Team:Edinburgh OG/HP/Gold Integrated
Gold Medal and Integrated Human Practices
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Expert Perspectives
We interviewed a number of people to learn more about how antibiotic resistance impacts them and how they think our project could fit into their work.
We learnt a lot from the experts we interviewed, especially with regards to the real world uses of PhagED. When we started the project, our plan was for PhagED to be used in spray form to clean hospital surfaces - one spray for the lysogenic phage and another for the lytic phage. While researching the project, we found that antibiotic resistance is as much of an issue in the farming world as it is in hospitals, so we also investigated this potential route for PhagED as part of our human practices.
Through discussions with experts from both the healthcare and animal industries, we realised that a spray wasn’t the best way to deploy our system.
In hospital settings, powdered detergents and dissolvable cleaning agents are commonly used instead of sprays. Therefore, we decided to focus on PhagED as a powder rather than a spray. As our computational model demonstrated, the provision of nutrients to the system enhances the ability of the phages to remove resistant bacteria. Nutrient powder could therefore be mixed with the powdered phages to create the most efficient possible PhagED. By encapsulating the powdered phages in different coatings, their rate of dissolving can be controlled - allowing the system to be applied in a single stage while ensuring that the lysogenic phages are the first to contact the resistant bacteria.
Powdered PhagED would also be applicable in farm environments, where it could be used for cleaning equipment etc., but also potentially as a food additive. For a product like this to be viable, it would have to be cost-effective and easily incorporated into current routines and treatments.
Below you can see the key points that we learnt from each expert and how they affected our plans for PhagED.
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Dr. Beth Reilly - Specialised in farm animals
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How often do you see evidence of antibiotic resistance in livestock?
We don’t test for resistance often as farmers don’t have a lot of money, so it isn’t that common you would go round culturing for resistances. Therefore there is a lot of antibiotic resistant bacteria that we don’t see, but it is actually much more common than you realise. For example farms are never that sterile, there are flies everywhere and dust in the air etc makes it hard to keep control over bacteria. Also, often ‘bad’ farmers try to save money by halving the dosage or sharing it between two animals, again increasing chance of resistance. As giving an animal lots of small doses is really time consuming (e.g. farmers have to catch the animal) often we prescribe a single high dose of antibiotic for an infection. This means there is a longer period at the end where the animal is exposed to a low level of antibiotics, which also can increase the chance of a new population of bacteria colonising within the animal and developing resistance. One antibiotic I give has a single dose and works for 7 days, which means it could last in the animal for a further week after the first infection is killed off at a low dose - creating opportunity for new bacteria to gain resistance!
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How do you sterilize equipment?
Iodine is used to sterilize boots and kit, surgery equipment is autoclaved by vets within a box which is only opened at the site of a surgery. We also carry ‘wet packs’ which is basically a sealed box full of alcohol, in which we can put instruments in so that they are semi-sterile, which can be used if you are doing a ‘dirty surgery’ (say an abyss drain) so you can sterilize a clamp to remove the infection. In terms of milking, there is environmental mastitis (bacterial infection of the udder) which they get from bedding and mechanical mastitis which is passed on through milking, so a lot of farms have iodine or chemical flushes which are circulated through the dairy machines after each cow.
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Do you think you could use PhagED as part of sterilizing equipment?
Breaking open a box of pre- autoclaved surgery equipment could be seen as counterintuitive and it would no longer be sterile. And whether it would be worth it would depend on how much it would cost, because money is everything to farmers. And it would be something the vets in theory would do which would be added to the farmer’s bill. In terms of the milking machines it’s possible you could add phages to the liners, which in some farms are empty for a couple of hours in a day. For example if a farmer had a very contagious batch of infectious bacteria they may be interested in using it. Or if the farmer could put it on their hands as sometimes the infection travels through their contact with lots of teats.
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Well we were also considering using PhagED as a soap, so maybe an hour before you interact with the animals you wash your hand with the first liquid containing phages then when you are at the farm site wash it with the other liquid. What would you think of that?
Yes that would work, so we could use it as a sterile surgery prep soap. That would be awesome because the worry is when you do a surgery that you could cause an unwanted infection. So if you know any infection you could cause would be treatable by antibiotics that would be great. So I think I would perhaps more see this working as a hand soap than for sterilizing equipment, as a hand soap would be easy - we currently already have alcoholic hand soaps outside all the pens so it would be relatively easy.
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How much do you think antibiotic resistance costs farmers?
Each farm is very different in that sense, some farms probably don’t have any resistance as they are very responsible, whereas others resistance issues all the time all the time, so it is difficult to quantify. Antibiotics are one of these things where we are really trying to reduce the usage and avoid using where we can - there has been a big drive for this in my vet teaching. A lot of this plays out in trying to encourage farmers to keep a clean environment and be responsible with their antibiotic use.
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How do you mostly deliver antibiotics?
We often try to only use spray antibiotics (commonly oxytetracyclines) on cuts rather than inject animals with systemic ones if the farm seems clean. So only on really dirty farms will we give systemic antibiotics. Antibiotic sprays can be found on every farm and every time animals cut themselves people use these. Farmers use this a lot because it’s easy.
Some vets (which I think is bad practice) during a surgery will empty an entire bottle of antibiotics inside the animal. Another really common time we give antibiotics is after a bad calving so you have had to put your hand in to help it along, and you try as much as you can to make sure it’s clean as obviously this is a sterile environment you are going into. The common bacteria which enter a calving from your skin are Step and Strap (Streptococcus and Staphylococcus), which can be very resistant.
One bacteria which is really hard to kill with antibiotics and is commonly the cause of mastitis is Staphylococcus aureus. I’ve definitely seen antibiotic resistance in udder infections but it is always really difficult to know in mastitis whether it was transmitted in the milking machine or from bedding or the air, and whether the antibiotic isn’t working because you picked the wrong antibiotic for the pathogen or the farmer didn’t deliver it or if this is real resistance. So it’s very difficult to know if this is resistance, although sometimes you get farmers saying ‘that drug doesn’t work on our farm’ which suggests this could be happening. However even then we can’t be sure, as they might just not like the drug simply because it is new and they are less confident on how to deliver it, or the antibiotic might alter the milk for longer periods as they can’t sell milk from a cow on antibiotics.
With chickens and pigs a lot of their seed is medicated, which basically makes an antibiotic broth - waiting to be drunk. We are trying to move the profession away from that because the issue with that is if everyone is eating normally they will get the adequate dose of antibiotics. But, if you get sick animal - which is the one that needs the antibiotics, it’s probably not going to eat as much as it should because it’s not feeling very well. So then it gets a half dose of antibiotics, making it much more likely for resistance to occur. And also with chickens they use a lot of spray antibiotics, so they sort of have a mist around the birds. So a lot of heavy uses of antibiotics are here which may be worth looking into.
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How could you incorporate our product in your practice? Specific areas? Specific equipment?
Where there is resistance that we know of, e.g. udders. For example if there is a farm which we know has a resistance problem for a particular bacteria - a spray for the milk machine could have a market. Although to implement this we you do have to think about how often the milk machines are in use and how long it would have to stay on the equipment between milking - so you are limited in time between calvings. Some large farms also have the parlour in nearly constant use. You could spray the inside of the lining of the teat - which is small and 2-3 cm in diameter.
Also it could be used during calvings, we always give antibiotics post difficult calvings, because normally a lot of fecal material enters and they are usually low in calcium as they are really tired so their cervix muscles don’t close properly. It’s common for vets to go without gloves during calvings so using a hand soap before this for calving and general operations. Although I doesn’t know if there is much resistance there because often you jab them with antibiotics and then if they aren't treated the farmer might go to their own medicine cabinets and jab them with different ones. But definitely some way of using this for calving could be very useful - or just general handsoap - even in hospitals for humans!
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Do you have any further suggestions for a way of using PhagED?
When a cow is on antibiotics the milk it produces cannot be sold for human consumption. So what a lot of farmers do instead of pouring it down the drain is give it to their calves. Vets are encouraging farmers not to do this because of the potential for antibiotic resistance to occur in calves, but also even pouring liquid laced with antibiotics down the drain is quite irresponsible, so you are meant to contain it for a few days so the drug breaks down. So if you had a powder which you could mix into it the then farmers would love it, because then they wouldn’t have to pour milk down the drain and can feed their calves. And if the bacteria could no longer be resistance then there wouldn’t be any worry with vets of farmers doing this.
Another option could be to use it as part of a treatment we already deliver to cow’s udders before birth when we dry them off (stop milking them ~60 days before calving). It used to be common to treat all the quarters (of an udder) with an antibiotic. But we are now going to a selective dry cow therapy where we only put antibiotics in the quarters that has an infection which requires it. It could be an interesting idea to add a bacteriophage to the teat sealant (a plug at the end of the udder) that we use to seal the teats from bacteria, so that if any infection did get in there (ideally none as you do it aseptically) it would be guaranteed to respond to antibiotics.
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Would you consider incorporating PhagED into your practice?
We are all working on minimising antibiotic resistance so it would be good to do, as there is this threat that we will no longer be able to treat our animals with antibiotics. So if we could make sure this doesn’t happen by using it I think this would be a really good product.
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- The biggest limitation is the time delay between the two treatments.
- Most infections in cows for his farm occur in udders and feet, and half of his cows will be given antibiotics in a given year because of this.
- Putting PhagED into a powdered form as a milk supplement would be sought after - if financially viable (<15p per litre).
Questions on practicality of using our product
What we learnt from Andrew McGregor?
If we wanted farmers to take up using PhagED on farms, it would have to be incorporated into practices they already routinely do, which are usually only conducted once. Therefore it would be important to find a way of encapsulating the lytic phages which would be released after a specific delay to allow lysogenic infection to occur first.
There is scope to use PhagED on farms, an easy area would be to add PhagED to current treatments farmers regularly use on their livestock, such as integrating PhagED into drying off treatment, footbaths and udder wipes. This could drastically reduce resistance. This is in agreement with what Dr. Reilly (the vet) said.
If calves could drink milk which has been made ‘safe’ from antibiotic resistant bacteria it would be a win win for farmers, many of whom already practice this anyway despite warnings.
