    • WCC 5-15
    • Urine microscopy clear
    • CXR clear (if done)
    • CSF clear (if done)

• >3 months
  • Clear focus: Treat accordingly
  • Unclear focus:
    • Looks well:
      • Boys <12 mo/girls <2yo: urine
      • Can do SPA up to 12mo
      • Discharge home
      • Symptomatic Rx and review in 24 hours
    • Miserable
      • Boys <12mo, Girls<2yo: Urine
      • D/W Senior
    • Unwell
      • FBC, BC, Urine culture +-CXR +-LP
      • Admit for observation +- Empirical Ab

Bacteraemia and sepsis

• Most studies cite bacteraemia rate 2-3% in febrile infants <3mo
• Most commonly E. coli, GBS, Listeria
• Ill-appearing infants with fever have rate as high as 13-21%
• Viral infections still most common
• The Hib and pneumococcal vaccines have reduced the bacteraemia rate in infants 3-36 months of age from 2-3% to 0.5-0.7%
• PCV7 protects against S. pneumoniae but NOT GBS
  • Received at 2, 4 and 6 months so may have only had one or none of these doses remember

Urinary tract infection

• Most common SBI
• 3-8% of young children with fever of unknown origin
• Overall incidence is 5% in children 2mo to 2yo
• In young children 1-2 yo: Girls 8% vs. Boys 1.9% incidence
• Uncircumcised boys have UTI rate 5-20x that of circumcised boys
• Fever >39 + urine suggestive of infection indicates renal parenchymal involvement and/or pyelonephritis

How to get a urine?

• Clean catch if possible
• If septic, SPA or catheter specimen may be required

How good is a urine dipstick?

• Positive leukocyte esterase:
  • Sensitivity 67%; Specificity 85%
• Positive nitrites
  • Specificity 95-99%
• Less reliable in children under 3yo
  • Always send for MCS anyway

Urine MCS

• Positive white cells = >5-10 WCC/HPF
  • Sensitivity 51-91%
• Bacteria on gram-stain
  • Sensitivity 80-97%; Specificity 87-99%
• Always consider BC and LP in children with suspected UTI
  • 5-10% of febrile infants with UTI have bacteraemia
  • Bacteraemia in up to 30% in infants 4-8 weeks of age
  • <1% of febrile infants with UTI will have bacterial meningitis but case reports exist
    • May have sterile pleiocytosis due to systemic inflammatory mediator release
    • Practice currently is admit for IV therapy and do LP later if concern for meningitis exists (unless <1mo then all get LP)

Pneumonia and sinusitis

• Sinusitis uncommon in children <3 years old (sinus formation incomplete)
• WCC >20 associated with occult pneumonia in 19% of cases (despite no clinical findings)
• Pneumonia in a febrile but otherwise asymptomatic child is unlikely

Meningitis

• Incidence of 1% in febrile infants <3mo
  • E. coli, GBS, Listeria
• If >3 months: S. pneumoniae, N. meningitidis, S. aureus
• CSF WCC >30 cells/mm3 in neonate and >10cells/mm3 in children >1mo suggest meningitis
• Risk factors for 29 days to 18yo (aka Bacterial meningitis score for infants >2mo and well appearing)
  • Positive CSF gram stain (61% sensitive; 99% specific)
  • CSF neutrophil count >1000cells/microlitre
  • CSF protein >80mg/dL
  • Peripheral blood neutrophils >10
  • History of seizure before or at time of presentation
• Negative score does not rule out herpesvirus or Lyme disease
• For those with CSF pleocytosis and likelihood of viral meningitis, even with negative bacterial meningitis score, can discharge after stat dose of ceftriaxone and ensure follow-up in 24 hours (Tintinalli)

• Best to admit those <2mo with any pleocytosis, all children who appear ill and administer antibiotics in ED
• Infants with aseptic meningitis should be admitted as at risk of dehydration and subsequent neurological and learning difficulties
• Children with cochlear implants have 30x the risk of S. pneumoniae meningitis
• Papilloedema
  • Uncommon in uncomplicated meningitis and suggests as more chronic process such as intracranial abscess, subdural empyema or occlusion of a dural venous sinus
• 10-20% of children with bacterial meningitis have focal neurological signs
• Seizures (focal or generalised) occur in 20-30% of children with meningitis

Which ones get an LP?

• All infants <1 month
• Any infant 1-3 months old who does not appear well with no other source identifiable
• Any infant >3 months with is very unwell or in whom clinical signs exist

Who gets dexamethasone and antibiotics immediately and delayed LP?

• Coma
• Signs of raised ICP
• Cardiovascular compromise
• Respiratory compromise
• Focal neurological signs or seizures
• Recent seizures within 30 minutes or not regained normal consciousness
• Coagulopathy/thrombocytopaenia
• Local infection
• Febrile child with purpura in whom meningococcal is suspected

Who gets a CT prior to LP?

• Focal neurological signs only
• Does not rule out raised ICP
• Don’t delay antibiotics waiting for this

Complications of LP

• Failure to obtain specimen
• Traumatic tap
• Bleeding
• Post-LP headache (5-15%)
• Transient paraesthesia/numbness (very uncommon)
• Respiratory arrest from positioning (rare)
• Spinal haematoma/abscess (rare)
• Tonsillar herniation (extremely rare in absence of CI)

Analgesia/anaesthesia

• Non-pharmacological techniques
• EMLA if not urgent (not in this case)
• Up to 0.4mL/kg of 1% lignocaine SC (4mg/kg)
• Oral sucrose if <3mo
• Sedation, including NO, if >6mo and normal conscious state

Procedure

• Monitor pulse oximetry +- ECG
• 22G or 25G bevelled spinal needles with stylet (reduces risk of spinal epidermoid tumours)
  • 25G pencil point with introducer in older children (reduces risk of post-procedural headache in adults)
• Iliac crests = L3/4
  • Conus medularis ends at L3
  • Aim for L3/4 or L4/5 interspinous space
• Bevel to side if sitting up or to ceiling if lying on side
• Aim for umbilicus
• 5-10 drops into 2 numbered sterile tubes
• Replace stylet and withdraw needle and stylet

Empirical antibiotic guideline (LCH)

• <1mo
  • As below but see neonatal dosing guidelines 
  • Assume all have meningitis
  • Cefotaxime 50mg/kg + Ampicillin 50mg/kg q6h

• 1-2mo
  • Ampicillin 50mg/kg IV q6h + Gentamicin 7.5mg/kg IV once daily (max 320mg if <10 years old)
  • If meningitis suspected:
    • Cefotaxime 50mg/kg IV q6h + Ampicillin 50mg/kg IV q6h
    • + Aciclovir 20mg/kg q8h if encephalitis suspected
  • If nmMRSA suspected (boils, previous nmMRSA)
    • Add Lincomycin 15mg/kg q8h
  • If septic shock requiring inotropes:
    • Add Vancomycin 15mg/kg q6h

• >2mo
  • Cefotaxime 50mg/kg IV q6h
  • If meningitis suspected: Cefotaxime 50mg/kg q6h
    • If gram-positive cocci in CSF add Vancomycin 15mg/kg q6h
    • If more than 3mo: Dexamethasone 0.15mg/kg q6h for 4 days if able to start prior to or within 1 hour of antibiotics
    • If encephalitis suspected: Aciclovir 500mg/m2/dose q8h
  • If nmMRSA suspected (boils, previous nmMRSA)
    • Add lincomycin 15mg/kg q8h
  • If septic shock requriing inotropes
    • Add vancomycin 15mg/kg q6h + Gentamicin 7.5mg/kg OD

Positive blood cultures in >3mo

• Recall all children with positive BC
• If S. pneumoniae
  • If receiving appropriate antibiotics, is clinically well and afebrile: Complete course of therapy
  • If afebrile, clinically well but not receiving antibiotics: Neither further Ix or antibiotics appear to be necessary unless specific focus of infection identified
  • If febrile: complete sepsis evaluation
• If N. meningitidis: Admit for parental antibiotics
• If MRSA: Admit for parenteral antibiotics
• If other organisms: Often more conservative course is appropriate

What if the child is unvaccinated?

• Up to 3 years old, guidelines recommend treating as per pre-vaccination era
• All get FBC and BC
• If WCC >15, should get CXR, admission and empirical antibiotics to cover S. pneumoniae and Hib invasive infection (Ceftriaxone or Augmentin are reasonable)**
• LP if suspected meningitis

The old SIRS rules

• 2 of four (one must be temperature or leukocyte count)
  • Core temp >38.5 or <36
  • Tachycardia
    • Mean heart rate >2SD above normal for age in absence of other cause
    • If <1yo: Bradycardia <10^th centile for age in absence of other cause
  • Mean RR >2SD above normal for age
  • Leukocyte count elevated or depressed for age or >10% immature neurophils

Leukocyte count for age

• Age 12 hours old: 13.0 to 38.0
• Age 2 weeks old: 5.0 to 20.0
• Age 6 Months to 2 years: 6.0 to 17.5 (Mean 11.0)
• Age 4 Years: 5.5 to 15.5 (Mean 9.1)
• Age 6 Years: 5.0 to 14.5 (Mean 8.5)
• Age 8 to 16 Years: 4.5 to 13.5 (Mean 8.1)
• Age over 21 Years: 4.5 to 11.0 (Mean 7.4)

Congenital HSV

• Suspect in full-term infants <4 weeks and premature infants (<32 weeks gestation) < 8 weeks old with any of the following:
  • Hx of HSV in mother in third trimester
  • Skin lesions on infant
  • Ill-appearing
  • Seizure with current illness
  • ALT or AST >100
  • CSF pleocytosis
• 60-80% of babies with HSV have no known exposure so must maintain high index of suspicion
• Start acyclovir 60mg/kg/day for all suspected cases

GBS

• Early-onset (<7 days)
  • Sepsis, pneumonia, meningitis
  • Prevented by intrapartum antibiotics for GBS-positive women and prolonged ROM
• Late onset (7 days to 3 months)
  • Same but meningitis more common
  • Not prevented by intrapartum antibiotics

Temperature measurement

• Rectal is most accurate
  • CI: Immunosuppression
• Tympanic best for older children
  • Some evidence of inaccuracy in infants <3mo due to different anatomy
  • Differs by 0.3 degrees with sensitivity to detect fever from 51-97%
• Axillary in infants/neonates
• Electronic, infrared equally accurate
• Axillary underestimates core temp by 0.5 degrees
  • In neonates, axillary appears more accurate with difference of 0.5 and sensitivity of 98%

Petechiae

• Hospitalised chidlren with Fever + petechiae = 7-11% rate of meningococcal
• Most common cause of petechiae is mechanical e.g. wretching
  • Usually above nipple line vs. SBI anywhere
• Empirical ceftriaxone or cefotaxime must be considered and most children should get WCC, BC, platelet count and coagulation studies

AAP Guideline on Management of Well-Appearing infants 8-60 days old

• Emphasises balance to be reached regarding risks of overtreatment/iatrogenesis vs. missed/undertreated invasive bacterial infection
• Listeria monocytogenes has become far less common in light of improved food safety in the US at least
• Increasing utility of inflammatory markers including derived WCC values (vs. population norms), absolute neutrophil counts, CRP and Procalcitonin in light of emerging evidence
• Emerging technologies capable of diagnosing viral infections rapidly may play a role in limiting antibacterial therapy and hospitalisation in certain populations
• Enterovirus PCR testing should be performed on pleocytic CSF and during months with seasonal increase in enterovirus incidence
• If CSF PCR is positive for Enterovirus, antibiotics can usually be discontinued as dual infection with bacteria and Enterovirus is rare
• While this guideline is for use in infants with a documented rectal temperature >38.0, studies have shown a documented temperature >38.5 carries an increased risk of invasive bacterial infection
• Algorithms
  • 8-21 days old, well-appearing, with no evident source of infection and temp >38.0
    • Urinalysis, BC and LP
    • Empiric parenteral antimicrobials
    • May obtain inflammatory markers to guide further therapy (such as discontinuing antibiotics)
    • If at risk of HSV -> Send HSV studies and start empiric acyclovir
  • 22 to 28 days old
    • Urinalysis, BC and inflammatory markers
    • If abnormal inflammatory markers (procalcitonin >0.5 or
      Absolute neutrophil count >5200/mm3 OR >38.5 degrees or CRP >20 or absolute neutrophil count >4000/mm3) -> Perform LP
      • If CSF not obtained, pleocytosis (raised WCC >5) or uninterpretable -> Administer parenteral antibiotics and admit
      • If CSF normal, can administer parenteral antibiotics and observe at home and review within 24 hours or admit to hospital and consider parenteral antibiotics
    • If normal inflammatory markers can consider LP
      • If CSF pleocytosis or traumatic -> Administer parenteral antibiotics and admit
      • If CSF normal -> Can administer parenteral antibiotics and send home for review in 24 hours or observe in hospital and consider antibiotics
      • If CSF not obtained -> Can administer parenteral antibiotics and observe in hospital
  • 29 to 60 days old
    • Urinalysis, BC and inflammatory markers
    • If abnormal inflammmatory markers -> Can perform LP
      • If CSF pleocytosis -> Administer parenteral antibiotics and admit
      • If CSF normal -> May administer oral or parenteral antibiotics and observe in hospital or at home
      • If CSF not obtained or uninterpretable -> Can administer parenteral antibiotics and observe in hospital or at home
    • If normal inflammatory markers and positive urine -> Can avoid LP and administer oral antibiotics with close observation at home
    • If normal inflammatory markers and negative urine -> Can avoid LP and observe closely at home

Last Updated on September 21, 2022 by Andrew Crofton