Overview
Neutropenic sepsis
Neutropenic sepsis is a life-threatening complication of cancer and immunosuppressant drug treatment defined as a temperature >38°C or signs/symptoms of sepsis in a person with an absolute neutrophil count of 0.5×109 /L or lower.
Febrile neutropenia
The definition of febrile neutropenia varies but can be described as an oral temperature >38.3°C or two consecutive readings of >38°C for 2 hours along with an absolute neutrophil count of 0.5×109 /L or lower.
Causes
Causes of infection
Infection can occur via breaks in the skin or mucosal surfaces, which may also be worsened due to chemotherapy and radiotherapy (e.g. mucositis). Pathogens can also enter via indwelling catheters.
Coagulase-negative and Gram-positive bacteria are the most common cause, including Staphylococcus epidermidis, possibly due to the use of indwelling lines.
Other infective agents can include viruses and fungi, and host endogenous flora can be the primary source of infection. Candida and Aspergillus species are common causes of fungal infection in neutropenic people.
Causes of Neutropenia
Neutrophils are part of the first-line defence in the inflammatory response. Causes of neutropenia include:
- Cytotoxic chemotherapy – a common cause, can induce myelosuppression
- Radiotherapy – can damage myeloid stem cells
- Immunosuppressive drugs – including disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, azathioprine, and sulfasalazine
- Other drugs – including carbimazole, phenytoin, valproic acid, clozapine, olanzapine, allopurinol, NSAIDs, and penicillin
- Haematological malignancy – can cause bone marrow crowding, abnormal neutrophil function, and hypogammaglobulinaemia
- Autoimmune disease – rheumatoid arthritis, systemic lupus erythematosus, and Crohn’s disease can cause neutrophil destruction themselves
- Viral infections – can cause transient bone marrow suppression and neutropenia, such as HIV, hepatitis B, cytomegalovirus, the Epstein-Barr virus, influenza, and respiratory syncytial virus
Epidemiology
- Incidence in the UK varies from 3 cases per month in general hospitals to >20 per month in specialist oncology units
- The European Society for Medical Oncology (ESMO) states that febrile neutropenia can occur in around 8 per 1000 people receiving cancer chemotherapy
Risk Factors
- Causes mentioned above
- Age: infants and people >60 years old
- Corticosteroids – due to additional immunosuppression
- Antibiotics – as they can disrupt the normal body flora
- Advanced malignancy
- Prolonged hospital admission
- Comorbidities including diabetes mellitus, liver disease, renal disease, poor nutrition
Investigations
Overview
Antibiotics should be started immediately if neutropenic sepsis is suspected, do not wait for the white cell count. Investigations can look to help identify underlying causes:
- Blood cultures: ideally performed before antibiotics but this should not delay giving them, identifies causative organism
- Full blood count (FBC): shows neutropenia
- Urea and electrolytes (U&Es): may show renal dysfunction, which could suggest acute kidney injury due to sepsis or chemotherapy
- Liver function tests (LFTs): may be deranged due to infection or drug toxicity
- Chest X-ray: if cough, abnormal breath sounds etc. are present
Management
Antibiotics should be started immediately if neutropenic sepsis is suspected, do not wait for the white cell count:
- 1st-line: piperacillin with tazobactam (Tazocin)
- If unsuccessful, other antibiotics including meropenem and vancomycin may be used
Once neutropenic sepsis is confirmed, the patient is risk assessed to see if they can be managed as an outpatient.
If it is anticipated that people are likely to have a neutrophil count <0.5 x109/L due to treatment, they should be given fluoroquinolone prophylaxis.
Prognosis
- Mortality rates in adults have been reported to range from 2-21%
