Antimicrobial resistance

Question 1

What are antimicrobials?

Answer 1

• chemicals that either kill or prevent the growth of microbes (bacteria, viruses, protozoa)
• can be produced by microorganisms themselves/ lab

Question 2

What are the impacts of antibiotic resistance?

Answer 2

• health
• welfare
• economics
• superbugs
• reduced spectrum of drugs available to treat infections
• no treatment available?

Question 3

What are the drivers of AMR?

Answer 3

• world travel (3 million flights/ get to any place in 48 hours)
• mass treatment of livestock with antibiotics
• bush meat imported (zoonotic bugs)

Question 4

What % of emerging infectious diseases are of animal origin?

Answer 4

75%

Question 5

Name examples of prophylactic and metaphylatic uses of antibiotics in animals

Answer 5

• after surgery
• dry cow therapy
• before transport
• potential outbreaks
• stressful conditions
• moving calves

Question 6

What is metaphylatic?

Answer 6

-treat all animals when only a few are showing clinical signs

Question 7

What are sub-therapeutic antibiotics?

Answer 7

• resistance radiates from farms through water supplies etc.
• travel through food chain

Question 8

What is a withdrawal period?

Answer 8

-legal time to wait before using any products from the animal that had the antibiotics

Question 9

What is antibiotic resistance?

Answer 9

• bacteria can develop resistance through genetic mutation
• the mutations enable the bacteria to alter the way it interacts with the antibiotic
• may mean the antibiotic is ineffective

Question 10

Name other resistance types

Answer 10

• disinfections
• heavy metals
• antimicrobials incorporated into plastics

Question 11

How do antibiotics work?

Answer 11

• interfere with synthesis of the bacterial cell wall
• prevent bacteria from making chemicals they need to survive
• interfere with the genetic material in a bacterial cell and cause it to stop the bacterial cell dividing

Question 12

Which antibiotics stop cell wall synthesis?

Answer 12

• Penicillins
• Cephalosporins
• Carbapenems
• Daptomycin
• Glycopeptides

Question 13

Which stop DNA synthesis?

Answer 13

-Fluoroquinolones

Question 14

Which stop RNA synthesis?

Answer 14

-Rifampin

Question 15

Which stops protein synthesis?

Answer 15

• Macrolides
• Chloramphenicol
• Tetracycline
• Aminoglycosides
• Oxazolidonones

Question 16

Which stops folic acid synthesis?

Answer 16

• sulfonamides

- trimethoprim

Question 17

Why has resistance emerged?

Answer 17

• over use
• ineffective antibiotics prescribed
• use of antibiotic as growth promoters
• illegal use
• patients not completing courses
• inappropriate use of disinfectants
• evoluntionary pressures
• antimicrobials in environment

Question 18

How can inadequate treatment of infections cause resistance?

Answer 18

• wrong treatment
• wrong initial diagnosis
• treatment course too long/short
• dilution of disinfectant wrong
• exposure time to disinfectant wrong

(persistence of organisms/ DNA in environment)

Question 19

Bacterial fitness increased?

Answer 19

• bacteria become fitter, due to other genes now being associated (can now colonise in the gut and survive more easily)
• can now colonise more effectively and are more resistant

Question 20

How is antibiotic resistance acquired? (3)

Answer 20

• transformation
• conjugation
• transduction

Question 21

what is transformation?

Answer 21

-uptake of free DNA in the environment (the free DNA usually comes from the breakdown of dead bacteria nearby)

Question 22

What is conjugation?

Answer 22

-the transfer of plasmids, or small circular pieces of bacterial DNA, containing resistance genes, from 1 bacterium to another

Question 23

What is transduction?

Answer 23

• transfer of bacterial DNA via viruses, or bacteriophages, to other closely related bacteria
• bacteriophages are viruses that only infect bacteria

Question 24

What are ESBL’s?

Answer 24

• Extended-Spectrum Beta-Lactamases
• enzymes that can be produced by bacteria making them resistant to cephalosporins e.g. cefuroxime
• resistance is either plasmid or chromosomal encoded
• dairy problem

Question 25

When was EBSL's first described?

Answer 25

-1983

Question 26

Why are EBSL's such a problem?

Answer 26

- resistance can be carried on a plasmid - plasmids are highly promiscuous - many subtypes - plasmids may confer a fitness advantage plasmid DNA could survive in the environment -transfer to other organisms

Question 27

What are the different types of resistance?

Answer 27

- Innate, natural or intrinsic - Mutational resistance - Extrachromosomal, chromosomal or acquired resistance (ESBL) - Phenotypic/ persister state - Physical mechanisms of resistance e.g. Biolfims, salmonella

Question 28

What are the mechanisms of resistance?

Answer 28

- Efflux of the antibiotic - Membrane plug formation (protein produced to block uptake of drug) - Ribosomal blockade (protein to stop drug binging to ribosomes) - Enzymatic destruction - Alteration of the drug - Persister state/ phenotypic resistance

Question 29

What is the 'Altered target site' mechanism?

Answer 29

- altered ribosomal protein - altered/ new binding proteins - ribosomal RNA methylation - altered DNA gyrase - insensitive dihydropteroate - ribosomal protection - insensitive dihydrofolate - altered cell wall stem peptide

Question 30

What are the antibiotic destroying mechanisms?

Answer 30

- Aminoglycosides - Beta-lactamases - Chloramphenicol

Question 31

What is used by the bacterium to decrease the uptake of the drug?

Answer 31

-Beta-lactamase (alteration in bacterial permeability)

Question 32

What is cross resistance?

Answer 32

- implies that a single mechanism covers resistance to multiple antimicrobial agents - multiple mechanisms involved

Question 33

What is MAR?

Answer 33

- multiple antimicrobial resistance - group of genes = MAR - chromosomally encoded systems involved in low level resistance of bacteria to different classes of antibiotic (mainly B-lactams, disinfectants, organic solvents etc.)

Question 34

What is the MAR locus? (E.Coli/ Salmonella)

Answer 34

- mediate AMR by up-regulating efflux of some antibiotics, disinfectants and organic solvents - via the AcrAB-TolC efflux pump - and down regulation influx through Outer Membrane Protein F

Question 35

What do efflux pumps do?

Answer 35

- membrane proteins - act as an export for antimicrobials - exclude the antibiotic out of the cell as fast as it can enter =low intracellular concs (insufficient to elicit an effect)

Question 36

What are the types of efflux pumps?

Answer 36

- Primary active transporters- utilise the energy stored in ATP to catalase transport of drug across membrane by ATP hydrolysis - Secondary active transporters - driven by energy stored in ion gradients (generated by respiration) - Phosphotransferase system (PTS)

Question 37

What does phenotypic resistance allow?

Answer 37

- allows bacteria to survive exposure to antimicrobials | - grow back when antibiotic pressure is removed

Question 38

What are the possible solutions to phenotypic resistance?

Answer 38

-Mutant prevention concentration (MPC)

Question 39

What is MPC?

Answer 39

-the lowest concentration of antibiotic to inhibit the emergence of mutants

Question 40

What is the persister state?

Answer 40

- the bacteria have no resistant gene (but is resistant) - due to the metabolism of the bacteria (become dormant) - so 99 will die and 1 will survive - will keep happening - use 2/3 antibiotics at same time

Question 41

How are antibiotics administered?

Answer 41

- injection - topical - oral - in feed - in water - pulse admin- reduce resistance

Question 42

Alternatives to antibiotics?

Answer 42

- probiotics - prebiotics - synbiotics - phage therapy - natural plant extracts (oregano) - breed animals for resistance - vaccines - husbandry practises - education