What is the treatment for febrile neutropenia?

Treatment of Febrile Neutropenia

First-line therapy for febrile neutropenia should be immediate administration of intravenous empirical antibiotic therapy with an anti-pseudomonal β-lactam agent such as cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam within 2 hours of presentation. 1

Initial Assessment and Risk Stratification

1. Laboratory Workup:

   • Complete blood count with differential
   • Blood chemistry profile (creatinine, BUN, electrolytes, liver enzymes, bilirubin)
   • Blood cultures (at least two sets, including from central venous catheter if present)
   • Additional cultures from suspected infection sites
   • Chest radiography for patients with respiratory symptoms 1

2. Risk Assessment:

   • Use the Multinational Association for Supportive Care in Cancer (MASCC) score:
     • Score ≥21: Low risk
     • Score <21: High risk 1
   • High-risk features include:
     • Profound neutropenia (ANC <100 cells/mm³) expected to last >7 days
     • Hemodynamic instability
     • Oral/GI mucositis interfering with swallowing or causing severe diarrhea
     • Neurologic or mental status changes
     • Catheter-related infection
     • New pulmonary infiltrate or hypoxemia
     • Hepatic or renal insufficiency 1

Treatment Algorithm

1. High-Risk Patients

• Antibiotic Therapy:

  • Monotherapy with an anti-pseudomonal β-lactam:
    • Cefepime: 2g IV every 8 hours 1, 2
    • Meropenem: 1g IV every 8 hours
    • Imipenem-cilastatin: 500mg IV every 6 hours
    • Piperacillin-tazobactam: 4.5g IV every 6-8 hours 1

• Add Vancomycin ONLY for specific indications:

  • Suspected catheter-related infection
  • Known MRSA colonization
  • Skin/soft tissue infection
  • Pneumonia with hypoxia
  • Hemodynamic instability 1

• Add Antifungal Therapy:

  • If fever persists after 3-5 days of antibacterial therapy:
    • Options include liposomal amphotericin B, caspofungin, or voriconazole 1
  • Antifungal prophylaxis with fluconazole 400 mg daily until ANC >1000/mm³ 1

2. Low-Risk Patients

• Oral Therapy Option:
  • Clinically stable patients may receive:
    • Ciprofloxacin plus amoxicillin-clavulanate
    • Avoid fluoroquinolones if patient was on fluoroquinolone prophylaxis 1

Duration of Therapy

• Continue antibiotic therapy until neutrophil recovery (ANC >500/mm³) or for at least 7-14 days for documented infections 1
• For specific fungal infections like candidiasis and aspergillosis, longer treatment durations are required 1

Supportive Care

• Growth Factor Support:

  • Granulocyte colony-stimulating factor (G-CSF) is indicated for high-risk neutropenia
  • Reduces duration of neutropenia and risk of febrile neutropenia 1

• Infection Prevention:

  • Hand hygiene and infection control precautions
  • Private room with HEPA filtration if possible
  • Daily skin inspection and good oral hygiene
  • Avoid rectal thermometers, enemas, suppositories, and rectal examinations
  • Well-cooked foods; avoid prepared luncheon meats 1

Clinical Evidence Supporting Cefepime Monotherapy

Cefepime is FDA-approved for empiric treatment of febrile neutropenic patients 2. Clinical trials have demonstrated that cefepime monotherapy (2g IV every 8 hours) is effective in treating febrile neutropenia, with response rates of 61-83% without requiring additional antibiotics 3, 4.

Common Pitfalls to Avoid

1. Delaying antibiotic administration - Treatment should begin within 2 hours of presentation
2. Inappropriate use of vancomycin - Reserve for specific indications only
3. Premature discontinuation of antibiotics - Continue until neutrophil recovery or for at least 7-14 days
4. Changing antibiotics for persistent fever alone - Consider adding antifungals instead after 3-5 days
5. Failure to consider antifungal therapy when fever persists 1

Special Considerations

For patients at high risk for severe infection (recent bone marrow transplantation, hypotension, underlying hematologic malignancy, severe/prolonged neutropenia), antimicrobial monotherapy may not be appropriate, and combination therapy should be considered 2.