Febrile Neutropenia

Original article by Khaleel Loonat | Last updated on 8/2/2016
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Definition: The presence of a fever > 38oC and with an absolute neutrophil count of <1.0x109/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 FN 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 

  • 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

 
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.