What is the treatment for Febrile Neutropenia (FN)

Treatment of Febrile Neutropenia (FN)

The treatment of febrile neutropenia requires immediate initiation of broad-spectrum antibiotics within one hour of presentation, with therapy selection based on risk stratification using the MASCC scoring system. 1

Risk Stratification

First, assess the patient's risk level using the MASCC (Multinational Association for Supportive Care in Cancer) 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

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

Initial Management

High-Risk Patients

1. Immediate hospital admission
2. Empiric antibiotic therapy:
   • Monotherapy with anti-pseudomonal beta-lactam (cefepime, piperacillin-tazobactam, or meropenem) 1, 2
   • Local bacterial resistance patterns should guide antibiotic selection 3
   • For patients with prolonged neutropenia or bacteremia, consider combination therapy with a beta-lactam plus aminoglycoside for synergistic effect 3

Low-Risk Patients

1. Initial inpatient management for at least 24 hours 3
2. Antibiotic options:
   • Intravenous monotherapy OR
   • Oral combination therapy: quinolone plus amoxicillin-clavulanate (do not use quinolone if patient was on quinolone prophylaxis) 3, 1
3. Early discharge can be considered after 24 hours if:
   • Clinically stable
   • Symptomatically improved
   • Evidence of fever resolution 3

Specific Clinical Scenarios

Central Venous Catheter-Related Infection

• Obtain blood cultures from both catheter and peripherally to measure differential time to positivity (DTTP) 3
• Add vancomycin through the line when infection is suspected 3, 1
• Teicoplanin is an alternative (can be used as line lock) 3
• Catheter removal indications:
  • Tunnel infections
  • Pocket infections (implanted ports)
  • Persistent bacteremia despite adequate treatment
  • Atypical mycobacterial infection
  • Candidemia 3
• For coagulase-negative Staphylococcus, catheter may be preserved if patient is stable 3

Cellulitis

• Add vancomycin to broaden coverage against skin pathogens 3

Candidosis/Fungal Infections

• Start with fluconazole if low risk for invasive aspergillosis and no prior azole exposure 3
• Switch to alternative antifungal if inadequate response 3
• For suspected invasive aspergillosis, use voriconazole or liposomal amphotericin B 3
• Consider empiric antifungal therapy if fever persists >96 hours despite appropriate antibacterial therapy 1

Pneumonia/Lung Infiltrates

• Perform CT scan and consider bronchoalveolar lavage if no prompt improvement 3
• Add a macrolide to beta-lactam antibiotic to cover atypical organisms 3
• Consider Pneumocystis jerovecii in patients with high respiratory rates or oxygen desaturation 3

Diarrhea

• Assess for Clostridium difficile and treat with metronidazole if suspected 3

Viral Infections

• For vesicular lesions or suspected viral infection, initiate acyclovir after appropriate samples are taken 3
• Reserve ganciclovir for suspected invasive cytomegalovirus infection 3

Meningitis/Encephalitis

• Perform lumbar puncture
• For bacterial meningitis: ceftazidime or meropenem plus ampicillin (to cover Listeria) 3
• For viral encephalitis: high-dose acyclovir 3

Monitoring and Follow-Up

Daily Assessment

• Clinical assessment (may require every 2-4 hours in severe cases)
• Monitor fever trends, complete blood counts, and renal function 3, 1
• Consider repeat imaging if clinically indicated 1

Response Evaluation at 48 Hours

• If afebrile 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 but clinically stable:
  • Continue initial antibacterial therapy 3
• If clinically unstable:
  • Broaden antibiotic coverage or rotate antibiotics 3
  • Consider adding a glycopeptide or changing to carbapenem plus glycopeptide 3
  • Seek advice from infectious disease specialist or clinical microbiologist 3

Antibiotic Discontinuation

• Can discontinue antibiotics if:
  • ANC ≥0.5×10^9/L
  • Afebrile for 48 hours
  • Negative cultures 1
• Consider discontinuing empirical antibiotics at 72 hours in low-risk patients who have been afebrile for at least 24 hours with negative blood cultures, regardless of marrow recovery status 1

Common Pitfalls and Caveats

1. Delayed antibiotic administration: Mortality increases with each hour of delay in administering antibiotics. Always initiate within 1 hour of presentation.

2. Inappropriate risk stratification: Incorrectly classifying a high-risk patient as low-risk can lead to inadequate treatment and poor outcomes.

3. Failure to consider local resistance patterns: Local epidemiological data should guide empiric antibiotic selection.

4. Premature antibiotic de-escalation: Do not discontinue antibiotics too early, especially in high-risk patients.

5. Overlooking fungal infections: Consider empiric antifungal therapy if fever persists beyond 96 hours of appropriate antibacterial therapy.

6. Inappropriate catheter management: Don't remove central lines without microbiological evidence of infection, but don't hesitate to remove when indicated.

7. Inadequate monitoring: Daily assessment of clinical status and laboratory parameters is essential for early detection of treatment failure or complications.