Infectious DiseasesTier 1Disease (DEADMAN)

Febrile neutropenia

Description

Fever (single temp >=38.3C, or >=38.0C sustained over 1 hour) with neutrophil count <0.5x10^9/L (or <1.0 and expected to fall)
A medical emergency - empirical treatment starts before an organism is identified

Complicates chemotherapy across solid and haematological malignancy, most severe with intensive haematological regimens
Mortality ~2-5% with prompt treatment, substantially higher with delay or high-risk features
No identifiable organism in ~50-60% of episodes despite thorough work-up

Chemotherapy-induced mucosal barrier injury + neutropenia -> translocation of endogenous gut/skin flora
Gram-negative bacilli (E. coli, Klebsiella, Pseudomonas aeruginosa) - most concerning for rapid deterioration
Gram-positive cocci (coagulase-negative staphylococci, viridans streptococci, S. aureus) - increasingly common, especially line-associated
Fungal (Candida, Aspergillus) - consider with prolonged neutropenia (>7-10 days) or persistent fever despite broad-spectrum antibiotics

A. Risk stratification - MASCC score determines pathway

MASCC >=21 = low risk (may be suitable for early discharge/oral therapy in selected, well patients with good social support)
MASCC <21 or clinical high-risk features (haemodynamic instability, poorly controlled cancer, pneumonia, GI symptoms, anticipated prolonged/profound neutropenia) - admit for IV therapy

B. Work-up (done rapidly, without delaying antibiotics)

Blood cultures - peripheral AND from each lumen of any central line
FBE, UEC, LFT, CRP, lactate
Site-directed cultures/imaging (urine, sputum, stool, wound, CXR) based on symptoms
Full clinical exam including skin, line sites, perianal region (avoid digital rectal exam - risk of translocation/bacteraemia)

A. Immediate empirical antibiotics - within 1 hour of presentation, before culture results

High-risk/admitted: IV anti-pseudomonal beta-lactam monotherapy (e.g. piperacillin-tazobactam, or a carbapenem, or ceftazidime) - monotherapy equivalent to combination therapy with less toxicity
Add vancomycin if: haemodynamic instability/septic shock, suspected line infection, severe mucositis, known MRSA colonisation, or skin/soft tissue infection
Low-risk, selected outpatient-suitable patients: oral ciprofloxacin + amoxicillin-clavulanate - only if no fluoroquinolone prophylaxis already in use and no localising signs
Tailor to local antibiogram and any known prior resistant organism colonisation

B. Reassessment at 48-72 hours

Persistent fever with no organism identified and stable: continue same empirical regimen, do not reflexively escalate
Persistent fever with clinical deterioration: escalate cover (broaden Gram-negative/anaerobic cover, consider resistant organisms)
Persistent fever beyond 4-7 days despite broad-spectrum antibiotics with ongoing neutropenia: consider empirical antifungal therapy (e.g. an echinocandin or a mould-active azole) and imaging for occult fungal infection

C. Line management

Remove line if: septic shock, tunnel/exit site infection, persistent bacteraemia despite therapy, or specific organisms poorly cleared without removal (S. aureus, Candida, resistant Gram-negatives)

D. Growth factors

G-CSF - not routine for treatment of established febrile neutropenia, but used prophylactically in future cycles for patients at high risk of recurrent neutropenic fever

E. De-escalation and duration

Narrow therapy once organism/sensitivities known
Continue until afebrile and neutrophil recovery (ANC >0.5x10^9/L), or per identified source's own required duration if longer

Intensive chemotherapy regimens (especially AML induction, autologous/allogeneic HSCT conditioning)
Central venous access devices
Mucositis, prior colonisation with resistant organisms
Prolonged/profound neutropenia (>7-10 days, ANC <0.1x10^9/L)

Prompt empirical therapy is the strongest modifiable outcome determinant - delay materially increases mortality
Progression to septic shock, especially with Gram-negative bacteraemia, can be rapid
Prolonged neutropenia increases risk of invasive fungal disease
Recurrent febrile neutropenia across chemotherapy cycles may prompt dose reduction, regimen change, or prophylactic G-CSF/antimicrobial strategies for subsequent cycles

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