Fever Without Apparent Source in Infants and Young Children

Background

• Fever without apparent source describes an acute febrile illness with no obvious source of fever after thorough history and physical exam.
• Fever is generally defined as a rectal temperature ≥ 38 degrees C (100.4 degrees F).
• Fever without apparent source is usually caused by a self-limiting viral infection and/or urinary tract infection but may be the first sign of bacteremia or bacterial meningitis.
• The most important goal is to identify an invasive bacterial infection, if present.
• Fever in infants < 60 days old requires special consideration.
• Management of febrile, ill-appearing infants and children, especially those with concerning vital signs, includes resuscitation, sepsis evaluation, and antibiotics started within 1 hour as detailed in Late-onset Neonatal Sepsis and Sepsis Treatment in Children.

Evaluation and Management

Infants Aged 8-21 Days

• In well-appearing infants, clinical and laboratory features help identify the cause of the fever and assess the risk for urinary tract infection, bacteremia, and bacterial meningitis.
• Obtain a catheterized or suprapubic aspiration urinalysis (and culture if urinalysis positive) and a blood culture (Strong recommendation).
• Consider obtaining inflammatory markers such as procalcitonin, C-reactive protein, and absolute neutrophil count (ANC) (Weak recommendation).
• Perform a lumbar puncture and cerebrospinal fluid analysis (CSF) (Strong recommendation).
• Assess the risk of herpes simplex virus with maternal history and infant physical examination.
• Begin parental antimicrobial therapy (Strong recommendation), and acyclovir, if infection with herpes simplex virus is a concern.
• Follow recommended empirical antibacterial therapy.
• Consider monitoring in the hospital while awaiting results of bacterial cultures (Weak recommendation).
• Once test results are available, and a pathogen or source is not identified, discontinue parenteral antimicrobial agents and discharge home if (Strong recommendation)
  • negative culture for 24-36 hours or only positive for contaminants
  • infant continues to appear clinically well or is improving
  • no other reasons for hospitalization
• If positive for bacterial pathogen in urine, blood or CSF, treat with targeted antimicrobial therapy (Strong recommendation).

Infants Aged 22-28 Days

• Clinical and laboratory features help identify the cause of the fever and assess the risk for urinary tract infection, bacteremia, and bacterial meningitis.
• Obtain a urinalysis and (Strong recommendation)
  • if urinalysis is positive from sample collected by catheterization or suprapubic aspiration of bladder, obtain culture
  • if urinalysis is positive from sample collected by bag, spontaneous void, or stimulated void, obtain culture from sample collected by catheterization or suprapubic aspiration of bladder
• Obtain a blood culture (Strong recommendation).
• Assess inflammatory markers, specifically, procalcitonin (if available) with either absolute neutrophil count (ANC) or C-reactive protein (CRP) (Strong recommendation).
• If procalcitonin is not available, use temperature > 38.5 degrees C (101.3 degrees F) as marker of inflammation plus ANC and CRP (Strong recommendation).
• Consider performing a lumbar puncture for CSF analysis even if no inflammatory markers are abnormal, urinalysis is normal, and blood and urine cultures are pending (Weak recommendation).
• Begin antimicrobial therapy in the hospital setting if CSF analysis suggests bacterial meningitis or urinalysis is positive (Strong recommendation).
• Follow recommended empirical antibacterial therapy.
• If positive for bacterial pathogen in urine, blood or CSF, treat with targeted antimicrobial therapy (Strong recommendation).
• Consider managing infants at home who have: (Weak recommendation)
  • normal urinalysis
  • normal inflammatory markers
  • normal CSF analysis or enterovirus-positive
  • verbal teaching and written instructions provided to caregiver
  • follow-up plans in place

Infants Aged 29-60 Days

• Clinical and laboratory features help identify the cause of the fever and assess the risk for urinary tract infection, bacteremia, and bacterial meningitis.
• Obtain a urinalysis and (Strong recommendation)
  • collect sample by bag, spontaneous void, or stimulated void and if positive, obtain catheterization or suprapubic aspiration (SPA) sample for culture
  • alternatively, obtain catheterization or SPA sample for urinalysis followed by culture if urinalysis is positive
  • circumcised boys are exempt from this recommendation due to low likelihood of urinary tract infection (< 1%)
• Obtain a blood culture (Strong recommendation).
• Consider assessing inflammatory markers such as procalcitonin (if available) with either absolute neutrophil count (ANC) or C-reactive protein (CRP) (Weak recommendation).
• If procalcitonin is not available, consider temperature > 38.5 degrees C (101.3 degrees F) as marker of inflammation plus ANC and CRP (Weak recommendation).
• Consider performing a lumbar puncture for CSF analysis only if inflammatory markers are abnormal (Weak recommendation).
• Begin antimicrobial therapy in the hospital setting if CSF analysis suggests bacterial meningitis or urinalysis is positive (Strong recommendation).
• Consider parenteral antimicrobial therapy use in infants with both (Weak recommendation):
  • normal CSF analysis if CSF obtained
  • any abnormal IM among those obtained
• Start oral antimicrobial therapy if all of following are met (Strong recommendation):
  • normal CSF analysis if CSF obtained
  • positive urinalysis
  • no IM obtained is abnormal
• Follow recommended empirical antibacterial therapy.
• If positive for bacterial pathogen in urine, blood or CSF, treat with targeted antimicrobial therapy (Strong recommendation).
• Infants may be managed at home if all of the following are met (Weak recommendation):
  • normal CSF analysis if obtained
  • negative urinalysis
  • all IMs obtained are normal
  • appropriate caregiver education has been provided
  • follow-up plans in place for reevaluation in 24 hours
  • plans in place in event of change in clinical status, with means of communication between family and providers and access to emergency medical care

Infants and Young Children > 60 Days Old

• In fully vaccinated infants and young children > 60 days old, clinical and laboratory features help identify the cause of the fever and to assess the risk for serious bacterial infection (SBI).
• If high risk for serious illness, obtain complete blood count, blood culture, CRP, urine testing, and consider lumbar puncture, chest x-ray, serum electrolytes, and blood gas based on clinical evaluation.
• If intermediate risk for serious illness, obtain complete blood count, blood culture, CRP, urine testing, chest x-ray for fever > 39 degrees C (102.2 degrees F) and WBC > 20 × 10⁹/L and consider lumbar puncture in infants < 1 year old
• If low risk for serious illness, obtain urine testing and assess for symptoms and signs of pneumonia.
• Consider empiric antibiotics for all children with suspected SBI.