What is the approach to managing prolonged fever in pediatric patients?

Approach to Prolonged Fever in Pediatric Population

The management of prolonged fever in pediatric patients should follow a systematic risk-stratification approach, with empiric antibiotic therapy reserved for high-risk patients while focusing on identifying the underlying cause in all cases. 1

Definition and Initial Risk Assessment

• Prolonged fever definitions:

  • Fever without a source: present for 1 week without clear cause 2
  • Fever of unknown origin (FUO): daily fever for 8 days or more without apparent source 2

• Risk stratification is essential to guide management decisions:

  • High-risk patients: Those with cancer (especially AML, high-risk ALL, relapsed leukemia), undergoing hematopoietic stem cell transplantation (HSCT), prolonged neutropenia, or receiving high-dose corticosteroids 1
  • Low-risk patients: Otherwise healthy children without immunocompromise

Diagnostic Approach

For All Pediatric Patients with Prolonged Fever:

1. Blood cultures: Obtain from all lumens of central venous catheters if present, plus peripheral blood cultures 1
2. Urinalysis and urine culture: Consider in patients where clean-catch specimen is readily available 1
3. Chest radiography: Only in symptomatic patients 1
4. Complete blood count with differential: To assess for neutropenia and other abnormalities

For Immunocompromised/High-Risk Patients:

• Additional testing for invasive fungal disease (IFD) after 96 hours of persistent fever:
  • CT of lungs and targeted imaging of other clinically suspected areas of infection 1
  • Consider CT imaging of sinuses in children ≥2 years of age 1
  • Consider galactomannan in bronchoalveolar lavage and cerebrospinal fluid to support diagnosis of pulmonary or CNS aspergillosis 1
  • Do not use β-D-glucan testing for clinical decisions 1
  • Do not use fungal PCR testing in blood 1

Management Approach

General Principles:

• Primary goal: Identify and treat the underlying cause rather than just suppressing temperature 3
• Patient comfort: Ensure adequate fluid intake and consider antipyretics for symptomatic relief 3
• Preferred antipyretic: Paracetamol (acetaminophen) over NSAIDs, especially for viral infections 3

For Low-Risk Patients:

1. Observation with close follow-up may be appropriate if the child appears well
2. Antipyretics for comfort rather than temperature normalization 4
3. Consider discontinuation of empiric antibiotics at 72 hours if blood cultures are negative and the patient has been afebrile for at least 24 hours, even without marrow recovery, as long as careful follow-up is ensured 1
4. Consider outpatient management if infrastructure is in place to ensure careful monitoring and follow-up 1

For High-Risk/Immunocompromised Patients:

1. Initial empiric therapy:

   • Use monotherapy with antipseudomonal β-lactam or carbapenem 1
   • Reserve addition of second Gram-negative agent or glycopeptide for patients who are clinically unstable, when resistant infection is suspected, or for centers with high rate of resistant pathogens 1

2. Ongoing management (24-72 hours):

   • Do not modify initial empiric antibacterial regimen based solely on persistent fever in children who are clinically stable 1
   • Discontinue double coverage for Gram-negative infection or empiric glycopeptide after 24-72 hours if there is no specific microbiologic indication to continue combination therapy 1
   • If patient becomes clinically unstable with persistent fever: Escalate initial empiric antibacterial regimen to include coverage for resistant Gram-negative, Gram-positive, and anaerobic bacteria 1

3. Antifungal management (after 96 hours):

   • For persistent fever despite antibiotics: Initiate empiric antifungal treatment with either caspofungin or liposomal amphotericin B 1
   • Continue antibiotics until patient has negative blood cultures at 48 hours, has been afebrile for at least 24 hours, and has evidence of marrow recovery 1

Special Considerations

Neutropenic Fever:

• Immediate empiric antibiotics within 1 hour of presentation 3
• High-risk patients: Hospitalization with IV antibiotics
• Low-risk patients: Consider oral antibiotics or outpatient management if infrastructure supports careful monitoring 1

Persistent Fever:

• Stable patient: Persistent fever alone is not an indication to change antibiotics 3
• Unstable patient: Escalate antibiotic coverage and investigate for resistant organisms or non-bacterial causes

Common Pitfalls to Avoid

1. Focusing solely on temperature normalization rather than patient comfort and treating the underlying cause
2. Changing antibiotics based only on persistent fever in an otherwise stable patient
3. Failing to consider non-infectious causes of prolonged fever (drug fever, thromboembolism, malignancy)
4. Delaying empiric antibiotics in high-risk patients while awaiting culture results
5. Overuse of antipyretics when fever may be beneficial for host defense in some infections 3

By following this approach, clinicians can effectively manage pediatric patients with prolonged fever while minimizing unnecessary interventions and focusing on identifying and treating the underlying cause.