Febrile neutropenia / neutropenic fever

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

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)

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

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

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 amox/clav AND cipro 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