L37 Febrile Neutropenia

Question 1

What is febrile neutropenia.

How does chemotherapy cause neutropenia and how can it contribute to increased risk of febrile neutropenia

Answer 1

Febrile neutropenia is an infection, generally bacterial in neutropenic patient

Neutropenia cause: Chemotherapy for leukaemia

1. disrupts normal haemopoiesis so decrease in
   - RBC, platelet - replaced with transfusion, after end of lifespan.
   - WBC, and Neutrophils especially bc they have lifespan of 1-2 days.
2. damages rapidly growing cells - epithelium of GI tract and mouth providing break in the innate immune protective surface
3. Delivery of chemotherapy through central catheters increases risk of skin bacteria passing through.

Question 2

How does Febrile neutropenic present and why, what increases the risk of infection (neutrophil values)

Answer 2

Nothing in history/examination suggests site of infection
eg. SOB, abdo pain, dysuria

-Temperature >37.5 C, nothing else abnormal
This is because neutrophils cause signs of acute infection (red, hot, swelling, tenderness)

-30% high rate of bacteremia.

Risks increased

• if neutrophils <0.1 x 10^9 /L (greater than 1% risk)
• Prolonged and severe neutropenia: 33% by 1 wk, 100% by 6 wks.

Question 3

What are common types of bacteria causing febrile neutropenia, which causes severe disease and where do they come from

Answer 3

• Gram + cocci: CON Staph, Strep, : not likely to die, does make unwell.
• Aerobic Gram negative bacilli: E-coli, Pseudamonas Aeruginosa (1960) : Bacteremia has very high mortality

These are from endogenous gut or skin flora that have been allowed to proliferate unchecked, cross over into capillaries into the blood

Question 4

What is the treatment and time course for febrile neutropenia - to reduce mortality

Answer 4

1. Within 1 hour of presentation there must be administration of empiric broad spectrum antibiotics :

Tazocin: active against almost all aerobic bacteria

• Piperacillin
• Tazobactam

Gentamicin: active against almost all aerobic gram (-) bacilli.

2. Blood cultures are done to find out the organism and which antibiotics its resistant to.
3. Treatment continued until recovery of neutrophil count with resolution of fever. Change to monotherapy with Tazocin alone.
4. Repeat bone marrow exam day 29 to confirm remission of cancer

Question 5

Does nursing patient in isolation reduce risk of neutropenic fever

Answer 5

NO Being in the haematology ward with HEPA filter reduces fungal, viral transmission but this infection is from endogenous source.
2-3 days reduced fever but no impact on survival. Isolation is difficult for patients and nursing

Question 6

Does giving antibiotic prophylaxis- quinolones reduce risk of neutropenic fever: pros and cons

• antifungal and viral prophylaxis already given

Answer 6

• It does decrease the risk of death compared to no intervention and prevent episode of infection occurring by reducing density of organisms in GI tract and in blood.
• However without neutrophils the killing isn’t as good. This leads to increase to quick colonisation with antibiotic resistant bacteria in gut that can now proliferate easily and cause serious bacteremia
• More likely in haematology ward where antibiotics are used heaps. Possible for contam of the ward with resistant bacteria.

Question 7

Does using haematopoietic growth factors reduce impact of neutropenic fever and is it funded

Answer 7

GCSF, EPO, Filagrastin can be used to reduce the depth and intensity of neutropenia therefore decrease risk of febrile neutropenia.

It is funded as prophylaxis for non-myeloid leukaemia with >20% risk of FN

Question 8

What are other causes of neutropenia

Answer 8

1. Inadequate production of neutrophils or neutrophil adhesion molecules (inherited)
2. Inadequate chemotaxis by neutrophils (Jobs)
3. Inadequate intracellular killing by neutrophils (chronic granulomatous disease)
4. Some body sites lack neutrophils (will get there in 12-24 hours)
   - eg. CSF, Joint fluid