Lecture 20 - Antimicrobial Drug Resistance Flashcards

1
Q

When was the first case of penicillin resistant S aureus?

A

1947

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2
Q

When was the first case of MRSA in the UK?

A

1960

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3
Q

What are the two types of resistance?

A

intrinsic and acquired

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4
Q

What is intrinsic resistance?

A

if we give a antibiotic used for gram positives to treat gram negatives

e.g. gram negatives are intrinsically resistant to vancomycin

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5
Q

How is acquired resistance acquired?

A

either by vertical or horizontal transfer

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6
Q

What is vertical transfer?

A

if a mother cell is in the presence of a drug, it is possible that some spontaneous mutations occur leading to this sensitive cell producing some drug resistance

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7
Q

What can drug resistant bacteria do?

A

survive and multiply and form many colonies of bacterial cells carrying DNA that will code for drug resistance

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8
Q

What are the steps of vertical transfer?

A

non resistant bacteria exist

bacteria multiply by the millions

some mutations make the bacterium drug resistant, in the present of drugs only the resistant bacteria survive

drug resistant bacteria multiply and thrive

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9
Q

What are the types of horizontal transfer?

A

transformation

conjugation

transduction

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10
Q

What is transformation?

A

if a drug resistant cell is killed by another antibiotic, the bit of the plasmic with genes conferring drug resistance can be transferred to another cell

bacterial cell transferring info to another bacterial cell

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11
Q

What is conjugation?

A

when bacteria are in close proximity and can transfer genes coding for drug resistance from a resistant bacterial cell by producing a bridge/link between the two cells

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12
Q

What is transduction?

A

happens when a bacterium becomes infected with a virus

viruses replicate inside the bacterial cell and if they do this within a drug resistant bacteria then once they leave they take some DNA coding for drug resistance

they continue to reinfect sensitive bacterial cells and bring these bits of info coding for resistant into these cells

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13
Q

What are bacterialphages?

A

viruses that infect bacteria

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14
Q

Examples of antimicrobial resistance?

A

reducing drug accumulation

inactivating/altering drugs

altering target sites

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15
Q

Reducing drug accumulation?

A

production of efflux pumps which remove any antibiotics that enter the cell

changes the structure of the porins

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16
Q

What does changing the structure of the porins do?

A

they no longer act as a way for small hydrophilic drug molecules to get into the gram negative - stops the drug working

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17
Q

Inactivating/altering drugs?

A

beta lactamases

degrade beta lactam antibiotics

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18
Q

What can the resistance genes of beta lactamases code for?

A

new penicillin binding proteins that work in the presence of beta lactams

19
Q

Altering target sites?

A

changes in ribosomes (macrolides)

changes in PBPs (MRSA)

20
Q

What is there correlation between with AMR?

A

antimicrobial resistance/overuse and high levels of AMR

21
Q

What do resistant microbes do?

A

increase the severity and duration of an illness (high costs)

22
Q

Why is rapid emergence of AMR a problem?

A

ease of transfer between species

bacteria multiply very rapidly and are able to transfer the genes coding for drug resistance very easily

23
Q

What is a reason AMR is such a problem?

A

dramatic decline in antibiotic research and discovery

24
Q

What are the ESKAPE pathogens?

A

Enterococcus faecium

S. aureus

Klebsiella (-ve)

Acinetobacter (-ve)

Ps. aeruginosa (-ve)

Enterobacter

25
Q

Why are the ESKAPE pathogens a problem?

A

they have developed ways to resist most of the current drugs available

need to find alternative ways to treat these

26
Q

What are beta lactamases?

A

bacterial enzymes that degrade beta lactam antibiotics

27
Q

What was penicillinase produced by?

A

first penicillin-resistance S. aureus

28
Q

What % of S. aureus are resistant to benzylpenicillin?

A

> 90%

29
Q

What was developed in response to resistance?

A

meticillin (no longer used by gave flucloxacillin)

temocillin

30
Q

Why is flucloxacillin beta lactamase resistant?

A

it has a bulky side chain which acts as a protective shield to protect the carbon on the beta lactam ring from being attacked by beta lactamases

31
Q

Why is temocillin resistant to beta lactamases?

A

has an additional O methyl substituent which stops the beta lactamases attacking the neighbouring carbonyl

32
Q

Co-amoxiclav?

A

amoxicillin + clavulanic acid

33
Q

Tazocin?

A

piperacillin + tazobactam

34
Q

What are beta lactamase inhibitors?

A

clavulanic acid and tazobactam

35
Q

What were meticillin type drugs developed for?

A

to resist beta lactamase attack

36
Q

What did MRSA do?

A

meticillin resistant staph aureus

found a way to produce new PBP that are not inhibited by flucloxacillin

37
Q

What is the one treatment choice for MRSA?

A

vancomycin

38
Q

What is VRSA?

A

there are now some vancomycin resistant staph aureus so there needs to be new treatments developed

39
Q

What do extended spectrum beta lactamases degrade?

A

penicillins (except temocillin)

cephalosporins

monobactams

40
Q

What do metallo-beta-lactamases (NDM 1) degrade?

A

penicillins

cephalosporins

carbapenems

41
Q

What do metallo-beta lactamase (KPC) degrade?

A

penicillins

cephalosporins

monobactams

carbapenims

42
Q

What are some metallo beta lactamases?

A

not inhibited by clavulanic acid nor tazobactam

43
Q

How to tackle AMR?

A

use antibiotics in the right way

dont keep/share antibiotics

never use antibiotics for viral sore throats

select most appropriate antibiotic

reserve highly effective antibiotics for severe infections

provide advice

develop local antimicrobial guidelines

prevent transmission

develop quicker diagnostics

support drug discovery

develop education/training

raise awareness