What is the management and workup for febrile neutropenia?

Management of Febrile Neutropenia: Workup and Treatment

Immediate broad-spectrum antibiotic therapy within 1 hour of fever onset is the cornerstone of febrile neutropenia management to reduce mortality and morbidity. 1

Initial Assessment and Workup

Immediate Clinical Evaluation

• Assess circulatory and respiratory function with vigorous resuscitation if needed
• Careful examination for potential infection foci (respiratory, gastrointestinal, skin, perineal/genitourinary, oropharynx, central nervous system)
• Note presence of indwelling IV catheters
• Check previous positive microbiology results 2

Essential Investigations Before Antibiotics

• Two sets of blood cultures (peripheral vein and any indwelling venous catheters)
• Urgent blood testing: complete blood count, renal and liver function, coagulation screen, C-reactive protein
• Urinalysis and culture
• Sputum culture if respiratory symptoms
• Stool culture if gastrointestinal symptoms
• Skin lesion sampling (aspirate/biopsy/swab) if present
• Chest radiograph 2

Risk Assessment

Use the MASCC (Multinational Association for Supportive Care in Cancer) scoring index to stratify patients:

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: Score ≥21 (6% complication rate, 1% mortality)
• High-risk: Score <21 2

Empiric Antibiotic Therapy

Initial Antibiotic Selection

• High-risk patients: Monotherapy with anti-pseudomonal beta-lactam (cefepime, piperacillin-tazobactam, or meropenem) 2, 1, 3

  • Consider combination therapy with aminoglycoside for patients with bacteremia or prolonged neutropenia 2

• Low-risk patients:

  • Inpatient oral antibiotics for stable patients (quinolone plus amoxicillin-clavulanate) 2
  • Do not use quinolone if patient was on quinolone prophylaxis 2

Special Considerations

• Add vancomycin for suspected catheter-related infection, known colonization with resistant gram-positive organisms, positive blood cultures for gram-positive bacteria, or hypotension 1
• Add metronidazole if clinical evidence of intra-abdominal or pelvic sepsis 2

Reassessment at 48 Hours

If Patient Becomes Afebrile and ANC ≥0.5×10^9/L:

• Low-risk with no cause found: Consider changing to oral antibiotics 2
• High-risk with no cause found: If on dual therapy, aminoglycoside may be discontinued 2
• When pathogen identified: Continue appropriate specific therapy 2

If Fever Persists at 48 Hours:

• If clinically stable: Continue initial antibacterial therapy 2
• If clinically unstable: Broaden antibacterial coverage to include resistant gram-negative, gram-positive, and anaerobic bacteria 2, 1
  • Options include adding a glycopeptide or changing to a carbapenem plus glycopeptide 2
  • Seek advice from infectious disease specialist or clinical microbiologist 2

Antifungal Therapy

• Initiate empirical antifungal therapy if fever persists >96 hours (3-7 days) despite appropriate antibacterial therapy 2, 1
• Before starting antifungal therapy, perform chest CT scan including liver and spleen 2

Antifungal Selection:

• If prior azole exposure or colonization with non-albicans Candida: Liposomal amphotericin B or echinocandin (caspofungin) 2, 1
• If low risk of aspergillosis and no prior azole prophylaxis: Fluconazole 2, 1
• For suspected aspergillosis: Voriconazole or liposomal amphotericin B 2
  • Consider adding echinocandin for unresponsive disease 2

Duration of Therapy

• Antibacterial therapy:

  • Discontinue if ANC ≥0.5×10^9/L, afebrile for 48 hours, and negative cultures 1
  • Consider discontinuation at 72 hours in low-risk patients with negative cultures who have been afebrile for 24 hours, regardless of marrow recovery 1

• Antifungal therapy:

  • Continue until neutropenia resolves
  • For documented fungal infection, continue for at least 14 days 2

Special Situations

Viral Infections

• If viral infection suspected, obtain appropriate samples and initiate aciclovir 2
• Use ganciclovir only when high suspicion of invasive cytomegalovirus infection 2

CNS Infections

• Perform lumbar puncture if CNS infection suspected
• For bacterial meningitis: Ceftazidime plus ampicillin (to cover Listeria) or meropenem 2
• For viral encephalitis: High-dose aciclovir 2

Common Pitfalls and Caveats

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

2. Overreliance on clinical signs: Signs and symptoms of infection may be minimal in neutropenic patients, especially those on corticosteroids. Maintain high suspicion even with minimal symptoms.

3. Inappropriate de-escalation: Do not modify initial antibiotic regimen based solely on persistent fever if the patient is clinically stable.

4. Overlooking fungal infections: Consider invasive fungal infections in patients with prolonged neutropenia and persistent fever despite antibacterial therapy.

5. Neglecting catheter-related infections: Central venous catheters are common sources of infection. Consider removal if catheter-related infection is suspected.

6. Inadequate monitoring: Daily assessment of fever trends, bone marrow and renal function is essential until fever resolves and neutrophil count recovers.