What is the management plan for a patient with low neutrophil (white blood cell) count, also known as neutropenia?

Management of Neutropenia

Neutropenic patients require immediate risk stratification based on absolute neutrophil count (ANC) and clinical presentation, with empiric broad-spectrum antibiotics initiated within one hour for febrile neutropenia (ANC ≤500 cells/mm³ with fever ≥38.3°C or ≥38.0°C for 1 hour). 1

Risk Stratification by Neutrophil Count

The severity and infection risk correlate directly with the depth and duration of neutropenia:

• ANC <1000 cells/mm³: Increased susceptibility to infection begins 2
• ANC <500 cells/mm³: Considerably greater infection risk; defines clinically significant neutropenia 2, 1
• **ANC <100 cells/mm³**: Highest risk category with >20% developing bacteremia 1
• Duration matters: Protracted neutropenia (ANC <500 cells/mm³ for ≥10 days) represents a major risk factor for infection 2

High-risk patients include those with anticipated prolonged (>7 days) and profound neutropenia (ANC <100 cells/mm³), MASCC score <21, recent bone marrow transplantation, hypotension at presentation, underlying hematologic malignancy, or severe/prolonged neutropenia 2, 3.

Low-risk patients have anticipated brief (<7 days) neutropenia, ANC >100 cells/mm³, clinical stability, and MASCC score ≥21 2.

Immediate Management of Febrile Neutropenia

Initial Assessment (First Hour)

Obtain blood cultures immediately before antibiotics: At least 2 sets from peripheral vein; if central venous catheter present, obtain one set from catheter lumen(s) and one from peripheral vein 2, 1.

Perform urgent laboratory evaluation: Complete blood count with differential, renal and liver function, coagulation screen, and C-reactive protein 1.

Conduct thorough physical examination focusing on subtle infection signs, as typical inflammatory findings may be absent in severe neutropenia 2. Examine these high-risk sites specifically:

• Periodontium and pharynx
• Lower esophagus
• Lungs (obtain chest radiograph; consider CT if clinically indicated) 2, 1
• Perineum and anus
• Skin (including bone marrow aspiration sites, vascular catheter sites, tissue around nails) 2
• Eye fundus 2

Empiric Antibiotic Therapy

For high-risk patients, initiate IV broad-spectrum antibiotics immediately (within first hour) 2, 1:

Recommended regimens 2, 1, 3:

• Monotherapy: Antipseudomonal beta-lactam (cefepime 2g IV every 8 hours, ceftazidime, carbapenem [imipenem-cilastatin, meropenem, or doripenem], or piperacillin-tazobactam)
• Dual therapy: Antipseudomonal beta-lactam plus aminoglycoside
• Add vancomycin for suspected catheter-related infection, skin/soft tissue infection, hemodynamic instability, or pneumonia 2

Cefepime dosing (FDA-approved for febrile neutropenia) 3:

• Adults: 2g IV every 8 hours for 7 days or until resolution of neutropenia
• Pediatrics (2 months to 16 years, up to 40 kg): 50 mg/kg every 8 hours
• Adjust for renal impairment when creatinine clearance ≤60 mL/min 3

For low-risk patients: May transition to oral antibiotics (ciprofloxacin plus amoxicillin-clavulanate) after initial 48 hours of IV therapy if clinically stable 1.

Duration of therapy: Continue antibiotics until patient is afebrile for 48 hours; in patients whose fever resolves but remain neutropenic beyond 7 days, frequently re-evaluate the need for continued antimicrobial therapy 1, 3.

Granulocyte Colony-Stimulating Factor (G-CSF) Use

Primary prophylaxis with G-CSF is indicated when 2:

• Chemotherapy regimen carries >20% risk of febrile neutropenia
• High-risk patient factors present (age >65, advanced disease, previous febrile neutropenia, poor performance status, no antibiotic prophylaxis)

Therapeutic G-CSF should be considered in febrile neutropenia with 1:

• Predicted worsening course
• Sepsis or tissue infection
• Prolonged neutropenia
• High-risk features (hypotension, pneumonia, invasive fungal infection)

G-CSF dosing 2, 1:

• Filgrastim: 5 mcg/kg/day subcutaneously starting 24-72 hours after last chemotherapy dose until ANC recovery (target ANC >1000 cells/mm³ is sufficient; achieving >10,000 cells/mm³ is unnecessary)
• Pegfilgrastim: 6 mg subcutaneously as single dose or 100 mcg/kg (individualized)

Contraindication: Avoid G-CSF during chest radiotherapy due to increased complications and mortality 2.

Ongoing Monitoring

Daily assessment required until afebrile and ANC ≥500 cells/mm³ 1:

• Fever trends
• Clinical examination for infection signs (remember signs may be minimal or absent) 2, 1
• Bone marrow function
• Renal function

Imaging as clinically indicated: Chest CT for persistent fever or respiratory symptoms; additional imaging for suspected deep tissue infections 2, 1.

Antimicrobial Prophylaxis

For prolonged neutropenia, consider 1:

• Trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis
• Antifungal prophylaxis in high-risk patients with anticipated prolonged profound neutropenia

Critical Pitfalls to Avoid

Do not delay antibiotics waiting for culture results in febrile neutropenia—mortality increases significantly with delayed treatment 1.

Do not rely on typical infection signs: Neutropenic patients may lack induration, erythema, pustulation, pulmonary infiltrates on radiograph, CSF pleocytosis in meningitis, or pyuria in UTI 2.

Do not use G-CSF routinely for treatment of uncomplicated febrile neutropenia—reserve for high-risk situations 2.

Cefepime monotherapy has insufficient data for patients at highest risk (recent bone marrow transplant, hypotension, underlying hematologic malignancy, severe/prolonged neutropenia, septic shock)—consider combination therapy in these patients 3.