What is the management plan for a patient with neutropenia?

Management of Neutropenia

All patients with fever and neutropenia must receive empirical broad-spectrum antibiotics within 2 hours of presentation, as infection can progress rapidly and delay substantially worsens outcomes. 1

Initial Risk Stratification

Risk stratification is the critical first step that determines the entire management pathway:

• Classify neutropenia severity by absolute neutrophil count (ANC): 2

  • Mild: ANC 1.0-1.5 × 10⁹/L
  • Moderate: ANC 0.5-1.0 × 10⁹/L
  • Severe: ANC <0.5 × 10⁹/L (or <100 cells/µL for highest risk)

• For cancer patients with fever and neutropenia, use the MASCC score to stratify risk: 1

  • High-risk: MASCC score <21, or anticipated prolonged neutropenia (>7 days), or ANC <100 cells/µL
  • Low-risk: MASCC score ≥21, or anticipated brief neutropenia (<7 days) with few comorbidities

Immediate Evaluation and Management

Clinical Assessment

Within 2 hours of presentation with fever, perform: 1

• Complete history focusing on: duration of neutropenia, recent chemotherapy, prior infections, indwelling catheters, specific symptoms (respiratory, gastrointestinal, skin lesions, perineal pain) 1
• Physical examination emphasizing: skin (especially perineum and catheter sites), oropharynx, lungs, abdomen, perirectal area 1
• Avoid rectal examination, rectal thermometers, enemas, and suppositories—these are contraindicated 1

Diagnostic Workup

Obtain immediately: 1

• At least 2 sets of blood cultures (from peripheral vein and each lumen of central venous catheter if present) 1
• Complete blood count with differential and platelet count 1
• Comprehensive metabolic panel 1
• Chest radiograph (or chest CT if pulmonary symptoms present) 1
• Urinalysis and urine culture 1
• For any skin lesions: biopsy or aspiration for histology, cytology, and culture 1

Empirical Antibiotic Therapy

Initiate within 2 hours for all febrile neutropenic patients: 1

• High-risk patients: Hospitalize and start IV vancomycin plus antipseudomonal antibiotics (cefepime, meropenem, or imipenem) 1
• Low-risk patients: May consider outpatient management with close follow-up in select cases 1
• Continue antibiotics until neutropenia resolves (ANC >500 cells/mm³) even if fever resolves earlier 1

Antimicrobial Prophylaxis

Antibacterial Prophylaxis

• Start with onset of neutropenia: Levofloxacin or ciprofloxacin 500 mg orally daily 1
• Continue until: ANC >500 cells/mm³ 1

Antiviral Prophylaxis

• Start with chemotherapy: Acyclovir 400 mg or valacyclovir 500 mg orally twice daily 1
• Continue for: 6 months post-treatment (minimum 3 months) or until CD4 count >200 cells/mm³ 1

Antifungal Prophylaxis

• Start on day of cell infusion (for transplant patients) or with severe neutropenia: Fluconazole 400 mg orally daily 1
• Continue until: ANC >1000 cells/mm³ 1

Pneumocystis Prophylaxis

• Start with chemotherapy: Trimethoprim-sulfamethoxazole orally three times per week 1
• Continue for: 6 months (minimum 3 months) or until CD4 count >200 cells/mm³ 1

Granulocyte Colony-Stimulating Factor (G-CSF) Use

When to Use G-CSF

G-CSF (filgrastim) is indicated for: 3

• Severe neutropenia (ANC <500 cells/mm³) with fever: Start filgrastim 5 mcg/kg/day subcutaneously 3
• Primary prophylaxis: When chemotherapy regimen has >20% risk of febrile neutropenia 1, 4
• Post-chemotherapy: Begin at least 24 hours after chemotherapy completion 3
• Post-bone marrow transplant: Start 10 mcg/kg/day IV at least 24 hours after transplant 3

When NOT to Use G-CSF

Do not routinely use G-CSF for: 1

• Afebrile neutropenic patients (no clinical benefit demonstrated) 1
• Within 24 hours before chemotherapy 3
• Patients with ANC >10,000/mm³ 3

G-CSF Administration Details

• Continue until: ANC reaches 10,000/mm³ following expected nadir, or for up to 2 weeks 3
• Monitor: CBC twice weekly during therapy 3
• For post-transplant patients: Titrate dose based on ANC response, reducing to 5 mcg/kg/day when ANC >1000/mm³ for 3 consecutive days 3

Infection Prevention Measures

Hand Hygiene and Isolation

• Hand hygiene is the single most effective infection prevention measure—mandatory before entering and after leaving patient rooms 1, 2
• Standard barrier precautions for all patients 1
• HSCT recipients require private rooms with >12 air exchanges/hour and HEPA filtration 1

Skin and Oral Care

Daily hygiene practices: 1

• Daily showers or baths to optimize skin integrity 1
• Daily inspection of perineum and catheter sites 1
• Gentle perineal cleaning after bowel movements, thorough drying after urination 1
• Females wipe front to back; avoid tampons during menstruation 1

Oral care: 1

• Brush teeth at least twice daily with soft toothbrush 1
• Oral rinses 4-6 times daily with sterile water, saline, or sodium bicarbonate (especially with mucositis) 1
• Daily flossing if accomplished without trauma 1

Environmental Precautions

Avoid in hospital rooms: 1

• Plants, dried flowers, and fresh flowers (harbor Aspergillus and Fusarium) 1
• Household pets 1

Diet: 1

• No specific "neutropenic diet" required—well-cooked foods acceptable 1
• Well-cleaned raw fruits and vegetables are acceptable 1
• Avoid prepared luncheon meats 1

Monitoring and Follow-Up

For Moderate Neutropenia (ANC 0.5-1.0 × 10⁹/L)

• Monitor CBC: Weekly initially, then every 2-4 weeks once stable 2
• Educate patients to recognize and immediately report fever, chills, or signs of infection 2

For Severe Neutropenia (ANC <0.5 × 10⁹/L)

• Monitor CBC: At least twice weekly during active treatment 1, 3
• Platelet transfusions: Maintain platelets >30,000/mm³ (use only irradiated blood products) 1
• Red blood cell transfusions: Maintain hemoglobin ≥7.0 g/dL 1

Common Pitfalls to Avoid

• Never delay antibiotics waiting for culture results in febrile neutropenia—outcomes worsen significantly with delays beyond 2 hours 1
• Do not perform rectal examinations, use rectal thermometers, enemas, or suppositories in neutropenic patients 1
• Avoid using G-CSF in afebrile neutropenic patients—no clinical benefit and increases cost 1
• Do not restrict diet unnecessarily—neutropenic diets show no benefit in preventing infections 1, 2
• Never administer G-CSF within 24 hours before chemotherapy 3
• Do not overlook skin lesions—biopsy even small lesions as they may represent disseminated infection 1