Neutropenic sepsis

• Neutropenic sepsis is defined as a neutrophil count of 0.5 × 109 per litre or lower, plus one of the following:

  • Temperature ≥ 38°C or
  • Other signs or symptoms consistent with significant sepsis
• In some hospitals, neutropenic sepsis is diagnosed in patients with a neutrophil count of 1 × 109 per litre or lower. Therefore, local guidelines for the diagnosis and management of neutropenic sepsis should always be followed.
• Pathophysiology:

  • Neutrophils are a key component of the innate immune system and act as the first lone of defence against pathogens
  • Neutropenia impairs the initial inflammatory response to foreign pathogens allowing them to proliferate
  • Many neutropenic patients present with isolated pyrexia as the only clinical evidence of infection
• Causes:

  • Recent chemotherapy - most commonly within 7-10 days
  • Malignant bone marrow infiltration
  • Extensive radiotherapy
  • Bone marrow failure secondary to non-malignant disease e.g. aplastic anaemia
  • Hypersplenism
  • Megaloblastic anaemia
  • Drug induced e.g. clozapine
• Risk factors:

  • Over 60
  • Advanced malignancy
  • Previous neutropenic sepsis
  • Chemotherapy
  • poor performance status
  • Significant co-morbidities
  • Indwelling central venous catheters
  • Corticosteroids
  • prolonged hospital admission
  • Severe or prolonged neutropenia
• There is a clear relationship between both the severity and duration of neutropenia and the risk of developing neutropenic sepsis.
• The Common Terminology Criteria for Adverse Events (CTCAE) grading system can be used to grade the severity of neutropenia
• Patients receiving chemotherapy will be informed of the risk of neutropenic sepsis and advised to contact the oncology team if they develop a fever. Therefore, many patients will present from home with isolated pyrexia.
• neutropenic sepsis may present without fever in some patients, including older patients and those taking immunosuppressive medications such as steroids.
• Typical non-specific symptoms of sepsis include:

  • Fatigue
  • Feeling warm or cold
  • Rigors or shaking
  • Feeling sweaty or clammy
  • Palpitations
  • Dizziness
  • Subjective confusion or disorientation
• Symptoms that reflect a specific infective source include:

  • Chest source: shortness of breath, cough, chest pain, sore throat.
  • Urine source: dysuria, increased frequency, urgency or any other lower urinary tract symptoms.
  • Skin source: rashes, blisters, pain.
  • Gastrointestinal source: diarrhoea, nausea, vomiting, rectal bleeding, abdominal pain, sore mouth (due to mucositis).
  • Indwelling line source: pain around the line or rigors after use of the line.
• General clinical findings in neutropenic sepsis may include:

  • Haemodynamic instability (e.g. hypotension, tachycardia, tachypnoea, hypoxia)
  • Fever
  • Reduced urine output
  • Altered conscious level or confusion
  • Mottled/ashen appearance
• The clinical presentation of neutropenic sepsis is similar to sepsis without neutropenia. Whilst initial management does not depend on the actual neutrophil count, it is critical to establish whether a patient is neutropenic to guide ongoing management and to inform prognosis.
• Most cases of neutropenic sepsis are caused by an underlying bacterial infection, but it is important to consider viral and fungal infections.
• Bedside investigations:

  • Urinalysis: to look for urinary tract infection.
  • ECG: should be performed in all acutely unwell patients.
  • Capillary blood glucose: to exclude hypoglycaemia.
• Lab investigations:

  • FBC, U&E, coagulation, CRP, LFTs: white cells low and CRP may also be raised.
  • Serum lactate: sepsis six care bundle.
  • Group and save
  • Blood cultures: at least two sets from a peripheral vein plus a set from an indwelling line if present to look for a causative organism.
  • Arterial blood gas: to assess the extent and severity of any respiratory failure.
  • Microbiological cultures: wounds, urine, stool, sputum, and line tip (if indwelling line infection suspected).
  • Viral respiratory swab: if viral respiratory infection suspected.
• Imaging:

  • Chest X-ray: to look for evidence of pneumonia.
  • High-resolution chest CT: if fungal pneumonia is suspected.
  • Abdominal ultrasound or CT abdomen: if biliary or abdominal infection suspected
• Management:

  • Empirical antibiotic therapy without one hour of arrival at hospital
  • Sepsis six bundle
• First line antibiotic therapy is usually IV piperacillin with tazobactam. Some guidelines may also recommend gentamicin.
• Specimens for microbiological culture should ideally be taken before commencing antibiotic therapy however this should not delay treatment.
• Recombinant granulocyte-colony stimulation factor (G-CSF)

  • Can be used for prophylaxis and treatment of neutropenia
  • Reduce the risk of neutropenic sepsis
  • Stimulates the bone marrow the produce neutrophils
  • E.g. filgrastim
• Complications:

  • Single or multi-organ failure (e.g. renal failure, heart failure and acute respiratory distress syndrome)
  • Venous thromboembolism (e.g. pulmonary embolism)
  • Disseminated intravascular coagulation
  • Opportunistic or hospital-acquired infections
  • Delirium
  • Psychological complications (e.g. anxiety regarding future infections and chemotherapy treatment)
  • Delays in chemotherapy leading to worse cancer outcomes