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Microbiology > Antimicrobial resistance > Flashcards

Antimicrobial resistance Flashcards

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1
Q

What is an inherently resistant antibiotic?

A

When the antibiotic lacks a a pathway or a target which a drug interacts with, or the drug can’t gain access to the target

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2
Q

What is acquired resistance?

A

This is where a drug which was previously sensitive to an antibiotic has gained some genetic material encoding for resistance

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3
Q

Give some examples of inherent resistance.

A

Vancomycin against gram negative bacteria
- these aren’t taken up by the bacteria and so can’t act on the cell wall
Metronidazole against aerobic bacteria
- This is activated when anaerobically reduced to its active form

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4
Q

List the four ways in which bacteria can develop resistance to antibiotics.

A

Produce enzymes that inactivate or modify antimicrobials
Change the shape of the drug target
Decrease permeability of the cell to the drug
Bacteria are able to export the drug from inside the cell

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5
Q

Give an example of the enzymes that inactivate or modify antibiotics.

A

Beta-lactasmases - inactive beta-lactam drugs

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6
Q

Give an example of target modification in antibiotic resistance.

A

Methylation of the 23S ribosomal subunit, resulting in resistance to erythromycin

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7
Q

Give an example of a bacteria decreasing the permeability of the cell to reduce the amount of antibiotic that concentrates within the cell.

A

Porins which permit drug to pass into a cell can be downregulated - so the concentration required for the drug to be effective increases

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8
Q

Describe the method of antibiotic resistance where the bacteria are able to export the drug from inside the cell.

A

The production of multi-drug resistance efflux pumps.

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9
Q

Give an example of a bacteria that are able to export the drug from inside the cell.

A

Pseudomonas can produce mulit-drug reistance efflux pumps

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10
Q

What are the four main ways bacterial cells can become resistant to antibiotics?

A

Chromosomal mutation
Acquisition of a mobile piece of DNA such as a plasmid, integron or transposon
DNA uptake occurring through transformation
Pieces of DNA being transferred between bacteria and viruses

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11
Q

Why is antibiotic resistance higher in hospitals?

A

There is a selective pressure for mobile pieces of DNA (which carry resistance) to survive

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12
Q

What is vertical gene transfer?

A

Genetic information passed from parent cell to progeny via binary fission

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13
Q

What is horizontal gene transfer?

A

Genes transferred other than through traditional reproduction
- primary reason for antibiotic resistance

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14
Q

How often do resistance mutations occur?

A

Every 10-8 or 10-9 bacteria exposed to a drug

- this is significant given the high replication rate of bacteria

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15
Q

Which causes mutations faster? Spontaneous mutation or acquisition of mobile pieces of DNA?

A

Acquisition of mobile pieces of DNA

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16
Q

Give two reasons why treatment of some infections is done with two different antibiotics.

A

1) If you don’t know the sensitivity of the drug, then this maximises the chance that it will be sensitive to one of them
2) If the bacteria have a mutation that makes it resistant to once drug, the other drug will kill it

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17
Q

Describe conjugation.

A

Requires cell to cell contact between two bacteria
Small pieces of DNA called plasmids are transferred from one cell to another
This is the most important mechanism of horizontal gene transfer

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18
Q

Do the two bacteria involved in conjugation have to be of the same species?

A

No - although conjugation is most commonly seen amongst the gram negatives

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19
Q

What are plasmids?

A

Pieces of circular double stranded DNA

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20
Q

What can the genes within plasmids encode for?

A

Resistance to antibiotics, heavy metals and UV light
Genes which encode pili, mediate adherence and encode toxins
- they also carry genetic information to allow replication and the passage between cells

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21
Q

What factors make plasmids an effective way of spreads resistance?

A
  • multiply in high numbers
  • high rate of cell to cell transfer
  • can be picked up by different species of bacteria
  • they carry resistance to several drugs at once
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22
Q

How does the genetic information in plasmids cause resistance?

A

They relate to enzymes which break down antibiotics or modifications to the membrane drug transport systems

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23
Q

Do plasmids need to use the chromosome of the bacterium to replicate?

A

They are capable of replicating themselves independently of the bacterial chromosome, but they can become integrated within the chromosome

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24
Q

What is transduction?

A

Where small pieces of DNA are transferred between bacteria by a virus

25
Q

What is the name of the virus that infect bacteria, and transduce DNA?

A

Bacteriophage

26
Q

Does the transduction method of gene transfer require same cell transfer?

A

Yes - although the cells don’t need to touch, they are still mainly of the same species

27
Q

What is transformation - in regards to gene transfer?

A

When bacteria die, some naked DNA is released into the surrounding environment
Some (not all) bacteria can take this DNA up and insert it into their own chromosome

28
Q

What happens if, during transformation, the naked DNA is inserted into a region that codes for a penicillin binding protein?

A

There is a change in the penicillin binding protein
- this means it can still cross link the peptidoglycan precursors to form the cell wall, but has a reduced affinity for beta-lactam antibiotics (Such as penicillin)

29
Q

Name the mechanism by which some strains of strep pneuomniae have become resistant to penicillin.

A

Transformation - insertion of naked DNA into the region which encodes for PBP in the bacterial chromosome
- has occurred through acquisition of gens from naturally penicillin resistant Strep species.

30
Q

What is the ‘fitness cost’ in resistant bacteria?

A

Antibiotics attack important biological functions in a cell. Mutations to avoid these antibiotics can result in changes to the normal functioning of the bacterial cell
- which may result in a reduced growth rate (fitness cost)

31
Q

How does ‘selection pressure’ encourage antibiotic resistance?

A

In an environment with heavy antibiotic use (hospital) the benefit of resistance outweighs the drawback of slightly slower growth

32
Q

How are selection pressure and fitness cost related?

A

Bacteria have to try and mutate in a way that doesn’t slow growth - but they sometimes have to if they exist in an environment with high antibiotic use

33
Q

Describe the bacterial changes seen in vancomycin intermediate strains.

A

Increased thickness of the cell wall
Increased number of D-ala-D-ala target that MRSA binds with - which may be preventing the diffusion of the drug deeper into the cell wall

34
Q

Describe the bacterial changes seen in Vancomycin resistance bacteria

A

The strain has picked up the VanA gene from enterococci and they have changed the Vancomycin binding site so that Vancomycin can no longer bind

35
Q

What is the function of normal penicillin binding protein?

A

These mediate the cross linking in the peptidoglycan, which makes up the bacteria cell wall

36
Q

How is MRSA resistant the Methicillin (and all other beta-lactams)?

A

MRSA contains a MecA gene on it’s bacterial chromosome which encodes a variant of the normal penicillin binding protein, with a lower affinity for methicillin.
This decreased affinity allows the bacteria to continue to produce cell wall even in high concentrations of the drug

37
Q

What antibiotic would you give to treat cellulitis?

A

Flucloxicillin

38
Q

When would you consider doing a MRSA screen on a patient?

A

When they come from a nursing home with an infection

- nursing homes are major risk factors for MRSA

39
Q

How do you take a sample for a MRSA screen?

A

MRSA likes to live in moist areas of the body, so a swap will probably be taken from the nose and perineum

40
Q

What are coliforms (And give some examples)?

A

Coliforms are a group of bacteria which live in the gut in humans and animals.
Examples include E.Coli, Klebsiella and enterobacter species

41
Q

Which infections do coliforms commonly cause?

A

Urinary Tract Infections, intra-abdominal sepsis and hospital acquired pneumonia

42
Q

What are the antibiotics commonly used to treat coliform infections?

A

Amoxicillin
Ciprofloxacin (a quinolone)
Cephalosporins
Gentamicin (an aminoglycoside)

43
Q

What is the most common form of resistance in coliforms?

A

Beta-lactamase activity

44
Q

What are extended spectrum beta-lactamases?

A

Enzymes that can hydrolyse the bet-lactam ring of both penicillins and cephalosporins.
- Usually plasmid encoded

45
Q

How are extended spectrum beta-lactamases treated?

A

Ciprofloxacin
Temocillin
Gentamicin
- Meropenem - BEST

46
Q

What is the name of the group of enzymes which are capable of hydrolysing meropenem?

A

Carbapenemases

One of the organisms which carries these enzymes is called NDM-1

47
Q

Name the three methods of carbapenem resistance (meropenem).

A

Porin loss
Increased production of a type of betalactamase enzyme known as AmpC
Carbapenemase enzymes

48
Q

Why are carbapenemase enzymes the most likely to cause high level carbapenem resistance?

A

This is the only mechanism that can spread easily via plasmids

49
Q

Name two carbapenem sparing agents.

A

Gentamicin and Temocillin

50
Q

Name three non-genetic mechanisms of resistance.

A

Protected environment
Resting stage
Presence of a foreign body

51
Q

How can a protected environment within the body cause antibiotic resistance?

A

When the body detects an infection it attempts to isolate it in one area (i.e. an abscess).
This inadvertently protects the bacteria from any antibiotics that may be administered.
In this situation surgery is the best cure

52
Q

Describe the ‘resting stage’ mechanism of bacterial resistance.

A

Bacteria which aren’t dividing are less susceptible to cell wall inhibiting agents (e.g. penicillins and cephalosporins) than rapidly dividing organisms.
- a problem in TB and slow growing dormat tubercule bacilli

53
Q

Describe how the presence of a foreign body can lead to bacterial resistance.

A

1) A foreign body disrupts the immune system

2) Biofilm formation

54
Q

Where are biofilms commonly found in patients?

A

On the surfaces of prosthetic material such as indwelling lines and prosthetic joints

55
Q

Describe what a biofilm is.

A

A highly organised and complex bacterial community with channels for diffusion of water, oxygen and nutrients.

56
Q

What are the three ways in which biofilms can lead to reistance?

A

1) Close proximity of bacteria facilitates gene exchange
2) Channels for diffusion of nutrients are sometimes to small for antibiotics to penetrate
3) Nutrients penetrate in fewer amounts at the bottom of the biofilm, so the bacteria replicate slower and they are ess susceptible to cell wall agents

57
Q

How would you prevent spread of resistance?

A

Use narrow spectrum antibiotics when you can
Follow the empirical prescribing guidance
Short courses (e.g. 3 days for UTI)
Infection control - hand washing, gloves and gowns

58
Q

How are pseudomonas aeruginosa bacteria resistant?

A

They have multidrug efflux pumps - increase drug exit

- this bacteria also turns the patient green

Microbiology (21 decks)

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