febrile neutropenia

oncologic emergency

Definition:

• Fever: Oral temp $>38.3^{\circ }C$ single reading OR $\ge 38.0^{\circ }C$ sustained for $>1$ hour.
• Neutropenia: ANC $<0.5\times 10^9/L$ or expected to fall below this level within 48 hours.

risk stratification (mascc score)

Determine site of care (Inpatient vs Outpatient).

• MASCC Score $\ge 21$: Low Risk (Outpatient management candidate with PO Cipro/Amox-Clav).
• MASCC Score $<21$: High Risk (Inpatient admission required).
  • Factors reducing score: Hypotension, COPD, Solid tumour (vs heme), Age $>60$, Dehydration, Severity of symptoms.

immediate management (the 1-hour bundle)

1. Cultures:
   • Min 2 sets: 1 peripheral + 1 from CVC (each lumen if possible).
2. Source Control:
   • Clinical exam: Oropharynx, catheter sites, lungs, perianal inspection.
   • NO DRE (risk of mucosal tear/translocation).
   • Imaging: CXR discouraged (low sensitivity); low-dose chest CT preferred if respiratory symptoms.
3. Antibiotics: Initiate empirical monotherapy within 60 minutes of presentation.

antibiotic protocols

local variation

Protocols vary significantly by institution based on local resistance patterns. Always check your local guidelines.

Standard First Line (High Risk / Inpatient)

• Imipenem 500 mg IV q6h.
• Note: Lowers seizure threshold (caution in CNS disease).
• Alternative: Piperacillin-Tazobactam 4.5 g IV q6h (Severe infection dose). Note: 3.375 g is insufficient for FN.

Penicillin Allergy (Severe)

• Vancomycin + Ciprofloxacin 400 mg IV q8h. (Or Aztreonam + Vanc).

Indications to ADD Upfront Vancomycin Avoid routine use (ASCO/IDSA 2018). Add only if:

1. Haemodynamic instability (septic shock).
2. Known MRSA colonization.
3. Clinically apparent line infection (inflamed tunnel/exit site).
4. Gram-positive cocci on preliminary blood culture stat.
5. Pneumonia (Radiologically confirmed).

Resistant Organisms (Specific Additions)

• VRE History: Add Linezolid or Daptomycin.
• ESBL History: Early escalation to Carbapenems.
• KPC (Carbapenemase): Consult ID (Colistin / Ceftazidime-Avibactam / Cefiderocol).

exam trap

“Double coverage” for Pseudomonas (e.g., Beta-lactam + Aminoglycoside) is NOT routinely indicated unless septic shock or high local resistance rates.

reassessment & escalation (72-96 hours)

Persistent Fever in Stable Patient

• Do not switch antibiotics solely for persistent fever if stable.
• Diagnostics: Repeat blood cultures only if clinical deterioration or new fever spike; routine repeats discouraged. Consider Chest/Abdo CT or PET-CT to rule out occult source.

Clinical Deterioration

• Escalate to Meropenem (if on Pip-Taz) + Vancomycin.

Fungal Coverage (The “Pre-emptive” Shift)

• Trigger: Persistent fever $\ge 96h$ (4 days) despite broad-spectrum Abx.
• Strategy:
  • Preferred: Pre-emptive approach (Biomarkers: Galactomannan + Chest CT). Initiate antifungal only if positive.
  • Alternative: Empiric antifungal (if no rapid diagnostics).
• Agents:
  • Mould-active: Liposomal Amphotericin B, Voriconazole, or Caspofungin.

de-escalation & duration

evidence update (agiho 2024 vs asco 2018)

Newer Evidence (AGIHO 2024 / NCCN 2025): Empirical antibiotics can be discontinued after 72–96 hours of apyrexia and clinical recovery IRRESPECTIVE of neutrophil count.

Traditional Approach (ASCO 2018): Continue antibiotics until ANC $>0.5$. Current practice is shifting towards the newer, restrictive approach, but ~50% of centres still follow the traditional rule.

• Documented Infection: Treat for standard duration of specific infection (e.g., 7-14 days).
• FUO (Fever of Unknown Origin): Stop after 3-5 days afebrile + stable.

special considerations

exam pearl: catheter removal

• Coag-negative Staph (CONS): Retain line, treat systemically.
• Staph aureus / Candida / Pseudomonas / Mycobacteria: Prompt removal recommended.
  • Nuance: In severe thrombocytopenia or coagulopathy, removal may be delayed until safe, but source control is critical for these organisms.
• Tunnel/Pocket infection: REMOVE line.

red flag: viral pneumonia

In patients with respiratory symptoms/infiltrates, consider viral testing (Multiplex PCR). Bronchoscopy (BAL) is mandatory if infiltrates suspected to be IFI (Invasive Fungal Infection).