Antimicrobial resistance

Question 1

How can antibiotics be classified?

Answer 1

• Bactericidal or bacteriostatic (kill or stop replication?)
• spectrum (broad or narrow?)
• target site (cell wall, protein synthesis or folate)
• chemical structure/class e.g. B lactams

Question 2

How to chose an effective antibiotic?

Answer 2

• Is it active against target organism ?
• can it reach the site of infection?
• can it be administered in the right formulation (IV or oral - IV is hard at home)
• half life - dosing ?
• interactions with other drugs?
• toxicity?
• need to be monitored?
• allergies?

Question 3

What are the 3 ways to measure antiboitic activity ?

how long do they all take?

Answer 3

1. Disc sensitivity testing - antibiotic disc creates a diameter that s microbe free on agar plate - the bigger the diameter the better the action - diameter = zone of clearance
2. Minimum Inhibitory Concentration (MIC) – Broth Microdilution
   Small tubes filled with antibiotic and microbe, each tube has an increasing conc of antibiotic. If the tube is cloudy the microbe is still present and if clear = antibiotic at that conc has worked
3. MIC – Epsilometer test (E-test) - a strip placed on agar with microbe. The strip is in sections with increasing levels of concentration. Where the area of microbe starts to clear around strip = MIC

they all take at least 24h

Question 4

What is EUCAST?

Answer 4

European Commitiee on Antimicrobial Susceptibility Testing

provides criteria and breakpoints to define if microbes are resistant or not

Question 5

What are the 3 types of antimicrobial resistance?

Answer 5

1. Intrinsic
2. acquired
3. adaptive

Question 6

What is integral antimicrobial resistance?

example

Answer 6

When the microbe doesn’t contain the target/access of the antimicrobial

permanent

e.g. gram negative microbes are NATURALLY resistant to antimicrobial that target the peptidoglycan cell wall

Question 7

What is acquired antimicrobial resistance?

example

Answer 7

It is caused by a mutation

permanent

e.g. influenza and malaria have become resistant to many treatments due to gene transfer to mutation

Question 8

What is adaptive antimicrobial resistance?

example

Answer 8

When the microbe response to stress from subinhibitory levels of antimicrobials

e.g. subinhibitory levels can cause bacteria to turn on genes that help the be resistant

Question 9

What are the 3 mechanisms to resistance?

Answer 9

1. Enzymatic modification of antimicrobial
2. enzymaitc alteration of targets
3. Over expression of effluent pumps

Question 10

Decribe how enzymatic modification of antimicrobials leads to resistance

Answer 10

Some antimicrobials have developed enzymes that act in antimicrobials entering the microbe rendering them useless

e.g. beta lactamase, an enzyme produced by Staphylococcus aureus, inactivates ß-lactam antibiotics

Question 11

Descibe how enzymatic alteration of antimicrobial target leads to resistance.

Answer 11

Alter the shape of target that the antimicrobial binds to and acts upon - this means there is now no site for the antimicrobial to act or bind = no effect

Question 12

Describe how over expression of efflux pumps leads to resistance.

What type of resistance is common here?

Answer 12

These pumps are used to pump the antimicrobial out of the microbe

over expression means the antimicrobial cannot rise to a high enough level in the microbe to kill

this causes broard spectrum resistance

Question 13

How does a resistance trait/gene spread through the microb population ?

Answer 13

1. Reproduction - the microbe with the mutation survives and passes on the beneficial gene
2. horizontal gene transfer (very common in bacteria) - pillus develops and allows the transfer of DNA from plasmids containing mutation - donation - they can now both donate and repilcate