Key Facts

Neutropenic sepsis is the most common life-threatening complication of cancer chemotherapy. It requires immediate empirical antibiotic treatment, as the immunocompromised state allows rapid progression to septic shock and death.

Epidemiology

• Complicates 15-25% of chemotherapy cycles (varies by regimen and patient factors)
• Higher risk with haematological malignancies than solid tumours
• Neutrophil nadir typically occurs 7-14 days after chemotherapy
• Annual incidence in UK cancer patients receiving chemotherapy: approximately 20,000 episodes

Aetiology

• Chemotherapy-induced myelosuppression → neutropenia → impaired innate immunity
• Sources of infection: GI tract (translocation of gut flora), skin (central venous catheter), respiratory tract, urinary tract
• Often no source identified (30-50% of episodes)
• Risk factors: previous neutropenic sepsis, poor performance status, advanced disease, mucositis, central venous catheter, comorbidities (diabetes, COPD, renal impairment)

Pathophysiology

• Neutrophils are the first line of defence against bacterial and fungal infections
• With counts <0.5 × 10⁹/L, risk of serious infection increases exponentially
• <0.1 × 10⁹/L: highest risk; unable to mount inflammatory response (classic signs of infection may be absent)
• Rapid bacterial proliferation can lead to septicaemia, multi-organ dysfunction, and death within hours

Typical Presentation

• Fever ≥38°C (single reading) or ≥37.5°C sustained for >1 hour
• Patient receiving chemotherapy within the last 6 weeks
• May have rigors, sweats, tachycardia
• Signs of sepsis: hypotension, confusion, tachypnoea, oliguria

Atypical Presentation

• Hypothermia (<36°C) may indicate severe sepsis
• Absence of typical inflammatory signs (no erythema, no pus formation) due to neutropenia
• Non-specific symptoms: fatigue, malaise, myalgia

Red Flags

• Systolic BP <90 mmHg
• Temperature >39°C or <36°C
• Heart rate >130/min
• Respiratory rate >25/min
• SpO2 <91%
• Altered mental status
• Lactate >2 mmol/L
• New onset of organ dysfunction

Bedside

• ABCDE assessment
• Full observations including NEWS2 score
• Examine all potential sites: oral cavity, central line exit site, lungs, abdomen, perianal area, skin
• Do NOT perform digital rectal examination (risk of bacteraemia through damaged mucosa)

Bloods

• Blood cultures: at least 2 sets (peripheral + each lumen of central line); BEFORE antibiotics if possible but do NOT delay antibiotics
• FBC (confirm neutropenia)
• U&Es, creatinine (renal function for dose adjustment)
• LFTs
• CRP, lactate
• Coagulation screen (DIC screen if unwell)
• Blood gas

Imaging

• CXR: baseline, even if no respiratory symptoms
• CT if source unclear and patient not improving
• HRCT chest if invasive fungal infection suspected

Special Tests

• MSU, stool cultures (if diarrhoea), sputum culture, wound swabs
• CMV PCR, galactomannan, β-D-glucan if prolonged neutropenia (>7 days) and not responding to antibiotics
• Central line tip culture if line removed

Non-pharmacological

• Immediate assessment using Sepsis 6 bundle
• IV access (large bore)
• Fluid resuscitation with IV crystalloid
• Oxygen to maintain SpO2 ≥94%
• Strict hand hygiene and reverse barrier nursing
• Consider HDU/ITU if haemodynamically unstable

Pharmacological

• Empirical antibiotics within 1 hour (NICE NG151):
  • First-line: piperacillin-tazobactam 4.5g IV TDS (most common UK protocol)
  • Penicillin allergy: meropenem 1g IV TDS
  • Add vancomycin 15-20mg/kg IV BD if: suspected line infection, skin/soft tissue infection, MRSA colonisation, haemodynamic instability
  • Add gentamicin 5-7mg/kg IV if: septic shock (local protocol)
• Escalation: if no improvement at 48 hours, consider broadening spectrum (add antifungal: caspofungin 70mg IV loading then 50mg OD, or liposomal amphotericin B if neutropenia >7 days)
• G-CSF: therapeutic use in established neutropenic sepsis (controversial; consider if prolonged neutropenia expected)
• Step down: to oral antibiotics (co-amoxiclav 625mg TDS + ciprofloxacin 500mg BD) if MASCC ≥21, afebrile >48 hours, and improving

Surgical/Interventional

• Central line removal: if tunnel infection, exit site infection not responding, or persistent bacteraemia
• Drainage of any collections

Referral Criteria

• All suspected neutropenic sepsis: immediate acute oncology or A&E assessment
• Escalation to ITU if: refractory hypotension, multi-organ failure, respiratory failure
• Discussion with microbiology for resistant organisms or failure to respond

• With prompt treatment: mortality 5-10%
• If antibiotics delayed >6 hours: mortality rises to 30-50%
• MASCC score ≥21: low risk (predicted mortality <5%); suitable for early discharge/oral therapy
• MASCC score <21: high risk (mortality 10-36%); requires inpatient IV antibiotics
• Most episodes resolve within 5-7 days
• Prolonged neutropenia (>7 days): increased risk of invasive fungal infection (aspergillosis, candidiasis)

MASCC Risk Index

Neutropenic Sepsis Antibiotic Escalation