Synopsis
Recognise infection despite muted inflammatory signs, deliver immediate empirical antibiotics and resuscitation, identify sources and resistant or fungal risk, and select ongoing inpatient or supported ambulatory care safely.
- Suspect neutropenic sepsis in any unwell person receiving or recently receiving systemic anticancer treatment, even when fever and focal inflammatory signs are absent.
- NICE defines it as neutrophils 0.5 × 10^9/L or lower with temperature above 38°C or other clinically significant sepsis features, but treatment begins before the laboratory result when suspicion is credible.
- First-line assessment is simultaneous ABCDE, full observations, lactate, FBC, renal and liver tests and peripheral plus relevant line cultures; sampling must not postpone antibiotic delivery.
- First-line empirical therapy is intravenous piperacillin/tazobactam monotherapy under NICE when allergy, prior resistant organisms and local microbiology do not require an alternative.
- Do not add an aminoglycoside routinely and do not add a glycopeptide solely because a central line is present; each addition needs a defined microbiological or clinical indication.
- Search mouth, skin, line, lungs, abdomen and perianal area gently, but avoid digital rectal examination, suppositories and unnecessary rectal instrumentation during profound neutropenia.
- Use validated risk assessment only after immediate treatment and physiological review; ambulatory care also requires stable organ function, oral absorption, support, transport and rapid 24-hour return.
- Persistent fever during prolonged neutropenia needs CT-based fungal assessment and specialist therapy planning rather than repeated unstructured antibacterial escalation.
Key red flags
Hypotension, rising lactate, mottling, oliguria, confusion, hypoxaemia or respiratory fatigue indicates organ dysfunction and needs senior resuscitation and critical-care review.
A normal temperature does not exclude neutropenic sepsis when corticosteroids, antipyretics or profound immune suppression blunt fever.
Severe abdominal pain, distension or diarrhoea during neutropenia raises neutropenic enterocolitis, perforation and Clostridioides difficile infection.
Perianal pain, line tenderness, oral ulceration or subtle skin change can be the only local clue; avoid rectal examination and instrumentation.
Persistent or recurrent fever during prolonged profound neutropenia despite antibacterial treatment raises invasive fungal infection and requires a new diagnostic strategy.
Rigors, hypotension, tachypnoea, confusion, oliguria or abrupt functional decline after treatment is compatible with neutropenic sepsis despite normal temperature.
Fever with right-sided or diffuse abdominal pain, distension, diarrhoea or bleeding during profound neutropenia raises bowel-wall inflammation, necrosis and perforation.
Ongoing fever, pleuritic pain, haemoptysis, sinus symptoms or CT nodules after several antibacterial days during prolonged neutropenia suggests invasive mould disease.
Investigation priorities
Identify organ dysfunction and establish the urgency and response to resuscitation.
Management branches
Recent anticancer treatment accompanies fever, rigors or clinically important sepsis features.
- Use ABCDE, monitoring and intravenous access; obtain lactate, FBC, renal and liver tests and peripheral plus line cultures without allowing difficult sampling to delay treatment.
- Give the local empirical intravenous regimen immediately, using piperacillin/tazobactam monotherapy when NICE and patient microbiology support it.
- Resuscitate hypoperfusion with repeated assessment, give oxygen for hypoxaemia and escalate shock, respiratory failure or altered consciousness to critical care while searching for source.