Febrile neutropenia

Definition

• Fever: temperature ≥38.3°C once, or ≥38ºC sustained for at least one hour
• Neutropenia: absolute neutrophil count (ANC) < 1×10^9^/L
  • Severe neutropenia: ANC < 0.5×10^9^/L, or expected to decrease below 0.5×10^9^/L within the next 48 hours
  • Profound neutropenia: ANC < 0.1×10^9^/L

Clinical Manifestations

• Fever
• Signs/symptoms of any infection:
  • Oropharynx
  • Chest
  • Skin
  • Anus

Different Diagnosis

• No focus is identified and no cultures isolated in about half of cases
  • When a focus is identified: respiratory > bloodstream > urinary > SSTI/GI/other
• Cultures
  • Gram-negative: E. coli > Pseudomonas > Klebsiella > others
  • Gram-positive: Coag-neg Staph > Staph aureus > Enterococcus > other
  • Fungi: Candida (bloodstream), Aspergillus (heme malignancies)

Epidemiology

• 80% of patients receiving chemotherapy have at least one episode of febrile neutropenia
• Genetic predisposition like mannose-binding lectin deficiency doubles the duration of fever

Investigations

• Blood cultures from all lines, including central lines, repeated at least every 72h if it continues
• Urinalysis +/- urine culture
• CXR regardless of symptoms
• Nasopharyngeal swab for respiratory viruses
• Stool for C.diff, if appropriate
• If ongoing fevers, consider CT chest

Management

• In general, broad-spectrum antimicrobials until fever resolved x48h AND neutrophils > 0.5 AND minimum course of 5-7 days, then consider stepping down to treat underlying infection only
• Empiric antibiotic choice depends on site but should include pseudomonal coverage
  • Piptazo 4.5g q8h, Ceftazidime 2g q8h, Ciprofloxacin 400 q12h and gentamicin 5-7mg/kg q24h, Meropenem 1g q8h
• Consider adding other agents empirically if concern for:
  • MRSA or SSTI or severe mucositis or septic shock: vancomycin 15mg/kg q12h, reassessed at 48h
  • Typhlitis: ensure adequate anaerobic coverage, may need to add metronidazole 500mg q12h
  • VRE: linezolid or daptomycin
  • ESBL: carbapenem
  • KPC: polymixin-colistin or tigecycline
• If still febrile and neutropenic for 4 to 7 days despite antibiotics, add antifungal (especially if not on prophylaxis)
  • Caspofungin 70mg then 50mg daily
  • Liposomal amphotericin B 3mg/kg daily
  • Anidulafungin if renal or hepatic dysfunction
• In high-risk patients, can consider adding GCSF (Neupogen/Filgrastim)
• In some low-risk patients, can step down to amoxicillin-clavulanic acid AND ciprofloxacin 750
  • Expected duration of severe neutropenia ≤7 days, AND
  • No comorbidities or significant hepatic or renal dysfunction
  • Mostly, these patients are receiving chemotherapy for solid tumours
• Monitor for myeloid reconstitution syndrome (similar to IRIS) while neutrophils are recovering

Resources

• MASCC risk calculator

Further Reading

• IDSA 2011