What is the recommended treatment for neutropenic fever?

Treatment of Neutropenic Fever

For patients with neutropenic fever, the recommended first-line treatment is an anti-pseudomonal β-lactam agent such as cefepime (2g IV every 8 hours) as monotherapy. 1

Initial Assessment and Management

• Definition of neutropenia: Absolute neutrophil count (ANC) < 1500 cells/mm³

  • Mild: 1000-1500 cells/mm³
  • Moderate: 500-1000 cells/mm³
  • Severe: < 500 cells/mm³ 1

• Definition of fever: Temperature > 100°F (37.8°C) or increase of 2°F (1.1°C) over baseline 1

• Risk stratification: Use the Multinational Association for Supportive Care in Cancer (MASCC) risk index to categorize patients as:

  • Low-risk: score ≥ 21
  • High-risk: score < 21 1

Empiric Antibiotic Therapy

First-line Treatment:

• Anti-pseudomonal β-lactam monotherapy such as cefepime 2g IV every 8 hours 1, 2
  • Cefepime has demonstrated efficacy in clinical trials with response rates of 61% in evaluable episodes 3
  • FDA approved for empiric treatment of febrile neutropenic patients 2

For Persistent Fever:

• If fever persists after 72 hours of initial therapy, add:

  • Vancomycin or teicoplanin for gram-positive coverage 4

• If fever persists > 96 hours, consider adding:

  • Empiric antifungal therapy with caspofungin or liposomal amphotericin B 1

Special Considerations

High-Risk Patients:

• For patients with high risk for severe infection (history of bone marrow transplantation, hypotension, underlying hematologic malignancy, or severe/prolonged neutropenia):
  • Combination therapy may be more appropriate than monotherapy 2
  • Consider adding an aminoglycoside such as amikacin to the β-lactam regimen 5

Duration of Therapy:

• Continue antibiotics until neutrophil recovery (ANC ≥ 500/mm³) 6, 1
• For patients whose fever resolves but remain neutropenic, reevaluate the need for continued antimicrobial therapy frequently 2

Prophylactic Measures

• Antibacterial prophylaxis: Fluoroquinolone with streptococcal coverage or fluoroquinolone plus penicillin 6

  • Levofloxacin or ciprofloxacin 500 mg orally daily from onset of neutropenia until ANC > 500/mm³ 1

• Antiviral prophylaxis: Acyclovir or congeners 6

  • Acyclovir 400 mg or valacyclovir 500 mg orally twice daily 1

• Antifungal prophylaxis: Fluconazole 6

  • Fluconazole 400 mg orally daily until ANC > 1000/mm³ 1

Monitoring and Follow-up

• Daily assessment of fever trends and clinical status
• Monitor complete blood count every 2-3 days
• Continue close monitoring until resolution of symptoms and recovery of neutrophil count 1
• Consider G-CSF (filgrastim) if neutropenia is severe and prolonged, especially with signs of clinical deterioration 1

Common Pitfalls to Avoid

1. Delaying antibiotic administration: Prompt empiric antibiotic therapy is critical for neutropenic fever patients 5

2. Inappropriate monotherapy in high-risk patients: Insufficient data support cefepime monotherapy in patients with history of bone marrow transplantation, hypotension, underlying hematologic malignancy, or severe/prolonged neutropenia 2

3. Failure to reassess: Patients with persistent fever require reevaluation and potential modification of the antibiotic regimen 1

4. Overlooking fungal infections: Consider antifungal therapy if fever persists beyond 96 hours 1