7. One health selection and transmission of antimicrobial resistance

Question 1

What is One Health?

Answer 1

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.

Question 2

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

Answer 2

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.

Question 3

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

Answer 3

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

Question 4

What do most Zoonotic bacterial infections in the UK cause?

Answer 4

Food poisoning

Question 5

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

Answer 5

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

Question 6

What normally causes the contamination in food poisoning cases?

Answer 6

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.

Question 7

Where do most campylobacter cases come from?

Answer 7

Mostly poultry but sometimes pigs.

Question 8

Where do most O157:H7 cases come from?

Answer 8

Contaminated beef

Question 9

Where does O157:H7 live?

Answer 9

In the rectum of cattle

Question 10

What are the food poisoning bacteria?

Answer 10

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

Question 11

What antibiotic are lots of campylobacter infections resistant to?

Answer 11

Ciprofloxacin

Question 12

Why are lots of campylobacter infections resistant to ciprofloxacin?

Answer 12

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

Question 13

What resistance is antibiotic resistant zoonotic infections associated with?

Answer 13

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

Question 14

What is now illegal to prevent fluoroquinolone resistant zoonotic infections?

Answer 14

Prophylactic treatment

Question 15

Do bacteria in the environment and flora cause infections?

Answer 15

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.

Question 16

What helps prevent O157:H7 food poisoning?

Answer 16

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

Question 17

What are the food testing limits for pathogenic bacteria?

Answer 17

Very strict

Question 18

What are the food testing limits for opportunistic bacteria?

Answer 18

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

Question 19

How do vegetables get contaminated with faecal bacteria?

Answer 19

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

Question 20

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

Answer 20

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

Question 21

What was done to all the faecal samples from HSTAR?

Answer 21

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

Question 22

What important resistance mechanisms were found in the dairy farms?

Answer 22

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

Question 23

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

Answer 23

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.

Question 24

What is cefquinome and why is resistance concerning?

Answer 24

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.

Question 25

What does use of antibiotics on farms cause?

Answer 25

High levels of resistance to that type of antibiotic

Question 26

Why is framycetin resistance found alongside cefquinome resistance?

Answer 26

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

Question 27

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

Answer 27

pMOO-32

Question 28

What is framycetin?

Answer 28

An aminoglycoside antibiotic.

Question 29

What selects for ampC producers?

Answer 29

Use of amoxicillin

Question 30

What selects for fluoroquinolone resistance?

Answer 30

Use of fluoroquinolones

Question 31

Why has antibiotic use on farms deceased?

Answer 31

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.

Question 32

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

Answer 32

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.

Question 33

Why has ampC mediated resistance not decreased?

Answer 33

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.

Question 34

Has fluoroquinolone resistance fallen in farms?

Answer 34

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.

Question 35

How important is different use in driving antibiotic resistance?

Answer 35

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.

Question 36

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

Answer 36

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.

Question 37

How would animals bacteria get across to humans?

Answer 37

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.

Question 38

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

Answer 38

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

Question 39

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

Answer 39

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.

Question 40

What is the FASRG database?

Answer 40

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

Question 41

What are FASRGs?

Answer 41

farm animal-specific resistance genes.

Question 42

Can FASRGs be found in human infections?

Answer 42

Yes, but at a lower percentage then in animals

Question 43

What do FASRGs give resistance to?

Answer 43

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

Question 44

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

Answer 44

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.

Question 45

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

Answer 45

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.

Question 46

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

Answer 46

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.

Question 47

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

Answer 47

They become humanised

Question 48

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

Answer 48

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.

Question 49

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

Answer 49

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.