Febrile neutropaenia

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Febrile neutropaenia (or neutropaenic sepsis) is not a common problem in the palliative care seting although there are times where it is encountered. Occasionally palliative care doctors will admit patients (e.g. for pain control) who have had recent chemotherapy who then subsequently develop a fever whilst an inpatient. Likewise, patients with haematological malignancies and a long-term neutropaenia may be under the care of a pallaitive care team when a fever develops. How aggressively to treat febrile neutropaenia and whether or not treatment should occur within a palliative inpatient unit will vary from patient to patient and unit to unit and as always in palliative medicine, a one-size doesn't fit all approach is needed. Neutropaenic sepsis can be especially dangerous because patients are unable to mount an adequate immune response to infection. When treatment is appropriate, blood cultures should be taken and broad-spectum empirical antibiotics commenced urgently (within minutes, not hours).

See also: Sepsis

Pathogenesis and epidemiology

Various mechanisms are in action that increase the risk of sepsis in patients with malignancy and chemotherap, in particular:

  • The break down of the mucosal barriers in the mouth and gastrointestinal tract allowing for bacteria to invade more easily
  • The weakened immune system due to the reduced neutrophil count
    • Hhaematological malignancies are particularly high risk conditions for neutropaenic sepsis and death due to the pre-existing problems with the immune system through associated lymphocyte and neutrophil defects

In over two-thirds of cases of patients with febrile neutropaenia no organism is identified. Of those patients who do grow an organism, in most cases, it is probably an organism that is part of the patient's endogenous floral that has breached an area of damaged mucosa. The most commonly grown organisms in cultures are gram positive cocci associated with IV lines. Gram negative rods are also relatively commonly grown. The following lists some of the more commonly grown organisms:

Clinical features

Patients who have had recent chemotherapy often feel tired and fatigued. With the subsequent development of fever this often worsens and there may be signs of a focus of infection. In any patient with recent chemotherapy who feels generally unwell, checking the temperature is key, and, if it is greater than 38.0 then the assumption of febrile neutropaenia should be made.

Neutropaenic sepsis should also be considered as a possible diagnosis when fever is absent but there are other signs of a developing systemic inflammatory response syndrome such as tachycardia or hypotension.

If neutropaenic sepsis is suspected, history and examination focussing on site of infection should be undertaken as this will guide investigations and empiric choice of antibiotics. For example, the presence of erythema and tenderness around an IV line would suggest a possible skin source and suggest that vancomycin should be added to the standard regime of antibiotics to cover Gram positives including MRSA.

Investigations and management

Confirmation of significant neutropaenic requires a blood test confirming a neutrophil count of < 0.5. Treatment should not be delayed whilst awaiting confirmation of this.

Initial investigations of value include

  • Blood culture
  • Other cultures as appropriate - urine, sputum, stool
  • CRP
  • Full blood count
  • Renal function and electrolytes
  • Liver enzymes

Initial management should centre around rapid antibiotic administration (ideally within minutes of the fever developing, not hours). Antibiotics should be directed against a wide range of organisms, particularly Gram positive cocci and Gram negative rods including Pseudomonas aeruginosa. Local guidelines vary and should genearlly be followed. An example of appropriate antibiotics is:

Piperacillin/tazobactam 4.5 grams IV 6-hourly

Many centres treat initially with monotherapy as above (or with dual therapy adding an initial dose of gentamicin). If an IV catheter associated infection is suspected, the addition of vancomycin is appropriate. Other reasons to add vancomycin include:

  • Suspected soft tissue or skin infection
  • Suspected pneumonia
  • Hypotension

In addition to IV antibiotics, IV fluids should be considered. In patients who are haemodynamically unstable, an opinion regarding admission into an intensive care unit for inotropic support should be sought.

As with all things in palliative care, aggressive treatment may not be appropriate and the extent of investigations and treatment should be carefully weighed up by the palliative care team and patient and his/her family.

Duration of antibiotic therapy

Where an organism is identified, the patient should receive IV antibiotics for at least the standard time-frame. Where an organism is not identified, antibiotics hsould continue until the neutrophil count is at least above 0.5 and the patient has been afebrile for a reasonable period of time (e.g. two days).

Removal of PICC lines and CVCs

Many patients receiving chemotherapy have a PIC or central line in situ. If the line is thought to be the source of the infection then it should be removed. Cases where this is likely include:

  • Staphylococcus aureus septicaemia
  • Pseudomonas aeriginosa septicaemia
  • Fungaemias
  • Hypotensive patients
  • Any persistent organism in the bloodstream despite appropriate antibiotics > 6 weeks

Prolonged courses of antibiotics are needed for line associated infections (e.g. of two weeks). In patietns where endocarditis, 4 to 6 weeks of IV antibiotics is standard practice.

G-CSF

G-CSF is not routinely given for patients with febrile neutropaenia but it is worth considering using G-CSF for high risk patients (e.g. those with a very low neutrophil count and an expected relatively long duration of neutropaenia).

Prognosis

There is about a 10% mortality associated with neutropaenic sepsis. In palliatve care patients an episode of neutropaenic sepsis shold prompt consideration about whether or not the benefit of further chemotherapy is outweighed by the risk.

Authors

Graham Llewellyn Grove