What is the treatment for sepsis neutropenica (febrile neutropenia)?

Treatment of Sepsis Neutropenica (Febrile Neutropenia)

Immediate broad-spectrum antibiotic therapy must be started within 1 hour of presentation in neutropenic patients with fever to reduce mortality, as each hour of delay increases mortality by 7.6%. 1

Diagnostic Evaluation

Before or concurrent with antibiotic administration:

• Complete blood count with differential
• Blood cultures (at least two sets, including one from each lumen of central venous catheter if present)
• Comprehensive metabolic panel
• Chest radiography (for all patients with respiratory symptoms)
• Additional cultures from suspected infection sites (urine, sputum, skin lesions) 1

Risk Stratification

Categorize patients as high-risk or low-risk:

High-Risk Features:

• Profound neutropenia (ANC <100 cells/mm³) expected to last >7 days
• MASCC score <21
• Hemodynamic instability
• Oral/GI mucositis
• New pulmonary infiltrates
• History of recent bone marrow transplantation
• Underlying hematologic malignancy 1

Low-Risk Features:

• Brief expected neutropenia (<7 days)
• MASCC score ≥21
• Few comorbidities 1

Antimicrobial Treatment Algorithm

Step 1: Immediate Empiric Antibiotic Therapy (within 1 hour)

First-line options (monotherapy):

• Meropenem or imipenem/cilastatin or piperacillin/tazobactam 2, 1
• Cefepime (2g IV every 8 hours) is also indicated for empiric treatment of febrile neutropenic patients 3
• Ceftazidime is an alternative option 2

Step 2: Add Additional Agents Based on Clinical Presentation

• For suspected catheter-related infection, known MRSA colonization, severe sepsis, or skin/soft tissue infection:

  • Add vancomycin 1

• For severe sepsis, suspected Pseudomonas infection, or high local resistance patterns:

  • Consider adding an aminoglycoside (despite increased renal toxicity) 2, 1

Step 3: Consider Antifungal Therapy

• If fever persists 3-7 days despite antibiotics, add antifungal therapy:
  • With prior azole exposure: Liposomal amphotericin B or caspofungin
  • For suspected aspergillosis: Voriconazole or liposomal amphotericin B 1

Cardiovascular Support

For sepsis-induced hypotension or lactic acidosis:

1. Volume resuscitation (crystalloid fluids preferred over colloids)

   • Goals: Mean arterial pressure ≥65 mmHg, central venous pressure 8-12 mmHg, urinary output ≥0.5 ml/kg/h 2

2. If hypotension persists despite adequate fluid resuscitation:

   • Add norepinephrine (0.1-1.3 µg/kg/min) 2

Treatment Duration

• For documented infections: Continue antibiotics for at least the duration of neutropenia or 10-14 days, whichever is longer 1
• For unexplained fever: Continue initial regimen until neutrophil recovery (ANC >500 cells/mm³) 1
• For high-risk patients: Continue antibiotics until neutrophil recovery regardless of fever resolution 1

Inpatient vs. Outpatient Management

• High-risk patients: Require inpatient management 1
• Low-risk patients: May be treated as outpatients if they meet specific criteria:
  • No signs of systemic infection
  • Ability to take oral medications
  • Reliable caregiver support and transportation
  • Access to emergency care 1

Implementation Strategies to Improve Outcomes

• Nurse-led protocols for antibiotic administration can significantly improve time to first dose, with studies showing improvement from 67% to 92% of patients receiving antibiotics within 1 hour 4, 5
• Patient-specific directives like Neutropenic Sepsis Alert Cards allow nurses to administer antibiotics without prior medical review 4

Pitfalls and Caveats

1. Attenuated inflammatory signs: Signs and symptoms of inflammation are often diminished or absent in neutropenic patients 1

2. Local resistance patterns: Knowledge of local microbiology data is crucial for selecting antimicrobial agents. Studies show high rates of ESBL-producing organisms (81% of Klebsiella and 60% of E. coli in some settings) 6

3. Lung sepsis challenges: Bacterial lung sepsis in neutropenic patients often lacks microbiological identification. Daptomycin and tigecycline should not be used for suspected lung sepsis in these patients 7

4. Monotherapy limitations: In patients at high risk for severe infection, antimicrobial monotherapy may not be appropriate, particularly for those with history of bone marrow transplantation, hypotension, underlying hematologic malignancy, or severe/prolonged neutropenia 3

5. Human albumin: Should not be used for volume resuscitation as it has not been associated with favorable outcomes 2

The evidence clearly demonstrates that rapid initiation of appropriate antimicrobial therapy is the most critical intervention for improving survival in neutropenic sepsis, with each hour of delay significantly increasing mortality risk.