Febrile Neutropenia
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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.

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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) currently works as a GP Registrar and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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