What is the treatment for febrile neutropenia?

Management of Febrile Neutropenia

Initial empiric treatment of febrile neutropenia should be monotherapy with an anti-pseudomonal β-lactam, such as cefepime 2g IV every 8 hours, meropenem, imipenem-cilastatin, or piperacillin-tazobactam. 1

Initial Assessment and Risk Stratification

• Determine patient's risk category:

  • Low-risk: MASCC score ≥21, clinically stable, no signs of systemic infection 1
  • High-risk: MASCC score <21, profound neutropenia (ANC <100 cells/mm³) expected to last >7 days, hemodynamic instability, oral/GI mucositis, new pulmonary infiltrates, history of recent bone marrow transplantation, underlying hematologic malignancy 1

• Required diagnostic evaluation:

  • Complete blood count with differential to confirm neutropenia (ANC <500/mcL)
  • Blood cultures (at least two sets, including from central venous catheter if present)
  • Additional cultures based on symptoms (urine, sputum, stool)
  • Chest radiograph and additional imaging based on symptoms 1

Antibiotic Therapy

First-line Treatment

• For high-risk patients: Intravenous monotherapy with:

  • Cefepime 2g IV every 8 hours 1, 2
  • Alternative options: meropenem, imipenem-cilastatin, or piperacillin-tazobactam 1

• For low-risk patients:

  • Consider oral therapy for clinically stable patients (ciprofloxacin plus amoxicillin-clavulanate) 1
  • Avoid fluoroquinolones if patient was on fluoroquinolone prophylaxis 1

Additional Antibiotics

• Vancomycin should only be added for specific indications:
  • Suspected catheter-related infection
  • Known MRSA colonization
  • Skin/soft tissue infection
  • Pneumonia with hypoxia
  • Hemodynamic instability 1

Assessment of Response and Subsequent Management

At 48 Hours:

• If patient is apyrexial and ANC ≥0.5×10^9/L:

  • Low-risk: Consider changing to oral antibiotics 3
  • High-risk: If on dual therapy, aminoglycoside may be discontinued 3

• If still febrile at 48 hours:

  • If clinically stable: Continue initial antibacterial therapy
  • If clinically unstable: Broaden antibiotic coverage or rotate antibiotics 3
  • Consider adding aminoglycoside if deterioration occurs on monotherapy 1

Antifungal Therapy

• Add empiric antifungal therapy if fever persists after 3-5 days of antibacterial therapy 1
• Options include liposomal amphotericin B, caspofungin, or voriconazole 1
• When pyrexia lasts >4-6 days, initiation of antifungal therapy may be needed 3

Duration of Therapy

• If neutrophil count ≥0.5×10^9/L, patient is asymptomatic, has been afebrile for 48 hours, and blood cultures are negative: discontinue antibiotics 3

• If neutrophil count ≤0.5×10^9/L, patient has no complications and has been afebrile for 5-7 days: antibiotics can be discontinued 3

• Exception: In high-risk cases with acute leukemia and following high-dose chemotherapy, antibiotics are often continued for up to 10 days or until neutrophil count ≥0.5×10^9/L 3

• For documented infections: continue therapy for at least 7-14 days 1

Special Considerations

• Catheter-related infections may require catheter removal for certain pathogens 1
• Viral infections (HSV or VZV) require adding acyclovir 1
• Growth factor support (G-CSF) is indicated for patients with high-risk neutropenia following chemotherapy 1

Common Pitfalls to Avoid

• Delaying antibiotic administration (should be given within 2 hours of presentation)
• Inappropriate use of vancomycin as initial therapy without specific indications
• Premature discontinuation of antibiotics before neutropenia resolves
• Changing antibiotics for persistent fever alone when patient is clinically stable
• Failure to consider antifungal therapy when fever persists 1

The efficacy of cefepime monotherapy has been demonstrated in multiple studies, with success rates of 83.3% to 91.7% 4, 5. In patients with prolonged neutropenia, however, there may be higher risk of treatment failure, requiring appropriate therapeutic modifications 5.