7. One health selection and transmission of antimicrobial resistance Flashcards

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1
Q

What is One Health?

A

It is a type of study method that considers humans as animals and part of the environment. The interactions between humans, animals and the environment are studied to determine how these impacts outcomes like resistance in infections.

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2
Q

What are the most likely bacteria to spread between humans and animals and why?

A
  1. Faecal bacteria like enterobacterales.
  2. This is because poo gets everywhere and is hard to decontaminate.
  3. Faecal bacteria also survive well in the environment.
  4. This is mostly through the faecal oral transmission route.
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3
Q

What do other infections need to jump between animals and humans?

A

Lots of contact and interactions between the 2. This mostly effects farmer workers.

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4
Q

What do most Zoonotic bacterial infections in the UK cause?

A

Food poisoning

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5
Q

What are the 2 most common bacteria that cause food poisoning in the UK?

A
  1. Campylobacter
  2. O157:H7 which is a pathogenic E.coli strain
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6
Q

What normally causes the contamination in food poisoning cases?

A
  1. Faecal bacteria from animals or humans contaminate the meat and the meat is undercooked and eaten.
  2. Hand washing is not done properly during preparation of the meat and then the bacteria get ingested.
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7
Q

Where do most campylobacter cases come from?

A

Mostly poultry but sometimes pigs.

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8
Q

Where do most O157:H7 cases come from?

A

Contaminated beef

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9
Q

Where does O157:H7 live?

A

In the rectum of cattle

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10
Q

What are the food poisoning bacteria?

A
  1. Professional pathogens
  2. They have a very low infectious dose of usually <100
  3. Act very quickly
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11
Q

What antibiotic are lots of campylobacter infections resistant to?

A

Ciprofloxacin

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12
Q

Why are lots of campylobacter infections resistant to ciprofloxacin?

A
  1. Ciprofloxacin is a fluoroquinolone
  2. Chickens are often given fluoroquinolones like enrofloxacin.
  3. It is water soluble which makes it easy to give to chickens but also means is spread round the environment easily.
  4. It is given to all chickens as prophylactic treatment and then the sick chicken often cannot get to the water to get treatment.
  5. Fluoroquinolones are very stable in the environment so get into other parts of the farm and even last for when a new flock or new chickens are bought into the same place.
  6. This is bad antimicrobial stewardship and leads to resistance spreading in the environment
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13
Q

What resistance is antibiotic resistant zoonotic infections associated with?

A

resistance to antibiotics/antibiotic classes the animal was given during their life

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14
Q

What is now illegal to prevent fluoroquinolone resistant zoonotic infections?

A

Prophylactic treatment

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15
Q

Do bacteria in the environment and flora cause infections?

A
  1. Yes
  2. They are opportunistic infections of mostly vulnerable patients.
  3. We are exposed to the bacteria all the time so they are mostly commensal.
  4. These bacteria are not very virulent.
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16
Q

What helps prevent O157:H7 food poisoning?

A

The cattle are vaccinated against O157:H7 E.coli.

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17
Q

What are the food testing limits for pathogenic bacteria?

A

Very strict

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18
Q

What are the food testing limits for opportunistic bacteria?

A
  1. A lot more relaxed because any stricter is unrealistic.
  2. For opportunistic E.coli is around 300 bacteria per gram of meat
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19
Q

How do vegetables get contaminated with faecal bacteria?

A

Veg is fertilised with manure. The manure is meant to be processed to kill the bacteria but this often fails.

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20
Q

Who/what was studied as part of HSTAR, the UoB One Health study?

A

The bacteria found in:
1. 43 dairy farms
2. 600 dogs
3. UTIs from 146 GP practices
4. 3 major hospitals
5. A zoo

21
Q

What was done to all the faecal samples from HSTAR?

A

They were sequenced and analysed to identify any resistance genes present.

22
Q

What important resistance mechanisms were found in the dairy farms?

A
  1. ampC production
  2. CTX-M production
  3. These are not present at high levels but enough that the presence is worrying.
23
Q

Why are pre-weaned calves a big melting pot for resistance?

A
  1. Due to dry cow therapy.
  2. This exposes the cows to antibiotics given to their mothers in the colostrum.
  3. The calves have no gut bacteria and are picking them up from the environment.
  4. This exposes the bacteria to antibiotic and means only resistant bacteria can colonise these calves.
  5. This is a breeding ground of resistance.
24
Q

What is cefquinome and why is resistance concerning?

A
  1. Cefquinome is a 4th generation cephalosporin that is used in dry cow therapy and not used in humans.
  2. CTX-M can give resistance to it and this has been found in farms.
  3. It is encoded on a plasmid so it can spread to human infecting bacteria.
  4. This then can limit future treatment of resistant infections that could already be resistant to 4th-generation cephalosporins despite no previous use in humans.
25
Q

What does use of antibiotics on farms cause?

A

High levels of resistance to that type of antibiotic

26
Q

Why is framycetin resistance found alongside cefquinome resistance?

A
  1. They are both used in dry cow therapy.
  2. Both CTX-M and framycetin resistance were found on the same plasmid.
27
Q

What is the plasmid that carries both CTX-M and framycetin resistance?

A

pMOO-32

28
Q

What is framycetin?

A

An aminoglycoside antibiotic.

29
Q

What selects for ampC producers?

A

Use of amoxicillin

30
Q

What selects for fluoroquinolone resistance?

A

Use of fluoroquinolones

31
Q

Why has antibiotic use on farms deceased?

A
  1. Heavy campaigning and blaming farms for high levels of resistance.
  2. To get the assured food standard accreditation, you cannot use critical antibiotics unless under strict conditions for sick animals.
32
Q

Has 3rd generation cephalosporin resistance on farms decreased with the decreased use of cefquinome?

A
  1. Yes
  2. Resistance has been reduced in calves but not adult cattle. This is statistically significant.
  3. This is due to the adults having dry cow therapy before it was banned and it takes time to catch up.
33
Q

Why has ampC mediated resistance not decreased?

A
  1. Amoxicillin is not classed as a critical antibiotic so use wasn’t banned.
  2. Amoxicillin/ clavulanic acid is still used just a slightly lower levels.
  3. This means the levels of ampC production in farms didn’t significantly drop.
34
Q

Has fluoroquinolone resistance fallen in farms?

A
  1. No
  2. Use of them was banned but there was not a significant decrease in fluoroquinolone resistance.
  3. This suggests some other factor is impacting the resistance tends. Like the stability of fluoroquinolones means they could still be present on farms despite them not being used for years.
35
Q

How important is different use in driving antibiotic resistance?

A
  1. Study done in Thailand using a predictive model. Could be different in the UK as there is more separation between people and farming.
  2. If human antibiotic use totally stopped = 95% reduction in resistant infection.
  3. If animal antibiotic use totally stopped = 7% reduction in resistant infection.
  4. This shows that while animal antibiotic use contributes to the problem, it is by no means the biggest factor. What we do in people matters the most.
36
Q

Is there evidence that human infections are coming from farm animals?

A

There is very little evidence that whole infections are coming from farm animals, but there is some evidence that farm-specific resistance genes can cross to human bacteria.

37
Q

How would animals bacteria get across to humans?

A
  1. Most likely due to poultry
  2. We are probably studying the wrong bacteria as human gut bacteria would have been acquired while the patients were very young.
38
Q

What increases the risk of excreting 3rd gen cephalosporin resistant bacteria in hospitalised patients?

A

Patients being given ceftriaxone as part of treatment when they are not there for an infection necessarily needing the treatment.

39
Q

What increases the risk of excreting 3rd gen cephalosporin-resistant bacteria in the community?

A
  1. Purchasing food from a fresh market which is less likely to be tested/regulated.
  2. If the person works with poultry.
  3. This shows an epidemiological link between what people do and what resistance they carry.
40
Q

What is the FASRG database?

A

An index of all found farm animal-specific resistance genes in common bacteria.

41
Q

What are FASRGs?

A

farm animal-specific resistance genes.

42
Q

Can FASRGs be found in human infections?

A

Yes, but at a lower percentage then in animals

43
Q

What do FASRGs give resistance to?

A

To antibiotics that are not used to humans and only used in animals.

44
Q

What do puppies do that makes them more likely to excrete resistant bacteria?

A
  1. Being raw fed/eating raw meat.
  2. Cooking meat kills most of the bacteria.
  3. Puppies are still shaping their gut microbiome.
  4. They are picking up lots of resistant opportunistic bacteria from the meat.
  5. Swimming in dirty rivers also increases this due to sewage in the water both human and animal.
45
Q

How do we know that bacteria the puppies/dogs are carrying is from the raw meat they eat?

A

When examining the resistant genes in the bacteria the dogs excrete they have a very similar percentage of FASRG to the bacteria the farm animals excrete suggesting they are the same bacteria.

46
Q

What E.coli resistant strains are often present in bloodstream infections?

A
  1. Phylogroup A and B1
  2. When sequenced, they had a high proportion of FASRG.
  3. These bacteria are much more likely to have come from farm animals, but it is difficult to prove.
47
Q

What happens to Phylogroup A/B1 E.coli when they enter humans?

A

They become humanised

48
Q

How are Phylogroup A/B1 E.coli humanised in the gut?

A
  1. Most Phylogroup A/B1 E.coli infections are opportunistic and enter through a leaky gut.
  2. For faecal bacteria to cause a UTI they require specific virulence factors.
  3. Bacteria from animals often lack the virulence factors needed to cause a UTI.
  4. Once in the gut then, Phylogroup A/B1 E.coli can pick up plasmids from human bacteria in the gut.
  5. These means virulence factors can spread to the animals bacteria quickly and resistance genes from the animal bacteria can quickly spread to other gut bacteria.
49
Q

How has resistance to colistin shown how dangerous the human-animal E.coli plasmid transmission is?

A
  1. Colistin is a very toxic last resort antibiotic for MDR infections.
  2. It is so toxic that for years it was not allowed for human use but was used in animals instead.
  3. The farm animal-specific resistance genes that have developed to colistin over its use have jumped to human gut bacteria through this mixing and have been humanised.
  4. Due to antibiotic resistance we are now using colistin to treat MDR infections.
  5. Resistance to colistin is already fairly common in people without it being used excessively.