Treatment of Febrile Neutropenia
Immediate empirical antimicrobial treatment with broad-spectrum antibiotics must be started within the first hour of fever onset in neutropenic patients to reduce mortality. 1
Initial Assessment and Risk Stratification
Before selecting therapy, risk stratification is essential:
Low-risk patients (all criteria must be met):
- Outpatient status at fever onset
- No significant comorbidities
- Anticipated neutropenia duration ≤7 days
- ANC >100 cells/mm³
- Monocyte count >100 cells/mm³
- Normal chest radiograph
- Normal renal and hepatic function
- Expected neutrophil recovery within 10 days
- No catheter-site infection
- Early evidence of bone marrow recovery
- Malignancy in remission 1
High-risk patients (any of the following):
- Inpatient status
- Significant comorbidities
- Anticipated neutropenia >7 days
- ANC <100 cells/mm³
- History of recent bone marrow transplantation
- Hypotension at presentation
- Underlying hematologic malignancy
- Severe or prolonged neutropenia 2
Empirical Antimicrobial Therapy
Low-risk patients:
- Oral therapy option: Ciprofloxacin plus amoxicillin-clavulanate 1
- IV monotherapy option: Cefepime, ceftazidime, or piperacillin/tazobactam 1
High-risk patients:
- IV monotherapy (preferred): Meropenem, imipenem/cilastatin, or piperacillin/tazobactam 1
- Alternative: Ceftazidime or cefepime 1, 2
- Cefepime dosing: 2g IV every 8 hours 2
Special considerations:
- If suspected catheter-related infection or resistant organisms: Add vancomycin (glycopeptide) 1
- If severe sepsis: Consider adding aminoglycoside despite increased renal toxicity 1
- For suspected meningitis: Ceftazidime plus ampicillin or meropenem 1
Monitoring and Reassessment at 48-72 Hours
If afebrile and ANC ≥0.5×10⁹/L at 48 hours:
- Low-risk: Consider switching to oral antibiotics 1
- High-risk: If on dual therapy, aminoglycoside may be discontinued 1
- When pathogen identified: Continue appropriate specific therapy 1
If still febrile at 48 hours:
- If clinically stable: Continue initial antibacterial therapy 1
- If clinically unstable: Broaden antibiotic coverage based on clinical developments 1
- Consider adding antifungal therapy if fever persists beyond 4-6 days 1
Duration of Therapy
- If ANC ≥0.5×10⁹/L, patient asymptomatic, afebrile for 48 hours, and negative blood cultures: Discontinue antibiotics 1
- If ANC <0.5×10⁹/L, no complications, and afebrile for 5-7 days: Discontinue antibiotics 1
- Exception: High-risk cases with acute leukemia or post-high-dose chemotherapy may continue antibiotics for up to 10 days or until ANC ≥0.5×10⁹/L 1
Management of Cardiovascular Complications
For sepsis-induced hypotension:
- Initial management: Volume resuscitation with crystalloids or colloids 1
- Target parameters: Mean arterial pressure ≥65 mmHg, central venous pressure 8-12 mmHg, urinary output ≥0.5 ml/kg/h 1
- If hypotension persists: Add norepinephrine (0.1-1.3 μg/kg/min) 1
Common Pitfalls to Avoid
Delayed antibiotic initiation: Each hour of delay in antimicrobial administration over the first 6 hours is associated with a 7.6% decrease in survival 1
Inappropriate empiric coverage: Local microbiology data and resistance patterns should guide antibiotic selection 1
Overuse of vancomycin: Should not be used routinely but reserved for specific indications (suspected catheter-related infection, resistant organisms) 1
Inadequate monitoring: Daily assessment of fever trends, bone marrow function, and renal function is essential until resolution 1
Prolonged therapy: Continuing antibiotics unnecessarily increases risk of resistance and adverse effects 1