Neutropenic Sepsis

Question 1

What is cancer?

Answer 1

rapid proliferation of a cell in the body
- uncontrolled cell growth

Question 2

How is cancer treated?
intent vs timing

Answer 2

intent
- palliative = control symptoms/prolong life
- curative = cure the cancer

timing
- neo-adjuvant = before the surgery to downsize the tumour, increasing surgical access
- adjuvant = after the surgery to remove micro-metastases and reduce risk of recurrence

Question 3

What is cytotoxic chemotherapy? What cells can be targeted and what is their side effects?

Answer 3

cytotoxic chemotherapy
- medicine that act by targeting rapidly dividing cells
= are preferentially targeted over other slower dividing cells in the body

other cells can be affected and have toxicities
- blood cells (RBCs/WBCs/Platelets) = anaemia, neutropenia, thrombocytopenia
- hair cells = alopecia
- mucous membranes = ulceration
- germinal cells = can reduce fertility

Question 4

How is chemotherapy given? What is an example?

Answer 4

chemotherapy is given in cycles
- treatment period followed by recovery then another treatment period

usually 2-4 weekly depending on regimen

FEC
- fluorouracil, epirubicin, cyclophosphamide

Question 5

What is the difference between solid tumours and haematological cancers?

Answer 5

solid tumours
- rarely affect blood counts unless bone marrow is involved
- have temporary decreases in blood count due to treatment

haematological malignancies
- affect blood counts
- already have low blood counts prior to treatment
= leukaemia, lymphoma, myeloma

Question 6

What is neutropenic nadir? When does it occur?

Answer 6

neutropenia occurs after chemotherapy is given
- neutrophil levels reach a low point 7-10 days after treatment
- <0.5 x10^9 /L

neutropenic nadir is when neutrophils reach the ‘lowest point’
- at this point there is the highest risk of infection

once the count is recovered, then the next cycle of chemotherapy treatment can be given

Question 7

What are the symptoms of neutropenic sepsis? When do they occur?

Answer 7

symptoms
- fever
= signs and symptoms may be reduced due to lack of an inflammatory reaction

risk of infection is great with a decline in neutrophil count and longer duration of neutropenia (>7 days)

occurs when neutrophil count is <0.5 x10^9 /L

Question 8

What are the causative pathogens of neutropenic sepsis?

Answer 8

gram positive
- streptococcus
- staphylococcus

gram negative
- E.coli
- klebsiella spp
- pseudomonas aeruginoda

fungal
- candida
- aspergillus

Question 9

What are the risk factors for neutropenic sepsis?

Answer 9

age >65 years
advanced disease
previous chemotherapy or radiotherapy
open wounds surgery
poor nutritional status
poor renal function
liver dysfunction
cardiovascular disease
HIV infection

Question 10

What investigations can be done for neutropenic sepsis?

Answer 10

physical
- temperature, pulse, blood pressure, oxygen saturations, NEWS score

blood test
- full blood count, renal and liver function tests, lactate, CRP

blood cultures
- from line and peripheral vein

site of possible infection

urine sample

chest X-ray

Question 11

What is the treatment for neutropenic sepsis?

Answer 11

first line
- piperacillin/tazobactam 4.5g IV QDS with amikacin 15mg/kg IV stat then adjust to renal function

mild penicillin allergy/high dose methotrexate
- ceftazidime 2g IV TDS with amikacin 15mg/kg IV stat then adjust to renal function

severe penicillin allergy
- teicoplanin 400mg BD 3 doses then OD, ciprofloxacin 400mg IV BD and amikacin 15mg/kg IV stat then adjust to renal function

Question 11

What is the treatment for neutropenic sepsis?

Answer 11

first line
- piperacillin/tazobactam 4.5g IV QDS with amikacin 15mg/kg IV stat then adjust to renal function

mild penicillin allergy/high dose methotrexate
- ceftazidime 2g IV TDS with amikacin 15mg/kg IV stat then adjust to renal function

severe penicillin allergy
- teicoplanin 400mg BD 3 doses then OD, ciprofloxacin 400mg IV BD and amikacin 15mg/kg IV stat then adjust to renal function

Question 12

What antibiotics should be used for neutropenic sepsis with
- MSSA
- MRSA
- Carbapenemase gram negative

Answer 12

MSSA - flucloxacillin
MRSA - vancomycin
Carbapenemase gram negative - colistin IV

Question 13

What prophylactic antibiotics are used gram negative bacteria like pseudomonas aeruginosa?

Answer 13

use fluoroquinolones
- ciprofloxacin 500mg PO BD
- levofloxacin 500mg PO OD

Question 14

What is filgrastim? What is it used for? When is it given?

Answer 14

contain recombinant G-CSF to stimulate the bone marrow to produce white blood cells
- used to prevent neutropenia in susceptible patients
= G-CSF is a type of growth factor that makes the bone marrow produce more white blood cells

given over or before the expected nadir period
- usually 5-9 days

5mcg/kg SC OD
- <80kg = 300mcg
- >80kg = 480mcg

Question 15

What is haematopoiesis?

Answer 15

process by which the body produces blood cells and blood plasma
- erythrocytes, platelets, granulocytes, lymphocytes, and monocyte
= starts with a pluripotent stem cell

Question 16

What is the main side effects of filgrastim? How is it managed?

What are precautions associated with filgrastim?

Answer 16

bone pain
- managed with paracetamol with/without NSAIDs

precautions
- pulmonary adverse effects
= cough, fever, dyspnoea

• capillary leak syndrome
  = dyspnoea, hypoalbuminaemia, oedema, haemoconcentration (rise in RBCs)
• glomerulonephritis

Question 17

When should filgrastim be used?

Answer 17

if the risk of febrile neutropenia from chemotherapy regimen is 20%
- if 10-20% then consider patient risk factors before use

Question 18

How should low platelet and erythrocyte count caused by chemotherapy be treated?

Answer 18

platelets
- rarely required unless platelet count is <20
- usually delay chemotherapy by a week and consider dose reduction

erythrocytes
- give blood to raise haemoglobin quickly