Contents
Introduction
Definition: Febrile neutropenia is the presence of a fever > 38oC and with an absolute neutrophil count of <1.0×109/L [1]
Note that in many hospital policies, patients may be considered to have febrile neutropenia if they have a recorded fever and recent (usually within last 2 weeks) chemotherapy, even if the neutrophil count is not (yet) low.
- Neutropenia occurs due to bone marrow suppression
- Patients with neutropenia are less likely to produce an effective immune response to infection
- Bone marrow suppression is common side effect of chemotherapy, but has many other causes (anaemias, genetic defects drugs, infections)
- Patients are at a very high risk of developing life threatening bacterial infections and sepsis
- Infection should always be considered in patients who are systemically unwell, and who are receiving chemotherapy, even though fever may not be present.
Key Points
- Suspect febrile neutropenia in all patients receiving chemotherapy who develop a fever ( >38oC) or patients appear systemically unwell
- ALWAYS ask patients who have recently been diagnosed with cancer if they are receiving chemotherapy, as this information may not always be offered
- In all suspected FN cases, patients should be referred to the hospital (preferably the oncology team) for an urgent FBC, assessment and consideration of immediate antibiotic therapy.
- If FN suspected, DO NOT wait for FBC results, as patient may deteriorate rapidly
- National guidelines state that all patients should receive (IV broad spectrum) antibiotics within 60 minutes. [2]
Signs and Symptoms
Symptoms can be non-specific and can have no localised features.
- Feeling hot/cold
- Rigors
- Sweats
- Flu like symptoms
- General malaise
- Ask about sore mouth or diarrhoea as this is common as chemotherapy
- Mucositis can be an entry route for host flora into the blood stream
Initial Clinical assessment
History
- Patient in high risk group?
- Renal failure
- When was last chemotherapy cycle?
- Any recent blood products
- Any Intravascular devices
- Check past microbiology results for any history of resistant organism
Examinations
- Cardiac and respiratory symptoms
- Pyrexia, stigmata of infective endocarditis, skin rashes, lymphadenopathy
- Potential foci of infection
- ENT examination
- Fundoscopy
- GI tract
- Respiratory system
- Genitourinary tract
- Neurological (e.g. signs of meningism)
Investigations
- FBC (check the neutrophil level!)
- Two blood set cultures from a peripheral vein, and any indwelling venous catheters
- Radiological investigations also can be performed if needed
- Other Investigations
- Blood film , D-dimer and fibrinogen testing
- U+E, creatinine
- LFT
- CRP, ESR
- CXR
- Coagulation screen
- Serology/polymerase chain reaction for virus (e.g. CMV)
- Other specialised investigations include: bronchoscopy and CT scans
Management of febrile neutropenia
- Empiric IV broad spectrum antibiotic therapy, according to the local policy. Should be done before FBC results if patient in shock
- Supportive measures: IV fluids, if necessary
- Colony stimulating factors may be considered in high risk patients, with prolonged (>10 days) or serious neutropenia (<0.1×109/L), hypotension and multi-organ failure
- Oral antibiotics: Only in some low risk FN patients. Haemodynamically stable and also who DO NOT have: pneumonia, acute leukaemia, evidence of organ failure, indwelling venous catheter and severe soft tissue infection
- Quinolone with amoxicillin + Clavulanic acid is the most preferable choice, due to the rise of Gram+ FN episodes.
- Oral quinolone should be avoided in patients who have quinolone antibacterial as prophylaxis
- NICE suggest that all patients requiring IV treatment should be started on a β-lactam monotherapy, with piperacillin and tazobactam
- Aminoglycosides should be AVOIDED for initial empirical therapy, unless specific patient or local related reasons
- Coverage of MRSA or gram negative bacteria may be required. Pneumonia diagnosed, antibiotic cover extended for treatment of atypical organisms. Adding a macrolide antibiotic.
Multinational Association for Supportive Care in Cancer (MASCC) index can be used as a risk assessment tool to assess whether a patient is low or high risk.
References
[1] Naik, JD et al. (2011). Febrile neutropenia. British Medical Journal. 342 (1), 103-104.
[2] Rull,G et al. (2012). Neutropenic Patients and Neutropenic Regimes. Available: http://patient.info/doctor/neutropenic-patients-and-neutropenic-regimes. Last accessed 29/01/2016.