What is the treatment for febrile neutropenia?

Management of Febrile Neutropenia

Immediate empiric antibiotic therapy is essential for febrile neutropenia, with high-risk patients requiring intravenous monotherapy with an anti-pseudomonal beta-lactam (cefepime, piperacillin-tazobactam, or meropenem) and low-risk patients potentially receiving oral antibiotics. 1

Risk Stratification

First, stratify patients using the Multinational Association for Supportive Care in Cancer (MASCC) scoring index:

Characteristic	Score
Burden of illness: no or mild symptoms	5
Burden of illness: moderate symptoms	3
Burden of illness: severe symptoms	0
No hypotension (systolic BP >90 mmHg)	5
No chronic obstructive pulmonary disease	4
Solid tumor/lymphoma with no previous fungal infection	4
No dehydration	3
Outpatient status (at onset of fever)	3
Age <60 years	2

• Score ≥21: Low-risk (6% complication rate, 1% mortality)
• Score <21: High-risk 1

Initial Antibiotic Therapy

High-Risk Patients

• First-line treatment: Monotherapy with anti-pseudomonal beta-lactam:

  • Cefepime 2g IV every 8 hours 2
  • Piperacillin-tazobactam
  • Meropenem 1

• Do not routinely add aminoglycosides to initial therapy as they increase nephrotoxicity without improving outcomes 3

• Vancomycin is not recommended for routine initial therapy unless specific indications exist:

  • Suspected catheter-related infection
  • Known colonization with MRSA
  • Hemodynamic instability
  • Skin/soft tissue infection 4

Low-Risk Patients

• Can receive oral antibiotics (quinolone plus amoxicillin-clavulanate)
• Do not use quinolone if patient was on quinolone prophylaxis 1
• Consider outpatient management if:
  • No focus of bacterial infection
  • No signs of systemic infection besides fever
  • Reliable patient with 24/7 access to medical care
  • Evidence of marrow recovery 4, 5

Monitoring and Reassessment at 48-72 Hours

If Patient Becomes Afebrile with ANC ≥0.5×10⁹/L

• Low-risk with no cause found: Consider changing to oral antibiotics 4
• High-risk with no cause found: If on dual therapy, aminoglycoside may be discontinued 4
• When cause found: Continue appropriate specific therapy 4

If Still Febrile at 48-72 Hours

• If clinically stable: Continue initial antibacterial therapy
• If clinically unstable: Broaden antibiotic coverage
  • Consider adding a glycopeptide (vancomycin)
  • Consider changing to carbapenem plus glycopeptide
  • Seek infectious disease consultation 4

Antifungal Therapy

• Not indicated initially
• Consider if fever persists >96 hours (4-6 days) despite appropriate antibacterial therapy 4, 1
• Options include:
  • Voriconazole or liposomal amphotericin B for suspected aspergillosis
  • Fluconazole for low risk of aspergillosis and no prior azole exposure
  • Echinocandin (caspofungin) or liposomal amphotericin B if prior azole exposure or colonization with non-albicans Candida 4, 1

Duration of Therapy

• If ANC ≥0.5×10⁹/L, patient asymptomatic, afebrile for 48h, and negative blood cultures: Discontinue antibiotics 4
• If ANC remains <0.5×10⁹/L but patient has been afebrile for 5-7 days without complications: Antibiotics can be discontinued 4
• Exception: High-risk cases with acute leukemia or after high-dose chemotherapy may continue antibiotics for up to 10 days or until neutrophil recovery 4

Role of G-CSF

• Consider G-CSF (filgrastim) in older patients after completing chemotherapy 1
• Prophylactic G-CSF is recommended when anticipated risk of fever and neutropenia is >20% 1
• G-CSF has been shown to reduce the incidence of febrile neutropenia (40% vs 76% in placebo) in patients receiving myelosuppressive chemotherapy 6

Infection Prevention Measures

• Hand hygiene is crucial
• Skin and oral care are essential
• Avoid rectal procedures
• Dietary restrictions:
  • Consume only bottled or boiled water
  • Well-cooked foods only
  • Avoid raw vegetables, fruits, meats, and unpasteurized dairy 1

Common Pitfalls to Avoid

1. Delaying antibiotic initiation - Start empiric therapy immediately after obtaining cultures
2. Overuse of vancomycin - Reserve for specific indications
3. Adding aminoglycosides routinely - Increases toxicity without clear benefit
4. Premature discontinuation of antibiotics - Follow guidelines for duration based on neutrophil recovery
5. Failure to reassess - Daily evaluation is essential to modify therapy as needed
6. Delayed antifungal therapy - Consider after 4-6 days of persistent fever

Remember that febrile neutropenia is associated with significant mortality (11-36%) and requires prompt, appropriate management to improve outcomes 1.