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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Definition: temperature ≥38°C (or clinical signs of sepsis) AND neutrophils <0.5 × 10⁹/L (or expected to fall to <0.5) — most commonly after cytotoxic chemotherapy
- Medical EMERGENCY: administer empirical IV antibiotics within 60 MINUTES of presentation (NICE CG151)
- First-line antibiotic: piperacillin-tazobactam (Tazocin) 4.5 g IV — covers Gram-negative including Pseudomonas
- Fever persisting >48-72 hours despite antibiotics: consider empirical antifungal (liposomal amphotericin B or caspofungin)
- MASCC score predicts risk: low-risk patients may be managed as outpatient with oral antibiotics (amoxicillin-clavulanate + ciprofloxacin)
Overview
Neutropenic sepsis (febrile neutropenia) is an oncological emergency occurring when patients with chemotherapy-induced bone marrow suppression develop fever. The severely depleted neutrophil count means the normal inflammatory response is blunted — patients may have minimal localising signs despite life-threatening infection. Without prompt empirical antibiotic treatment, mortality is >50%. The classic teaching is that the absence of pus or inflammatory signs does NOT exclude serious infection in a neutropenic patient.
Epidemiology
Neutropenic sepsis affects approximately 10-50% of patients receiving cytotoxic chemotherapy, depending on the regimen intensity. It is the most common life-threatening complication of cancer chemotherapy. Mortality ranges from 5% in low-risk patients to >20% in high-risk patients (prolonged neutropenia, haematological malignancy, significant comorbidities). The risk is highest with intensive regimens for AML, ALL, and during stem cell transplant conditioning.
Clinical Features
Symptoms
Fever ≥38°C — may be the ONLY sign. Some patients may be hypothermic (worse prognosis)
Rigors (suggest bacteraemia)
Malaise, fatigue
Sore throat, mouth ulcers (mucositis — common entry point for organisms)
Perianal pain (perianal abscess — avoid PR examination in neutropenic patients)
Cough, dyspnoea (pneumonia — CXR may be NORMAL due to absence of neutrophils to mount inflammatory infiltrate)
Signs
Fever (or hypothermia)
Tachycardia, hypotension (septic shock)
Minimal localising signs — pus does NOT form without neutrophils
Mucositis (oral erythema, ulceration)
Central line site: erythema or discharge (catheter-related bloodstream infection)
Perianal erythema or tenderness (DO NOT perform PR examination)
Investigations
First-line
FBCNeutrophils <0.5 × 10⁹/L (or <1.0 and expected to fall). Document nadir timing post-chemotherapy
Blood cultures (peripheral AND from central line if present)At LEAST 2 sets before antibiotics — but do NOT delay antibiotics to obtain cultures
Lactate, U&Es, LFTs, CRPAssess organ function and severity. Lactate >2 mmol/L = sepsis, >4 = septic shock
Second-line
Urine MC&SUTI is a common source, even without symptoms
CXRMay be NORMAL early (neutropenia prevents formation of inflammatory infiltrate). Repeat if clinical concern persists
Stool sample for C. difficile toxinIf diarrhoea — antibiotics and chemotherapy both increase C. diff risk
SwabsLine site, wound, throat, and any suspicious skin lesions
Specialist
CT chest (HRCT)If persistent fever >4-5 days without source — look for invasive pulmonary aspergillosis ("halo sign")
Galactomannan and beta-D-glucanFungal biomarkers — send if invasive fungal infection suspected
MASCC scoreMultinational Association for Supportive Care in Cancer risk index. Score ≥21 = low risk (may be suitable for outpatient management)
Management
NICE CG151 (Neutropenic Sepsis, 2012)1
Immediate management — within 60 minutes (NICE CG151)
- Start empirical IV broad-spectrum antibiotic WITHIN 60 MINUTES of presentation — this is a key performance standard
- First-line: piperacillin-tazobactam (Tazocin) 4.5 g IV QDS — covers Gram-negative including Pseudomonas
- If penicillin allergy: meropenem 1g IV TDS
- If central line present: do NOT remove empirically — line removal only if confirmed line infection or patient deteriorating
2
If not responding within 48 hours
- Reassess: repeat cultures, imaging, consider switching antibiotic (e.g. add meropenem or glycopeptide)
- Add vancomycin/teicoplanin if: central line infection suspected, severe mucositis, skin/soft tissue infection, known MRSA colonisation
- Review at 48 hours: still febrile → consider changing antibiotic class, adding antifungals
3
Empirical antifungals (persistent fever >4-5 days)
- If fever persists >4-5 days despite broad-spectrum antibiotics: consider empirical antifungal
- Liposomal amphotericin B (AmBisome) or caspofungin — covers Aspergillus and Candida
- HRCT chest to look for invasive aspergillosis
4
Low-risk outpatient management
- Selected low-risk patients (MASCC ≥21, expected short duration of neutropenia, no significant comorbidities): can be managed with oral antibiotics
- Oral regimen: amoxicillin-clavulanate (co-amoxiclav) + ciprofloxacin
- Close follow-up and safety net — admit if deteriorating
5
G-CSF
- G-CSF (filgrastim, pegfilgrastim): not routinely recommended for treatment of established neutropenic sepsis (NICE CG151)
- Used for PRIMARY PROPHYLAXIS with subsequent chemotherapy cycles if previous neutropenic sepsis or high-risk regimen (≥20% risk)
Complications
- Septic shock: Mortality >40% in neutropenic patients who develop shock
- Invasive fungal infection: Aspergillus, Candida — major cause of mortality in prolonged neutropenia
- Chemotherapy dose delay/reduction: Neutropenic sepsis may necessitate dose modifications, potentially compromising cancer treatment efficacy
- Multi-organ failure: From uncontrolled sepsis
UKMLA Exam Tips
- 1IV antibiotics within 60 MINUTES — this is the single most important management point for neutropenic sepsis (NICE CG151)
- 2Piperacillin-tazobactam (Tazocin) is first-line — know this drug. Covers Pseudomonas
- 3Normal CXR does NOT exclude pneumonia in a neutropenic patient — no neutrophils = no infiltrate
- 4Do NOT perform PR examination in a neutropenic patient — risk of introducing infection through compromised mucosa
- 5Fever may be the ONLY sign of sepsis — neutropenic patients cannot mount a normal inflammatory response
- 6Persistent fever >4-5 days despite antibiotics = think invasive FUNGAL infection (Aspergillus) → CT chest + antifungals
practicetest your knowledge on neutropenic sepsisApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — haematology and beyond.
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