How should I manage a patient with leukopenia (white blood cell count 3,000/µL), mild neutropenia (absolute neutrophil count ~1,350/µL), negative C‑reactive protein, presenting with cough and fever?

Management of Febrile Neutropenia with Mild Neutropenia

Start empirical broad-spectrum antibiotics immediately (within 2 hours) with monotherapy using cefepime, ceftazidime, or a carbapenem (meropenem or imipenem-cilastatin), and do NOT add vancomycin unless specific criteria are met. 1

Risk Stratification

Your patient has:

• Absolute neutrophil count (ANC) of 1,350/µL (3,000 × 0.45 = 1,350)
• This is mild neutropenia (ANC 1,000-1,500/µL), not meeting the classic definition of severe neutropenia (ANC <500/µL) 1, 2
• However, fever with neutropenia <1,500/µL still requires urgent evaluation and treatment 3, 2

Critical point: The negative CRP is reassuring but does NOT exclude bacterial infection in neutropenic patients, as inflammatory responses may be blunted 4. However, CRP <30 mg/L maintained for 48 hours after fever onset has been associated with absence of documented infection in neutropenic patients 4.

Immediate Antibiotic Management

Choose monotherapy with ONE of the following: 1

• Cefepime (preferred for broad gram-negative and gram-positive coverage)
• Ceftazidime
• Meropenem or imipenem-cilastatin

Do NOT routinely add vancomycin unless the patient has: 1, 5

• Clinically apparent catheter-related infection
• Skin or soft tissue infection
• Hemodynamic instability
• Pneumonia on chest radiograph
• Blood cultures growing gram-positive bacteria before final identification
• Known colonization with MRSA or VRE

The IDSA explicitly states vancomycin shows no mortality benefit in empirical febrile neutropenia and increases risk of drug resistance and adverse effects, including drug-induced neutropenia itself. 5

Essential Diagnostic Workup

Obtain immediately: 1, 3

• At least 2 sets of blood cultures from different sites (peripheral vein and catheter if present)
• Complete blood count with differential
• Chest radiograph (given cough symptoms)
• Serum creatinine, BUN, transaminases
• Repeat CRP measurement (serial monitoring helpful)

Assessment at 48-72 Hours

If patient becomes afebrile by day 3: 1

• Continue same antibiotics if ANC remains <500/µL
• If ANC >500/µL for 2 consecutive days, cultures negative, and afebrile for 48 hours, stop antibiotics 1

If fever persists at 48-72 hours: 1

• If clinically stable: Continue same antibiotics (median time to defervescence is 5 days) 1
• If clinically deteriorating: Broaden coverage or rotate antibiotics; obtain infectious disease consultation 1
• If fever persists beyond 5-7 days: Consider empirical antifungal therapy (amphotericin B or alternative) 1

Risk Assessment for This Patient

This patient appears low-risk based on: 1

• ANC 1,350/µL (not profoundly neutropenic)
• No mention of hemodynamic instability
• No apparent complicated infection site

However, do NOT treat as outpatient initially given active fever and respiratory symptoms requiring evaluation 2, 6.

Common Pitfalls to Avoid

Do not add vancomycin empirically "just in case" - this increases drug resistance, toxicity risk, and can paradoxically cause drug-induced neutropenia 5. If vancomycin was started empirically without clear indication, discontinue by day 2-3 if cultures remain negative 5.

Do not wait for culture results to start antibiotics - mortality increases with delayed treatment in neutropenic fever 1.

Do not rely solely on negative CRP - while helpful prognostically, it does not exclude infection in this setting 4.

Do not perform rectal examination - avoid rectal temperatures and examinations during neutropenia 1.

Duration of Therapy

• If ANC recovers to ≥500/µL, afebrile for 48 hours, and cultures negative: Stop antibiotics 1
• If ANC remains <500/µL but afebrile for 5-7 days with no complications: Can stop antibiotics in low-risk patients 1
• Continue antibiotics for minimum 7 days if organism identified, adjusting to targeted therapy 1