Workup for Febrile Neutropenia
The initial workup for a febrile neutropenic patient must include immediate blood cultures from peripheral veins and any indwelling catheters, followed by prompt initiation of empirical broad-spectrum antimicrobial therapy within 1 hour of presentation, regardless of clinical stability. 1
Initial Assessment
Immediate Evaluation
- Assess circulatory and respiratory function with vigorous resuscitation if needed
- Careful examination for potential infection foci (even minimal signs are significant)
- Obtain the following diagnostic tests:
- Complete blood count with differential
- Blood cultures (peripheral and from all indwelling catheters)
- Chest radiograph
- Liver and kidney function tests
- Cultures from suspected infection sites 2
Specific Sites to Examine
- Periodontium
- Pharynx
- Esophagus
- Lung
- Perineum
- Skin
- All catheter insertion sites 2
Risk Stratification
Use the Multinational Association for Supportive Care in Cancer (MASCC) index to assess risk:
- Score ≥21 indicates low-risk (6% complication rate, 1% mortality)
- Score <21 indicates high-risk 1
Key MASCC criteria include:
- Burden of illness (mild vs. moderate-severe symptoms)
- Absence of hypotension
- Absence of COPD
- Solid tumor or no previous fungal infection
- Outpatient status at onset of fever
- Age <60 years 1
Empiric Antibiotic Therapy
High-Risk Patients
- Monotherapy with anti-pseudomonal beta-lactam:
Special Considerations
Add vancomycin ONLY if:
- Suspected catheter-related infection
- Known colonization with resistant gram-positive organisms
- Positive blood cultures for gram-positive bacteria
- Hypotension 2
For pneumonia:
- Add a macrolide to cover atypical organisms 1
For intra-abdominal/pelvic infection:
- Add metronidazole 1
Monitoring and Follow-up
Daily Assessment
- Clinical evaluation (every 2-4 hours if unstable)
- Daily monitoring of:
- Fever trends
- Complete blood count
- Renal function 1
Assessment at 48 Hours
If afebrile and ANC ≥0.5×10^9/L:
- Low-risk: Consider changing to oral antibiotics
- High-risk: If on dual therapy, aminoglycoside may be discontinued
- When pathogen identified: Continue appropriate specific therapy 1
If still febrile at 48 hours:
- Clinically stable: Continue initial antibacterial therapy
- Clinically unstable: Broaden antibiotic coverage and seek infectious disease consultation 1
Antifungal Considerations
- If fever persists >4-6 days, consider initiating antifungal therapy
- Perform chest CT scan before starting antifungals to look for typical changes
- Options include:
- Liposomal amphotericin B
- Echinocandin (caspofungin)
- Fluconazole (if low risk for aspergillosis and no prior azole prophylaxis) 1
Duration of Therapy
If ANC ≥0.5×10^9/L, afebrile for 48h, and negative cultures:
- Discontinue antibiotics 1
If ANC <0.5×10^9/L but clinically stable and afebrile for 5-7 days:
- Discontinue antibiotics
- Exception: high-risk cases (acute leukemia, post-high-dose chemotherapy) may continue for up to 10 days or until ANC ≥0.5×10^9/L 1
Common Pitfalls to Avoid
- Delayed antibiotic administration - Must give within 1 hour of presentation 2
- Inappropriate vancomycin use - Reserve for specific indications 2
- Inadequate assessment of infection sites - Neutropenic patients may have subtle symptoms 2
- Underestimating infection risk - Risk significantly increases when ANC falls below 0.5×10^9/L 2
- Continuing broad-spectrum antibiotics unnecessarily - De-escalate therapy based on culture results and clinical response 4
Special Situations
Suspected Meningitis or Encephalitis
- Perform lumbar puncture
- For bacterial meningitis: ceftazidime plus ampicillin (to cover Listeria) or meropenem
- For viral encephalitis: high-dose acyclovir 1
Persistent Fever Despite Neutrophil Recovery
- Consult infectious disease specialist
- Consider antifungal therapy 1