Antimicrobial resistance Flashcards
1
Q
What are antimicrobials?
A
- chemicals that either kill or prevent the growth of microbes (bacteria, viruses, protozoa)
- can be produced by microorganisms themselves/ lab
2
Q
What are the impacts of antibiotic resistance?
A
- health
- welfare
- economics
- superbugs
- reduced spectrum of drugs available to treat infections
- no treatment available?
3
Q
What are the drivers of AMR?
A
- world travel (3 million flights/ get to any place in 48 hours)
- mass treatment of livestock with antibiotics
- bush meat imported (zoonotic bugs)
4
Q
What % of emerging infectious diseases are of animal origin?
A
75%
5
Q
Name examples of prophylactic and metaphylatic uses of antibiotics in animals
A
- after surgery
- dry cow therapy
- before transport
- potential outbreaks
- stressful conditions
- moving calves
6
Q
What is metaphylatic?
A
-treat all animals when only a few are showing clinical signs
7
Q
What are sub-therapeutic antibiotics?
A
- resistance radiates from farms through water supplies etc.
- travel through food chain
8
Q
What is a withdrawal period?
A
-legal time to wait before using any products from the animal that had the antibiotics
9
Q
What is antibiotic resistance?
A
- 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
10
Q
Name other resistance types
A
- disinfections
- heavy metals
- antimicrobials incorporated into plastics
11
Q
How do antibiotics work?
A
- 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
12
Q
Which antibiotics stop cell wall synthesis?
A
- Penicillins
- Cephalosporins
- Carbapenems
- Daptomycin
- Glycopeptides
13
Q
Which stop DNA synthesis?
A
-Fluoroquinolones
14
Q
Which stop RNA synthesis?
A
-Rifampin
15
Q
Which stops protein synthesis?
A
- Macrolides
- Chloramphenicol
- Tetracycline
- Aminoglycosides
- Oxazolidonones
16
Q
Which stops folic acid synthesis?
A
- sulfonamides
- trimethoprim
17
Q
Why has resistance emerged?
A
- 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
18
Q
How can inadequate treatment of infections cause resistance?
A
- 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)
19
Q
Bacterial fitness increased?
A
- 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
20
Q
How is antibiotic resistance acquired? (3)
A
- transformation
- conjugation
- transduction
21
Q
what is transformation?
A
-uptake of free DNA in the environment (the free DNA usually comes from the breakdown of dead bacteria nearby)
22
Q
What is conjugation?
A
-the transfer of plasmids, or small circular pieces of bacterial DNA, containing resistance genes, from 1 bacterium to another
23
Q
What is transduction?
A
- transfer of bacterial DNA via viruses, or bacteriophages, to other closely related bacteria
- bacteriophages are viruses that only infect bacteria
24
Q
What are ESBL’s?
A
- 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
25
When was EBSL's first described?
-1983
26
Why are EBSL's such a problem?
- 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
27
What are the different types of resistance?
- Innate, natural or intrinsic
- Mutational resistance
- Extrachromosomal, chromosomal or acquired resistance (ESBL)
- Phenotypic/ persister state
- Physical mechanisms of resistance e.g. Biolfims, salmonella
28
What are the mechanisms of resistance?
- 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
29
What is the 'Altered target site' mechanism?
- altered ribosomal protein
- altered/ new binding proteins
- ribosomal RNA methylation
- altered DNA gyrase
- insensitive dihydropteroate
- ribosomal protection
- insensitive dihydrofolate
- altered cell wall stem peptide
30
What are the antibiotic destroying mechanisms?
- Aminoglycosides
- Beta-lactamases
- Chloramphenicol
31
What is used by the bacterium to decrease the uptake of the drug?
-Beta-lactamase (alteration in bacterial permeability)
32
What is cross resistance?
- implies that a single mechanism covers resistance to multiple antimicrobial agents
- multiple mechanisms involved
33
What is MAR?
- 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.)
34
What is the MAR locus? (E.Coli/ Salmonella)
- 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
35
What do efflux pumps do?
- 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)
36
What are the types of efflux pumps?
- 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)
37
What does phenotypic resistance allow?
- allows bacteria to survive exposure to antimicrobials
| - grow back when antibiotic pressure is removed
38
What are the possible solutions to phenotypic resistance?
-Mutant prevention concentration (MPC)
39
What is MPC?
-the lowest concentration of antibiotic to inhibit the emergence of mutants
40
What is the persister state?
- 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
41
How are antibiotics administered?
- injection
- topical
- oral
- in feed
- in water
- pulse admin- reduce resistance
42
Alternatives to antibiotics?
- probiotics
- prebiotics
- synbiotics
- phage therapy
- natural plant extracts (oregano)
- breed animals for resistance
- vaccines
- husbandry practises
- education
