What is the treatment for febrile neutropenia?

Treatment of Febrile Neutropenia

Immediate empiric broad-spectrum antibiotic therapy should be initiated within 1 hour of presentation in patients with febrile neutropenia to reduce mortality. 1

Initial Assessment and Risk Stratification

Risk assessment is crucial for determining appropriate management:

High-risk features:

• Profound neutropenia (ANC <100 cells/mm³) expected to last >7 days
• MASCC score <21
• Hemodynamic instability
• Oral/GI mucositis
• New pulmonary infiltrates
• History of recent bone marrow transplantation
• Underlying hematologic malignancy
• Severe or prolonged neutropenia 2, 1

Low-risk features:

• Brief expected neutropenia (<7 days)
• MASCC score ≥21
• Few comorbidities 1

Initial Antibiotic Therapy

First-line empiric therapy:

• Monotherapy with an antipseudomonal β-lactam such as:
  • Meropenem
  • Imipenem/cilastatin
  • Piperacillin/tazobactam
  • Cefepime (2g IV every 8 hours) 2, 1, 3

Add vancomycin if:

• Suspected catheter-related infection
• Known MRSA colonization
• Severe sepsis or septic shock
• Pneumonia with severe hypoxia or extensive infiltrates
• Skin/soft tissue infection 1

Add aminoglycoside if:

• Severe sepsis
• Suspected Pseudomonas infection
• Local high resistance patterns 1

Management Based on Response at 48 Hours

If apyrexial and ANC ≥0.5 × 10⁹/L at 48h:

• Low-risk and no cause found: Consider changing to oral antibiotics
• High-risk and no cause found: If on dual therapy, aminoglycoside may be discontinued
• When cause found: Continue appropriate specific therapy 2

If still pyrexial at 48h:

• If clinically stable: Continue initial antibacterial therapy
• If clinically unstable: Broaden antibiotic coverage or rotate antibiotics
• Consider consulting infectious disease specialist or clinical microbiologist 2

Antifungal Therapy

When pyrexia lasts >4-6 days, consider initiating antifungal therapy:

• For presumed aspergillosis: Voriconazole or liposomal amphotericin B
• For patients at risk of invasive candidiasis: Echinocandin (first-line) or fluconazole 2, 1

Special Situations

Suspected meningitis or encephalitis:

• Lumbar puncture is mandatory
• For bacterial meningitis: Ceftazidime plus ampicillin (to cover Listeria) or meropenem
• For viral encephalitis: High-dose acyclovir 2

Suspected viral infection:

• Acyclovir for suspected herpes virus infections
• Ganciclovir only when high suspicion of CMV infection 2

Duration of Therapy

• If ANC ≥0.5 × 10⁹/L, patient asymptomatic, afebrile for 48h, and negative blood cultures: Discontinue antibiotics
• If ANC <0.5 × 10⁹/L, no complications, afebrile for 5-7 days: Discontinue antibiotics
• Exception: High-risk cases with acute leukemia or after high-dose chemotherapy - continue antibiotics for up to 10 days or until ANC ≥0.5 × 10⁹/L 2
• For documented infections: Continue antibiotics for at least the duration of neutropenia or 10-14 days, whichever is longer 1

Outpatient Management Considerations

Low-risk patients may be treated as outpatients if they meet specific criteria:

• No signs of systemic infection
• Ability to take oral medications
• Reliable caregiver support and transportation
• Access to emergency care 1, 4

Common Pitfalls to Avoid

1. Delaying antibiotic administration - mortality increases by 7.6% for every hour of delay 1
2. Inadequate initial coverage - ensure broad-spectrum coverage against both gram-positive and gram-negative organisms
3. Failure to reassess - daily evaluation of fever trends, bone marrow and renal function is essential 2
4. Premature discontinuation of antibiotics - follow guidelines for duration based on neutrophil recovery
5. Missing fungal infections - consider antifungal therapy for persistent fever despite appropriate antibacterial coverage

Cefepime has shown good efficacy as monotherapy for febrile neutropenia, with response rates of 61-83% in clinical studies 5, 6, but appropriate modifications should be made based on clinical response and culture results.