Theme 3 Lecture 21: Antibacterial concepts and antibiotic stewardship

Question 1

How do we test how susceptible a bacteria is to an antibiotic?

Answer 1

we determine the minimum amount of antibiotic that stops the bacteria from growing (the MIC)

Question 2

When experimenting with bacteria to work out MIC, what must be controlled?

Answer 2

• standard amount of culture media

- standard bacterial inoculum / same amount of bacteria so they all grow at the same rate

Question 3

When experimenting with bacteria to work out MIC, what is the independant variable?

Answer 3

antibiotic concentration

Question 4

How do you work out the MIC of an antibiotic?

Answer 4

• Put a standard amount of culture media and same amount of bacteria so they should all grow at the same rate
• But the amount of antibiotic in the test tube is varied
• The bacteria grow and turn the growth media turbid (cloudy)
• As you go to the right, the antibiotic starts to inhibit the growth of the bacteria (so the testubes become clearer as you move to the right)

Question 5

How do we know when the amount of antibiotic administered has reached the point of optimal survival for the patient?

Answer 5

when the amount of antibiotic in the blood > the MIC

Question 6

How can there be intra-species variations in MIC values?

Answer 6

some resistant strains can have higher MIC values

Question 7

What is meant by pharmodynamic target?

Answer 7

• antibiotic:MIC ratio is optimal
• once this target has been achieved, there is no additional efficacy benefit
• antibiotics are dosed to achieve the target, not to exceed
• we should give enough drug, not more and more drug

Question 8

What is pharmacokinetic variation?

Answer 8

• there is variation between patients in how an antibiotic is distributed in the body and cleared from the body
• MIC and PK values vary
• the PD target is fixed

Question 9

What is the probability of target attainment (PTA)?

Answer 9

Statistical analyses (simulations) can be used to determine the probability that, if treated with a certain antibiotic dose, for a certain infection, a patient will attain the desired pharmacodynamic target

Question 10

What is the relationship between drug clearance of a patient and probability of target attainment?

Answer 10

if the drug clearance of a patient is high, the probability of target attainment will be low so you might have an adverse reaction

Question 11

Compare oral antibiotics vs IV antibiotics

think about absorption, IV access, convenience, cost

Answer 11

Oral antibiotics:

• slower absorption
• antibiotic associated diarrhoea
• requires small bowel for absorption
• no IV access required
• no IV side effects
• self-administration
• cheaper

IV:

• faster/instantaneous absorption
• antibiotic associated diarrhoea
• IV access required
• IV access side effects: thrombophlebitis, thrombosis and infection
• medical staff required for administration
• more expensive

Question 12

Are IV antibiotics better than PO antibiotics?

Answer 12

when the drug has reached the systemic circulation, IV and PO antibiotics can be considered equal

Question 13

What is an example of a negative consequence of administering antibiotics for a long duration?

Answer 13

C.difficile/ diarrhoea

Question 14

When should we start antibiotics?

Answer 14

when the benefits of starting are greater than the disadvantages

Question 15

Give an example of when antibiotics should always be started

Answer 15

sepsis

Question 16

Give an example of when antibiotics should never be started

Answer 16

patients with no evidence of infection e.g autoimmune inflammation

Question 17

What are the advantages to early antibiotic therapy?

Answer 17

• mortality and morbidity benefit
• if clinically stable narrow spectrum antibiotics may be administered and the response assessed
• if clinically stable oral antibiotics may be administered and the response assessed
• prevent infection metastases

Question 18

What are the disadvantages to early antibiotic therapy?

Answer 18

• may reduce the time available to do cultures
• reduced chance of giving targeted therapy
• reduced chance of getting a diagnosis
• may increase the chance of giving the wrong antibiotic, or not enough antibiotic
• insufficient time to check allergies

Question 19

What are 4 strategies that can be used when starting antibiotics?

Answer 19

• start early, look to stop/ de-escalate early
• delay antibiotics e.g delayed prescription
• start broad, look to narrow
• start narrow, have a plan of how/when to broaden

Question 20

What is TDM and when is it used?

Answer 20

• therapeutic drug monitoring
• used for vancomycin/teicoplanin and gentamicin
• ototoxic and nephrotoxic drugs

Question 21

What is antibiotic stewardship?

Answer 21

• involves timely and optimal selection of dose and duration of an antimicrobial
• for the best clinical outcome for treatment or prevention of infection
• with minimal toxicity to the patient
• and minimal impact on resistance and ecological adverse events such as C.difficile

Question 22

What % of people report a penicillin allergy?

Answer 22

10%

Question 23

What are the 3 classes of beta lactams?

Answer 23

1. penicillins
2. cephalosporins
3. carbapenems

Question 24

What are the limitations of antibiotics?

Answer 24

• antibiotics will not treat non-infectious diseases
• antibiotics will not treat contaminated samples
• antibiotics may only support infections because they could require surgical intervention
• all antibiotics “damage” your microbiome