Molecular Medicine: A Case of Febrile Neutropenia

Question 1

What happens

Answer 1

• Severe anaemia
• Immature Blast cells (you don’t usually see in the peripheral bloodstream)
• Low neutrophils and lymphocytes

Referred o the haematology department and bone marrow examination performed. Showed Acute myeloid leukaemia. Increased cellular, immature cells.

What also do chromosomal ananlysis and molecular analysing.

Chemotherapy doe via a 3 tube SVC for ease of venous access

Question 2

All chemotherapies have a backbone of.

Whats the goal of chemo?

Answer 2

• Anthrocylcine
• Cytosine arabinoside

Goal is to eradicate the underlyin leukaemia. BUT it is also ablative to other rapidly dividing cells so normal haematopoeisis, hair cells etc will also be affected.

Question 3

Chemotherapy has prompt effects on a AML patients marrow and peripheral blood.

but what should we be worried about

Answer 3

• They will clear the blood, as well as all WBC to an immeasurable level. This leads to significant immunodepression and infection(s) during this time are common:
• Patients who call feverish, shivering, with a low WBC count: FEBRILE NEUTROPENIA

Question 4

Patient treated with chemo is febrile neutropenic, but shows no signs of infection. The only sign something is wrong is the High temperature 39.4 degrees

Question 5

What is Febrile Neutropenia?

Why does it often have no clinical symptoms

Answer 5

• Common in severly neutropenic patients
• High rate of Bacteraemia
• infection arise from endogenous gut and skin flora
• Very high mortality in patients with gram negative bacteraemia
• Improved outcome with empiric antibiotic treatment

Paitents who lack neutrophils get severe bacterial infections as they have no bacterial clearance. Neutrophils also tell us where the site of infection is as they set up an inflammatory process in the skin eg; a red, angry leg. But with those who don’t have neutrophils, often then DON’T HAVE THE INDICATIVE CLINICAL SIGNS TO TELL YOU WHERE THE INFECTION IS

Question 6

What is the risk of infection related to the neutrophil count?

Answer 6

Riskrises below 0.5 x 10⁹/L

>1% daily risk of bacteraemia with neutrophil count <0.1 x 10⁹/L

When that low the bone marrow has been severely ablated.
with a bone marrow ablation ~0.5 does not run a very severe risk.

The longer the person has a white cell count <1, by 4 weeks you’re at ~100% chance of getting an infection

Question 7

____% of patients with febrile neutropenia are bacteraemic

Answer 7

30%

Infectioin arise from damaged barriers in the gut and the skin; eg; in the mouth/tongue, or from organisms tracking up the cannuler

Question 8

Organisms the cause febrile neutropenia

What was the mortality rates before and after empiric antibiotics?

Answer 8

Usually skin commensual organisms

• staph aureus
• strepticocci
• aerobic gram -ve
• E.coli
• Klebsiella

Before empiric antibiotics: 91% mortality
After Empiric antibiotics: 31%

Question 9

Whats the standard empiric anitbiotic treatment for febrile neutropenia?

These are used immediately whilst waiting for the blood culture results

Answer 9

Tazocin: active against almost all aerobic bacteria

plus

Gentamicin (aminoglycoside): active against almost all aerobic Gram negative bacilli

Once there is a recovery of neutrophil count with a resolution of fever, start on a monotherapy

THen do bone marrow biopsy a month later

Question 10

E.coli (Gm negative bacili) and Coagulase negative staphylococcus (Gm positive cocci) are sensitive and resistant to what?

Answer 10

E.coli:

• Resistant to: augmentin
• Sensitive to: tazocin, ceftriaxone, gentamicin

Coagulase negative staphylococcus:

• Resistant to flucloxacillin
• Sensitive to vancomycin

Question 11

Patients do another 2-3 rounds of consolidation therapy, what does this mean re neutropenia? what should we be doing?

Answer 11

This is extra high risk of neutropenia.

• isolation? everyward is hepafiltered to take pathogens/spore out of the air to reduce risk. BUT there’s no evidence to prove that isolation will provide any benefit as the pathogens come from skin and gut
• prophylactic antibiotics? significantly reduces mortality risk in comparison to no intervention. BUT the antibiotic resistant endemics that occur can be far more dangerous in regards to not having treatment for bacteraemia!! so in the overall scheme of thing , the best long term outcome is to not do so. if you have a unwell patient, who is neutropenic, even if they don’t have a feverr they probbaly need empiric AB
• Haematopoietic growth factors? frequently used in patient recieving chemo, G-CSF is a important factor, that reduces the impact and effect of neutropenia! routinely given in conjunction with chemo for regualar cancers, BUT NOT AS EFFECTIVE FOR HAEMATOPIETIC CANCERS the evidence is not there
• Consider reducing intensity