Treatment of Febrile Neutropenia
Immediate empiric antibiotic therapy with an anti-pseudomonal beta-lactam monotherapy is the recommended first-line treatment for febrile neutropenia, with specific modifications based on risk stratification and clinical response. 1
Initial Assessment and Risk Stratification
- Obtain blood cultures from peripheral vein and all indwelling catheters before starting antibiotics 1
- Risk stratification should guide treatment approach:
Antibiotic Selection
First-Line Therapy
- Monotherapy with anti-pseudomonal beta-lactam is recommended for most patients with febrile neutropenia 1
- Options include:
High-Risk Patients
- Consider combination therapy for high-risk patients (including anti-pseudomonal beta-lactam plus aminoglycoside) 1
- Patients with history of recent bone marrow transplantation, hypotension, underlying hematologic malignancy, or severe/prolonged neutropenia may not respond adequately to monotherapy 2
Additional Coverage Considerations
- Add vancomycin for suspected catheter-related infection, skin/soft tissue infection, pneumonia, or hemodynamic instability 1
- For suspected bacterial meningitis, use ceftazidime plus ampicillin (to cover Listeria monocytogenes) or meropenem 5
Assessment of Response and Subsequent Management
- Perform daily assessment of fever trends, bone marrow and renal function until the patient is afebrile and ANC ≥0.5×10⁹/L 5, 1
- Reassess response to therapy at 48 hours 1
If Patient is Afebrile at 48 Hours with ANC ≥0.5×10⁹/L:
- Low-risk patients with no identified cause: consider changing to oral antibiotics 5, 1
- High-risk patients with no identified cause: if on dual therapy, aminoglycoside may be discontinued 5
- When specific cause is found: continue appropriate targeted therapy 5
If Patient Remains Febrile at 48 Hours:
- If clinically stable: continue initial antibacterial therapy 5
- If clinically unstable: broaden antibiotic coverage or rotate antibiotics 5
- Consider adding glycopeptide (vancomycin) if not already included 5
- Seek expert advice from infectious disease physician or clinical microbiologist for deteriorating patients 5
Antifungal Therapy
- Consider antifungal therapy when fever persists for >4-6 days despite antibacterial therapy 5, 1
- For presumed aspergillosis (based on CT findings), use voriconazole or liposomal amphotericin B 5
- These antifungals can be combined with an echinocandin in unresponsive disease 5
Duration of Therapy
- If neutrophil count ≥0.5×10⁹/L, patient is asymptomatic and has been afebrile for 48 hours, and blood cultures are negative: discontinue antibiotics 5, 1
- If neutrophil count remains ≤0.5×10⁹/L but patient has been afebrile for 5-7 days without complications: consider discontinuing antibiotics 5, 1
- For high-risk cases with acute leukemia and following high-dose chemotherapy: continue antibiotics for up to 10 days, or until neutrophil count is ≥0.5×10⁹/L 5
Special Considerations
- For suspected viral infections: initiate aciclovir after appropriate samples are taken 5
- For suspected cytomegalovirus infection: substitute ganciclovir 5
- For persistent fever despite neutrophil recovery: consult infectious disease physician or clinical microbiologist and consider antifungal therapy 5
Common Pitfalls to Avoid
- Delaying antibiotic therapy - start antibiotics within 1 hour of presentation 1
- Unnecessary continuation of broad-spectrum antibiotics in patients who have recovered from neutropenia and are afebrile 1
- Failure to consider non-bacterial causes of persistent fever (fungal infections, viral infections, drug fever) 1
- Inadequate dosing of antibiotics - some evidence suggests more frequent dosing may be beneficial (e.g., cefepime 1g every 6h vs 2g every 8h) 6