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<h2>Expert Perspectives</h2></li> | <h2>Expert Perspectives</h2></li> | ||
<p>We interviewed people who work with antibiotic resistance to learn more about how it impacts them and where PhagED could fit into their work.</p> | <p>We interviewed people who work with antibiotic resistance to learn more about how it impacts them and where PhagED could fit into their work.</p> | ||
− | + | <img style="float: right; width: 220px; margin: 15px 20px 15px 0px;" src="https://static.igem.org/mediawiki/2017/6/65/T--Edinburgh_OG--hpgold_fig2.png"> | |
<img style="float: right; width: 220px; margin: 15px 0px 15px 20px;" src="https://static.igem.org/mediawiki/2017/6/6b/T--Edinburgh_OG--hpgold_fig1.png"> | <img style="float: right; width: 220px; margin: 15px 0px 15px 20px;" src="https://static.igem.org/mediawiki/2017/6/6b/T--Edinburgh_OG--hpgold_fig1.png"> | ||
<p>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 | <p>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 farming as it is in hospitals, so we also investigated the potential for PhagED to be used with livestock as part of our human practices.</p> | + | and another for the lytic phage. While researching the project, we found that antibiotic resistance is as much of an issue in farming as it is in hospitals, so we also investigated the potential for PhagED to be used with livestock as part of our |
− | + | human practices.</p> | |
+ | |||
<p>Through discussions with experts from both healthcare and agriculture, we realised a spray was not the optimal method to deploy our system.</p> | <p>Through discussions with experts from both healthcare and agriculture, we realised a spray was not the optimal method to deploy our system.</p> | ||
− | + | ||
<p>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 | <p>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, | 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, | ||
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<a class="cd-faq-trigger" href="#0">How often do you see evidence of antibiotic resistance in livestock?</a> | <a class="cd-faq-trigger" href="#0">How often do you see evidence of antibiotic resistance in livestock?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>We often don’t test for resistance in farm vet practice as farmers don’t have a lot of money to spare, so it isn’t that common you would go round culturing for resistances. Therefore there could well be a lot of antibiotic resistant bacteria - hard to know without looking for them! Farms have bacteria everywhere (just like on your skin) so there is always a risk of disease.</p> | + | <p>We often don’t test for resistance in farm vet practice as farmers don’t have a lot of money to spare, so it isn’t that common you would go round culturing for resistances. Therefore there could well be a lot of antibiotic resistant |
− | <p>It is reported by vets that ‘bad’ farmers exist where they might try to save money by halving the dosage or sharing it between two animals, increasing the chance of selecting resistant bacteria. There are plenty of fantastic farmers out there that our very diligent with their antimicrobial usage.</p> | + | bacteria - hard to know without looking for them! Farms have bacteria everywhere (just like on your skin) so there is always a risk of disease.</p> |
− | <p>The phrase ‘that drug doesn’t work on our farm’ often raises levels of suspicion of resistant bacteria on farm. However, without culture and sensitivity we simply can’t make any assumptions. It could be something as simple as not giving the correct dose for the weight of the animal, not following the instructions (different frequency of administration) or not administering the drug properly.</p> | + | <p>It is reported by vets that ‘bad’ farmers exist where they might try to save money by halving the dosage or sharing it between two animals, increasing the chance of selecting resistant bacteria. There are plenty of fantastic farmers |
+ | out there that our very diligent with their antimicrobial usage.</p> | ||
+ | <p>The phrase ‘that drug doesn’t work on our farm’ often raises levels of suspicion of resistant bacteria on farm. However, without culture and sensitivity we simply can’t make any assumptions. It could be something as simple | ||
+ | as not giving the correct dose for the weight of the animal, not following the instructions (different frequency of administration) or not administering the drug properly.</p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">How do you sterilize equipment?</a> | <a class="cd-faq-trigger" href="#0">How do you sterilize equipment?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>Iodine is used to sterilize boots and waterproofs. Surgical equipment is autoclaved and stored in sterile packaging. We also carry ‘wet packs’ | + | <p>Iodine is used to sterilize boots and waterproofs. Surgical equipment is autoclaved and stored in sterile packaging. We also carry ‘wet packs’ which is basically a sealed box full of alcohol, in which we can put instruments in so that |
− | </p> | + | 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 reduce the risk of infection. |
+ | </p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">Do you think you could use PhagED as part of sterilizing equipment? </a> | <a class="cd-faq-trigger" href="#0">Do you think you could use PhagED as part of sterilizing equipment? </a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>Yes I think incorporating PhagED into the process of sterilizing could be an idea. Obviously, we hope that the sterilized equipment would have no bacteria present on them. However, it could be interesting to see if it could be incorporated into the washing of boots and waterproofs. The first step in seeing if this is needed is to try and culture bacteria from waterproofs after they have been cleaned to see if there is bacteria present. The other obvious question would be cost, time and ease of use.</p> | + | <p>Yes I think incorporating PhagED into the process of sterilizing could be an idea. Obviously, we hope that the sterilized equipment would have no bacteria present on them. However, it could be interesting to see if it could be incorporated into |
− | <p>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 and usually chemically cleaned. A hand wash aswell could help to stop the transmission of resistant bacteria; which could be really useful for a farm which has known bacterial resistance e.g. mastitis.</p> | + | the washing of boots and waterproofs. The first step in seeing if this is needed is to try and culture bacteria from waterproofs after they have been cleaned to see if there is bacteria present. The other obvious question would be cost, time and |
+ | ease of use.</p> | ||
+ | <p>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 and usually chemically cleaned. A hand wash aswell could help to stop the transmission of resistant | ||
+ | bacteria; which could be really useful for a farm which has known bacterial resistance e.g. mastitis.</p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">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?</a> | <a class="cd-faq-trigger" href="#0">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?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>Yes that could work, if we used second wash in combination with our sterile surgery prep soap. That would be awesome if we could no longer worry about the risk of causing an infection that is resistant to antimicrobials, with the knowledge that it would be treatable by antibiotics. I think I would perhaps more see this working as a hand soap than for sterilizing equipment, as a hand soap would be easy - seeing as we should all be washing our hands frequently. </p> | + | <p>Yes that could work, if we used second wash in combination with our sterile surgery prep soap. That would be awesome if we could no longer worry about the risk of causing an infection that is resistant to antimicrobials, with the knowledge that |
+ | it would be treatable by antibiotics. I think I would perhaps more see this working as a hand soap than for sterilizing equipment, as a hand soap would be easy - seeing as we should all be washing our hands frequently. </p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">How much do you think antibiotic resistance costs farmers?</a> | <a class="cd-faq-trigger" href="#0">How much do you think antibiotic resistance costs farmers?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>Each farm is very different in that sense, some farms probably don’t have any resistance as they are very responsible, whereas others may have resistance issues (but may not know), 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 veterinary course. A lot of this plays out in trying to reduce the need for them by encouraging farmers to keep a clean environment and reduce the risk of infection. Hence, enabling them to be responsible with their antibiotic use. In 2016, RUMA (responsible use of medicines in agriculture alliance) was set up to ensure that the concerns over antimicrobial resistance are dealt with appropriately. Here is the link to read up on the latest news from RUMA <a href="http://www.ruma.org.uk/">http://www.ruma.org.uk/</a></p> | + | <p>Each farm is very different in that sense, some farms probably don’t have any resistance as they are very responsible, whereas others may have resistance issues (but may not know), 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 veterinary course. A lot of this plays out in trying to reduce the need for them by encouraging farmers to keep a clean | ||
+ | environment and reduce the risk of infection. Hence, enabling them to be responsible with their antibiotic use. In 2016, RUMA (responsible use of medicines in agriculture alliance) was set up to ensure that the concerns over antimicrobial resistance | ||
+ | are dealt with appropriately. Here is the link to read up on the latest news from RUMA <a href="http://www.ruma.org.uk/">http://www.ruma.org.uk/</a></p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">How do you mostly deliver antibiotics?</a> | <a class="cd-faq-trigger" href="#0">How do you mostly deliver antibiotics?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>As vets we have many different routes of treatment from systemic (oral or injectable) or topical (sprays, ointments or intramammary tubes). We try to minimise the use of antibiotics where possible, only selecting appropriate antibiotics for the treatment of the disease concerned where necessary.</p> | + | <p>As vets we have many different routes of treatment from systemic (oral or injectable) or topical (sprays, ointments or intramammary tubes). We try to minimise the use of antibiotics where possible, only selecting appropriate antibiotics for the |
− | <p>Antibiotic sprays (e.g. Tetracyclines) can often be found in a farmer's medicine cabinet and used frequently. They are often used for the intended purpose. However, irresponsible use certainly does still occur. For instance, marking animals using the stockmarker part of the product when their is no indication for antibiotics.</p> | + | treatment of the disease concerned where necessary.</p> |
− | <p>A common time we give antibiotics is after a bad calving, as their is usually contamination of the uterus from the environment. The common bacteria are commensal skin bacteria and bacteria from faeces. It is important that we choose an antibiotic that will work for the types of bacteria we are expecting to be present.</p> | + | <p>Antibiotic sprays (e.g. Tetracyclines) can often be found in a farmer's medicine cabinet and used frequently. They are often used for the intended purpose. However, irresponsible use certainly does still occur. For instance, marking animals using |
− | <p>There are concerns over medicated feed, often used in the poultry and pig industry, where animals are medicated with antibiotics through the feed. This creates antibiotic broths; providing a source to selectively promote resistant bacteria. This aims to treat everything prophylactically, but may not be adequate treatment for the sick individuals if they have reduced feed or water intakes.</p> | + | the stockmarker part of the product when their is no indication for antibiotics.</p> |
− | <p>Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-resistant Staphylococcus pseudintermedius(MRSP) are very much a problem in small animal veterinary practice causing nasty skin conditions. In dairy practice, mastitis is often a big issue on farm and don’t always respond to the initial antibiotic treatment. The need for culture and sensitivity from milk samples in cases which haven’t responded to treatment is essential to know if we are dealing with resistant bacteria.</p> | + | <p>A common time we give antibiotics is after a bad calving, as their is usually contamination of the uterus from the environment. The common bacteria are commensal skin bacteria and bacteria from faeces. It is important that we choose an antibiotic |
+ | that will work for the types of bacteria we are expecting to be present.</p> | ||
+ | <p>There are concerns over medicated feed, often used in the poultry and pig industry, where animals are medicated with antibiotics through the feed. This creates antibiotic broths; providing a source to selectively promote resistant bacteria. This | ||
+ | aims to treat everything prophylactically, but may not be adequate treatment for the sick individuals if they have reduced feed or water intakes.</p> | ||
+ | <p>Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-resistant Staphylococcus pseudintermedius(MRSP) are very much a problem in small animal veterinary practice causing nasty skin conditions. In dairy practice, mastitis is often a | ||
+ | big issue on farm and don’t always respond to the initial antibiotic treatment. The need for culture and sensitivity from milk samples in cases which haven’t responded to treatment is essential to know if we are dealing with resistant | ||
+ | bacteria.</p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">How could you incorporate our product in your practice? Specific areas? Specific equipment?</a> | <a class="cd-faq-trigger" href="#0">How could you incorporate our product in your practice? Specific areas? Specific equipment?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>Where there is resistance that we know of, e.g. sensitivity cultures from milk samples from mastitic cows, it would be great to try and incorporate this into their treatment. | + | <p>Where there is resistance that we know of, e.g. sensitivity cultures from milk samples from mastitic cows, it would be great to try and incorporate this into their treatment. For example if there is a farm which we know has a resistance problem |
− | <p>Using a hand soap before procedures such as calving and operations could be useful to ensure that, even if any bacteria is present post scrubbing for surgery, it will be susceptible to antibiotics. | + | for a particular bacteria - a spray for the milk machine could potentially have a place in the market. Although to implement this 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 |
− | </p> | + | between milking - so you are limited in time between milkings. Some large farms also have the parlour in nearly constant use. Best to ask the farmers about how easy this would be to incorporate into their daily routines. .</p> |
+ | <p>Using a hand soap before procedures such as calving and operations could be useful to ensure that, even if any bacteria is present post scrubbing for surgery, it will be susceptible to antibiotics. Even a general hand soap for every day use for | ||
+ | everyone could be useful - especially in hospitals where there is often known bacterial resistance! | ||
+ | </p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">Do you have any further suggestions for a way of using PhagED?</a> | <a class="cd-faq-trigger" href="#0">Do you have any further suggestions for a way of using PhagED?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>When a cow is on antibiotics the milk it produces cannot be sold for human consumption. Many farmers understandably don’t want to pour this down the drain - as that would be like chucking your wallet in the bin. So some farmers choose to feed this to their calves. However, as vets we have to encourage farmers not to do this because of the potential for antibiotic resistance to occur in calves. Having said that, is it responsible to pour milk containing antibiotics down the drain?</p> | + | <p>When a cow is on antibiotics the milk it produces cannot be sold for human consumption. Many farmers understandably don’t want to pour this down the drain - as that would be like chucking your wallet in the bin. So some farmers choose to feed |
− | <p>If PhagED could be mixed into this discarded antibiotic milk then farmers would love it, because it would appease both vets and farmers. No more pouring milk down the drain nor risk of transmission of resistant bacteria to calves. I guess the next step would be to work out the common bacteria present in milk that is discarded and develop phages to target that mix of bacteria.</p> | + | this to their calves. However, as vets we have to encourage farmers not to do this because of the potential for antibiotic resistance to occur in calves. Having said that, is it responsible to pour milk containing antibiotics down the drain?</p> |
− | <p>Another option could be to use it as part of a treatment we already deliver to cow’s udders before they calve when we dry them off (stop milking them) which usually happens 60-80 days before their due date. It used to be common to treat all the quarters (of an udder) with an antibiotic, but we now use selective dry cow therapy where we only put antibiotics into the quarters of the udder that has an infection and requires treatment. The rest of the quarters are just given a teat sealant to prevent bacteria entering the udder. It could be an interesting idea to add a bacteriophage to the teat sealant that we use, so that if any infection did get in there (ideally none as you do it aseptically) it would be guaranteed to respond to antibiotics.</p> | + | <p>If PhagED could be mixed into this discarded antibiotic milk then farmers would love it, because it would appease both vets and farmers. No more pouring milk down the drain nor risk of transmission of resistant bacteria to calves. I guess the next |
+ | step would be to work out the common bacteria present in milk that is discarded and develop phages to target that mix of bacteria.</p> | ||
+ | <p>Another option could be to use it as part of a treatment we already deliver to cow’s udders before they calve when we dry them off (stop milking them) which usually happens 60-80 days before their due date. It used to be common to treat all | ||
+ | the quarters (of an udder) with an antibiotic, but we now use selective dry cow therapy where we only put antibiotics into the quarters of the udder that has an infection and requires treatment. The rest of the quarters are just given a teat sealant | ||
+ | to prevent bacteria entering the udder. It could be an interesting idea to add a bacteriophage to the teat sealant that we use, so that if any infection did get in there (ideally none as you do it aseptically) it would be guaranteed to respond | ||
+ | to antibiotics.</p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> | ||
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<a class="cd-faq-trigger" href="#0">Would you consider incorporating PhagED into your practice?</a> | <a class="cd-faq-trigger" href="#0">Would you consider incorporating PhagED into your practice?</a> | ||
<div class="cd-faq-content"> | <div class="cd-faq-content"> | ||
− | <p>We are all working on minimising antibiotic resistance so it would be good to do everything that we can. There is the growing threat vets will no longer be able to treat animals with antibiotics when they need it if we don’t use them responsibly. So if we use new technologies, such as PhagED, to help reduce the risk of resistant bacteria then I think this would be a really good product.</p> | + | <p>We are all working on minimising antibiotic resistance so it would be good to do everything that we can. There is the growing threat vets will no longer be able to treat animals with antibiotics when they need it if we don’t use them responsibly. |
+ | So if we use new technologies, such as PhagED, to help reduce the risk of resistant bacteria then I think this would be a really good product.</p> | ||
</div> | </div> | ||
<!-- cd-faq-content --> | <!-- cd-faq-content --> |
Revision as of 02:25, 2 November 2017
Integrated Human Practices
-
Expert Perspectives
We interviewed people who work with antibiotic resistance to learn more about how it impacts them and where PhagED could fit into their work.
![](https://static.igem.org/mediawiki/2017/6/65/T--Edinburgh_OG--hpgold_fig2.png)
![](https://static.igem.org/mediawiki/2017/6/6b/T--Edinburgh_OG--hpgold_fig1.png)
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 farming as it is in hospitals, so we also investigated the potential for PhagED to be used with livestock as part of our human practices.
Through discussions with experts from both healthcare and agriculture, we realised a spray was not the optimal method 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 we provide full interview transcripts with the expects and outline how this information affected the development of PhagED.
-
Dr. Beth Reilly - Farm Animal Veterinary Surgeon
-
How often do you see evidence of antibiotic resistance in livestock?
We often don’t test for resistance in farm vet practice as farmers don’t have a lot of money to spare, so it isn’t that common you would go round culturing for resistances. Therefore there could well be a lot of antibiotic resistant bacteria - hard to know without looking for them! Farms have bacteria everywhere (just like on your skin) so there is always a risk of disease.
It is reported by vets that ‘bad’ farmers exist where they might try to save money by halving the dosage or sharing it between two animals, increasing the chance of selecting resistant bacteria. There are plenty of fantastic farmers out there that our very diligent with their antimicrobial usage.
The phrase ‘that drug doesn’t work on our farm’ often raises levels of suspicion of resistant bacteria on farm. However, without culture and sensitivity we simply can’t make any assumptions. It could be something as simple as not giving the correct dose for the weight of the animal, not following the instructions (different frequency of administration) or not administering the drug properly.
-
How do you sterilize equipment?
Iodine is used to sterilize boots and waterproofs. Surgical equipment is autoclaved and stored in sterile packaging. 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 reduce the risk of infection.
-
Do you think you could use PhagED as part of sterilizing equipment?
Yes I think incorporating PhagED into the process of sterilizing could be an idea. Obviously, we hope that the sterilized equipment would have no bacteria present on them. However, it could be interesting to see if it could be incorporated into the washing of boots and waterproofs. The first step in seeing if this is needed is to try and culture bacteria from waterproofs after they have been cleaned to see if there is bacteria present. The other obvious question would be cost, time and ease of use.
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 and usually chemically cleaned. A hand wash aswell could help to stop the transmission of resistant bacteria; which could be really useful for a farm which has known bacterial resistance e.g. mastitis.
-
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 could work, if we used second wash in combination with our sterile surgery prep soap. That would be awesome if we could no longer worry about the risk of causing an infection that is resistant to antimicrobials, with the knowledge that it would be treatable by antibiotics. I think I would perhaps more see this working as a hand soap than for sterilizing equipment, as a hand soap would be easy - seeing as we should all be washing our hands frequently.
-
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 may have resistance issues (but may not know), 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 veterinary course. A lot of this plays out in trying to reduce the need for them by encouraging farmers to keep a clean environment and reduce the risk of infection. Hence, enabling them to be responsible with their antibiotic use. In 2016, RUMA (responsible use of medicines in agriculture alliance) was set up to ensure that the concerns over antimicrobial resistance are dealt with appropriately. Here is the link to read up on the latest news from RUMA http://www.ruma.org.uk/
-
How do you mostly deliver antibiotics?
As vets we have many different routes of treatment from systemic (oral or injectable) or topical (sprays, ointments or intramammary tubes). We try to minimise the use of antibiotics where possible, only selecting appropriate antibiotics for the treatment of the disease concerned where necessary.
Antibiotic sprays (e.g. Tetracyclines) can often be found in a farmer's medicine cabinet and used frequently. They are often used for the intended purpose. However, irresponsible use certainly does still occur. For instance, marking animals using the stockmarker part of the product when their is no indication for antibiotics.
A common time we give antibiotics is after a bad calving, as their is usually contamination of the uterus from the environment. The common bacteria are commensal skin bacteria and bacteria from faeces. It is important that we choose an antibiotic that will work for the types of bacteria we are expecting to be present.
There are concerns over medicated feed, often used in the poultry and pig industry, where animals are medicated with antibiotics through the feed. This creates antibiotic broths; providing a source to selectively promote resistant bacteria. This aims to treat everything prophylactically, but may not be adequate treatment for the sick individuals if they have reduced feed or water intakes.
Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-resistant Staphylococcus pseudintermedius(MRSP) are very much a problem in small animal veterinary practice causing nasty skin conditions. In dairy practice, mastitis is often a big issue on farm and don’t always respond to the initial antibiotic treatment. The need for culture and sensitivity from milk samples in cases which haven’t responded to treatment is essential to know if we are dealing with resistant bacteria.
-
How could you incorporate our product in your practice? Specific areas? Specific equipment?
Where there is resistance that we know of, e.g. sensitivity cultures from milk samples from mastitic cows, it would be great to try and incorporate this into their treatment. 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 potentially have a place in the market. Although to implement this 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 milkings. Some large farms also have the parlour in nearly constant use. Best to ask the farmers about how easy this would be to incorporate into their daily routines. .
Using a hand soap before procedures such as calving and operations could be useful to ensure that, even if any bacteria is present post scrubbing for surgery, it will be susceptible to antibiotics. Even a general hand soap for every day use for everyone could be useful - especially in hospitals where there is often known bacterial resistance!
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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. Many farmers understandably don’t want to pour this down the drain - as that would be like chucking your wallet in the bin. So some farmers choose to feed this to their calves. However, as vets we have to encourage farmers not to do this because of the potential for antibiotic resistance to occur in calves. Having said that, is it responsible to pour milk containing antibiotics down the drain?
If PhagED could be mixed into this discarded antibiotic milk then farmers would love it, because it would appease both vets and farmers. No more pouring milk down the drain nor risk of transmission of resistant bacteria to calves. I guess the next step would be to work out the common bacteria present in milk that is discarded and develop phages to target that mix of bacteria.
Another option could be to use it as part of a treatment we already deliver to cow’s udders before they calve when we dry them off (stop milking them) which usually happens 60-80 days before their due date. It used to be common to treat all the quarters (of an udder) with an antibiotic, but we now use selective dry cow therapy where we only put antibiotics into the quarters of the udder that has an infection and requires treatment. The rest of the quarters are just given a teat sealant to prevent bacteria entering the udder. It could be an interesting idea to add a bacteriophage to the teat sealant that we use, 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 everything that we can. There is the growing threat vets will no longer be able to treat animals with antibiotics when they need it if we don’t use them responsibly. So if we use new technologies, such as PhagED, to help reduce the risk of resistant bacteria then I think this would be a really good product.
- Antibiotic resistance is a serious issue that vets are keen to find a solution for, but it is complicated by a conflict of interest with farmers.
- Using PhagED in the form of a spray to sterilize surgery equipment is not that practical. Using it as a soap, incorporating it into treatments or using it as a food additive would be a better application.
- Staphylococcus aureus is also very prevalent in farming as it is in hospitals. Therefore MecA would be a good target to first launch PhagED against. But it would be important for PhagED to have a number of targets to be worthwhile.
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Questions on practicality of using our product
What we learnt from Dr. Beth Reilly?
This means there is large scope for using PhagED in their practice as they can be more confident that any antibiotics they prescribe would be less likely to produce resistance, even if farmers cut corners.
As a team we had previously never considered using PhagED as a powder to add to food, but from talking to Dr. Reilly this option seems like an obvious choice for delivering the system, especially as feed is a large area where resistance arises across all livestock. Similarly, adding PhagED to treatments which are already routinely given to livestock was also not something we had thought of, but it seems there is large scope for this. The idea of using this as a soap remains popular.
Predicting which bacteria will cause an infection is very difficult, so if we wanted PhagED to work properly we would need to have phages targeting multiple genes.
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Andrew McGregor - Scottish Dairy Farmer
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How often do animals need antibiotics?
I roughly have 400 cattle, 200 sheep, out of the 400 cattle half of them will get antibiotic treatment in a year.
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Where do most infections come from in cattle?
When the cows become dry (stop producing milk before a calving) half of the herd get get preventative pre-antibiotic treatment, as the udder is the most common area for infections in this period. The feet of our cattle too is very prone to infections.
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How often do you sterilize equipment?
After every milking they get sterilized. The milking parlour works by having a machine which can milk up to 100 cows at once, where an anesthetic wash of chlorinated alkaline detergent is circulated around the equipment, which should kill the bacteria.
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How do you contain disease in your livestock?
We have a quarantine centre milking unit, so we milk them separately to ensure they are not using the same equipment as the other ones. We also have a quarantine area, basically a separate tent where we will keep them while they are sick.
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Have you ever experienced antibiotic resistance in your cattle - i.e. so they needed more antibiotics on top of what they had?
The drugs have always worked in the sense that I have never seen pure resistance, however in the cows sometimes you do see reduced effectiveness of treatment. So they remain ill for longer than expected.
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We’ve spoken to a vet, and she has some ideas of how to integrate PhagED into farming practice, so I wanted to see if you think they are any good?
Use it in a powder form to add to milk taken from a cow currently on antibiotics, so that it can be given to calves. The vet told me farmers often give this milk to calves as it cannot be sold due to it containing antibiotics.
Incorporating your product as a powder to add to milk is a valid idea with a clear cost benefit of doing it, so that is definitely a possible route you could take with your product. Farmers would definitely be interested! For it to be financially viable it would have to offset the costs of getting new milk for calves; milk current sells for around 25-30p a litre, a calf will drink 4 litres a day so buying in new milk will cost around £1 a day per calf. As the cow still has to be milked the time cost of milking it then throwing it away should also be considered. So if it was in powdered form and costs even as much as 15p per litre it would be worth it for farmers. Having a time delay of adding a second powder however may be off-putting. One company which might be worth talking to about this idea is Britmilk, who currently supply milk to calves with added supplements.
The next suggestion Dr. Reilly had was to use it to spray the inside of the milking device which is attached to the udders.A spray is a big stumbling block if there are two you have to use, one could work at a push, if you had it in the right format. For example a spray is actually not a great way of using it, a modern parlour has milking machine that is very complicated and made of many parts, and we don’t individually spray the equipment. However if you could circulate a water solution fluid through it all that could be more viable. However when we do bacteria testing in the parlour we found it was actually getting cleaned quite well between milkings; the problem was more the cows picking up the bacteria from their bedding or the fields onto their teats, which is why the biggest challenge in terms of sickness for the cows is getting dried off, not during milking. So if you could somehow incorporate this into the drying off stage that might be a better way to use this.
That links in very nicely with the next application suggested by the vet: using PhagED to cover the teat sealant or within the pre-antibiotic (used 60 days before a calving is due).Yes this is where there is large scope for your product. Definitely this seems like the obvious area to use it, this was the first thing that came to my mind when you started talking.
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What do you think about using it as a soap? So maybe you would wash your hand with the first soap in the morning, then wash it with the other soap when you get to the field, just before interacting with the animals.
I’m afraid that idea is not screaming out at me as something that farmers would pick up! Using it in a powdered form or teat sealant would seem a lot more practical to farmers. I suppose vets might like to use that for operations though, which seems to be another obvious area to use it.
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Would you have any concerns about using our product?
No I don’t think so, farmers are continually looking for ways to be more cost efficient and streamlined. So when people try and sell us products you just have to convince us it is worthwhile, and ensure it makes any sense. So it needs to be marketed well!
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Do you have any other suggestions for how we could use or sell PhagED?
Before drying off again the way we try and prevent bacteria getting into the udder is by using antiseptic wipes to clean the teat before we insert it. So incorporating the phages into the wipes could be a really good idea because as I said, that is where most of the infections come from rather than the equipment. A similar line is that the teats do have to be cleaned before milking the cow, as the bacteria they pick up mostly comes from outside the parlour.
Another area this could be used would be to tackle dermatitis (a common infection on the feet). To try stop this we walk cows through foot baths with antibiotics and antiseptic chemicals, so maybe you could treat them by adding the phages to the baths. Although, to feasibly implement this (if you needed to provide two different liquids) you could have a footbath in the day with the first phage and footbath in the night with the second. Or two footbaths directly one after another. Farmers would not adhere to something which means the footbaths have to be taken 2 hours apart, as once the cattle are out for the day they wouldn’t want to bring them in again until they have to in the evening. So having a time delay of even an hour wouldn’t work.
PhagED could potentially be something to sell to companies which directly sell to farmers, if they could incorporate it into the cleaning products that we already use then that would be great. I definitely think adding PhagED to existing products would get the best uptake.
- 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).
![](https://static.igem.org/mediawiki/2017/e/ef/T--Edinburgh_OG--hpgold_fig4.png)
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.
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Dr Yusuf Ali Lalloo - General Practitioner
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Where does resistance mainly occur in medicine?
Operating theatres are a big source of antibiotic resistant bacteria - this is because they are a difficult area to keep sterile so it would be useful to have a system to help keep resistant bacteria out. An example which comes to mind is using PhagED for dangerous surgeries like spinal surgeries, where it’s difficult to get antibiotics to reach the infected area. Therefore it would be useful to have something that can ensure the bacteria in that area are only sensitive to antibiotics.
It may also be useful to put PhagED down drains as flushing antibiotics away into the environment is also risky.
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How is equipment sterilized in hospitals?
Hospitals normally use disposable equipment - they even throw away a lot of metal instruments, producing large amounts of waste. Wipes are often used for surface cleaning. They only autoclave major surgical materials, as it’s cheaper to do this than autoclave large amounts of equipment. Things also often come as kits now for certain procedures. So you have one sterile pack that you open once rather than having packs of scissors etc.
In surgeries patients often have ‘skin preps’, so antiseptic liquids are washed over the site where the surgery will take place. Suppliers normally sterilise that sort of equipment before it comes to the hospital.
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How does antibiotic resistance arise in hospitals?
As a GP I’ve seen a lot of people suffering from antibiotic resistance - for example, people who had a lot of antibiotics as a child, or who had a gut infection. The more antibiotics people take, the more likely they are to be infected with resistant bacteria. Because of this certain antibiotics in Scotland need to be approved by a microbiologist before they can be used. In hospitals IV antibiotics tend to cause a lot of resistance, so often people who have been treated by these can’t be treated by regular antibiotic tablets and need to have IV antibiotics again.
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How do you think we could use PhagED in hospitals? We think sterilizing equipment or using as a hand soap could be beneficial.
For hospital use it would make sense to have your product to be added to sterilised equipment before packaging and made by a reputable dealer. The main sources of infections in spinal surgeries etc. arise from bacteria previously living on the patient’s skin or clothes. Thus for skin preps, doctors use ChloraPrep™ applied to the skin, usually in 2 or 3 rounds. So if you could integrate PhagED into that it could be useful too. In terms of soaps, they need to be non-abrasive, hypo-allergenic. Dispensers should ideally be hands-free, one per bed for each patient. So if PhagED fits that criteria it could work.
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How do hospitals deal with outbreaks of antibiotic resistance?
Deep cleaning resistance-contaminated areas normally take about 5 days. Microbiology departments regularly culture bacteria to check the resistance. In bad instances, the whole room might have to be redecorated - walls, carpets ripped out etc. Deep cleans aren’t super common, but also not super rare. Normally they’re not necessary if you can identify the source of the infection, and procedures for dealing with resistance are improving.
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How do doctors decide which antibiotics to prescribe?
There are guidelines about which antibiotics to use. Doctors are less “antibiotic-happy” these days. They used to treat the most likely bacteria and culture in the background, but now they wait for a culture before they treat.
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Summary (click to open)
We spoke to Ali to gain a doctor’s perspective on the antibiotic resistance problem and how our project could help solve it.
He emphasised the importance of removing antibiotic resistant bacteria from operating theatres. These areas are difficult to keep completely sterile, but using phage to remove antibiotic resistant bacteria would ensure that any infections that occur are simpler to treat.
We asked him about current procedures and the places he thought our project could fit best. The skin is a major source of infection during surgeries, so incorporating PhagED into skin preps and soaps could be incredibly useful. Current skin preps are typically chlorhexidine gluconate and alcohol-based, and soaps are also often alcohol-based. Because alcohol can kill certain phages, any soaps we created would have to take this into account. It’s also important that any soaps used are non-abrasive and hypoallergenic. Wipes are often used for cleaning surfaces, so these could potentially be imbued with PhagED - perhaps with one wipe for lysogenic phages and a second for lytic.
We also discussed the current state of antibiotics and antibiotic resistance. Ali sees a large number of people suffering from infections by antibiotic-resistant bacteria, especially patients who took a large number of antibiotics as children or who have previously suffered from gut infections. IV antibiotics are also a major cause of resistance, and patients treated with these can often no longer be treated with standard antibiotics. In Scotland, a number of antibiotics must be approved by a microbiologist before they can be administered, in an effort to reduce their unnecessary use and stop the development of resistance. It is becoming the norm for doctors to wait for culture results before prescribing antibiotics, rather than preemptively prescribing for the most likely bacteria.
- The majority of hospital equipment is disposable.
- Doctors often wait for a culture before deciding on a antibiotic.
- Deep cleaning hospital rooms can be very time consuming (take up to five days) and exhaustive.
- Soaps are found by every bed and have to be universally useable by everyone.
![](https://static.igem.org/mediawiki/2017/e/e8/T--Edinburgh_OG--hpgold_fig5.jpg)
What we learnt from Dr. Yusuf Ali Lalloo?
This means that for us to try and integrate PhagED for sterilizing equipment it would be most beneficial to talk to the companies which produce the disposable equipment for hospitals. Therefore selling it as a spray directly to hospitals to sterilize their own equipment probably isn’t viable.
Therefore if we wanted to ever develop PhagED in pill form with an antibiotic, there would be a high certainty that the correct phages would be delivered, as doctors already know which bacteria are being targeted.
This means removing antibiotic resistant bacteria can be highly time consuming, and thus costly for hospitals. Therefore a product like PhagED could be incredibly useful for reducing the risk of this happening.
If we wanted to integrate PhagED as a soap it would have to be tested carefully to not harm anyone. It may be difficult however to integrate PhagED in this way as the soaps often are alcohol-based, which kills phages.
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Karine Moore - Hospital Domestic
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What methods do you currently use to clean surfaces in the hospital? E.g. do you use cleaning sprays, wipes etc.?
For table surfaces/countertops/patients personal tables we use a liquid detergent dissolved in hot water, and use disposable paper towels with one square for each surface. For sinks and toilets we use a powder detergent disinfectant. In toilets it is applied to a wet toilet bowl and used with the toilet brush, and in the case of the sink a square of disposable paper is wet with water and a small amount is put on the damp towel and rubbed into the sink and then rinsed away with water. For floors in standard bedrooms and 6 bed wards we use the same liquid detergent used for cleaning surfaces/countertops/etc and dissolve this with hot water. For normal toilets in standard single rooms and 6 bed wards we dissolve the powder detergent disinfected used on toilets and sinks with hot water. The mop heads we use are fabric and are removable, and machine washed and tumble dried after each shift. These are removed and placed into plastic bags by domestics on shift upon entry into a new ward. PPE (Personal Protective Equipment) is worn at all times by domestics when cleaning, which consists of colour co-ordinated disposable aprons and medical grade disposable gloves, which are removed and replaced after the completion of each area.
For barrier rooms (high infection rooms such as C. difficile, MRSA, bird/swine flu, Hepatitis C) both the surface bucket and mop bucket are filled with a solution comprised of one “chlorine releasing disinfectant tablet with detergent” to one litre of hot water. These are used with the same disposable mop head and paper towels and the same procedure used to clean the room. The same powder detergent disinfectant is used for the toilets and sink. Once a domestic is inside a barrier room (single or 6 bed) they are not able to leave until the room is fully cleaned and remove their PPE as they are leaving the room and place this in the clinical waste bin provided. If the room has an airborne virus this PPE will include a mask alongside the standard disposable apron and medical grade disposable gloves.
In the case of a patient discharge the room is cleaned as a above with the chlorine tablet solution. However as each item is thoroughly cleaned it is removed from the room (this includes bedsides tables, chairs, bins, bed etc) and the floor is mopped with the chlorine solution and scrubbed with a disposable scrubbing pad and scrubber machine. The floor is then mopped again and allowed to air dry. If in a room with curtains or a 6 bed ward where divider screens are in use, these are removed and placed in soluble infection control bags and cleaned by linen staff and are replaced. If the bathroom has a shower curtain this is removed by domestic staff and placed in a bucket with the chlorine tablet solution (1:1 ratio) and allowed to soak for an extended period of time before being rinsed and hung back up.
If there is a blood/urine/faeces/sick spillage this is removed by nursing staff, but is done using the chlorine tablets mentioned above dissolved in hot water at a 1:1 ratio, with the exception of a blood spill where the ratio is 10:1.
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Does antibiotic resistance impact your work? How often do you see instances of antibiotic resistance? E.g. having to deep clean rooms where infections with resistant bacteria have occurred.
Antibiotic resistance impacts my work as it is the role of the domestic to maintain a safe and clean ward for patients, visitors and staff, and this is harder to achieve if bacteria are resistant to antibiotics and cleaning solutions. I experience instances of antibiotic resistance in every shift I work, as there is a high level of barrier/high infection rooms on my ward and in the surrounding wards on my level. These vary in severity, but a deep clean is always necessary in the room after the patient has been discharged (as mentioned above).
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What is your opinion of the project? Would you be willing to use this system to clean surfaces and/or your skin? Can you foresee any issues with this system?
I think this project is well founded and could become incredibly useful to NHS staff should it prove successful at rendering bacteria more susceptible to cleaning solutions, especially in the case of MRSA and C. difficile, both of which have high rates of being contracted in hospitals. Visitors and staff are warned about taking extra care when dealing with these cases as cross-contamination can happen easily. For example when dealing with a patient who has C. difficile, not only is it good practice to wash your hands afterwards but it is mandatory, as the hand gels in use do not remove C. difficile from your hands and only washing with hot water and the provided hand soap can do this. If the project was successful it would be incredibly useful to utilize this method in hand soaps and hand gels to minimise the risk of cross infection by staff and visitors, with more focus on hand gels as it mostly the only form of disinfection visitors use (if at all) when entering and leaving the ward. It is standard procedure to wash your hands and use hand gels after dealing with all patients and in between touching difference surfaces, especially in a ward setting. In all wards for all staff it is mandatory to have the hand up to the elbows exposed to avoid cross contamination via clothing.
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In what other ways do you think antibiotic resistant bacteria can be combated? E.g. alternative cleaning methods, changes in the way antibiotics are prescribed.
I do think that we as a society are too dependent on antibiotics and prescription drugs in general, and would be happy if more patients would be willing to try other methods first before resorting to prescription medication, and it is an approach I have started to adopt myself.
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Summary (click to open)
Karine has worked as a hospital domestic for a number of years and one of her main duties is cleaning various parts of the hospital including patients’ bedrooms and bathrooms. By speaking to her we were able to gain valuable insights into current cleaning procedures and how our project could be effectively implemented in hospitals.
She encounters infections with antibiotic resistant bacteria during every shift she works, though the severity of infections varies. Rooms where these infections occur are deemed “barrier rooms” and require special cleaning procedures. For these “deep cleans”, domestics wear personal protective equipment including an apron, a mask and gloves, and they are not permitted to remove this PPE and leave the room until cleaning is completely finished.
She typically uses powdered detergents for cleaning surfaces such as sinks, and liquid detergents and disposable mops for floors. For cleaning barrier rooms or spillages of bodily fluids, dissolvable chlorine tablets are used.
- Powders are used mostly for disinfecting surfaces rather than sprays, as spray bottles are easily contaminated once opened.
- They mix the powders with water and chlorine.
- Using PhagED as a soap has huge potential, as soaps are used by all staff and visitors to the hospital.
![](https://static.igem.org/mediawiki/2017/a/a4/T--Edinburgh_OG--hpgold_fig6.jpg)
What we learnt from Karine Moore?
Therefore producing PhagED as a powder would be much more beneficial than a spray.
This means there is scope to develop a method of encapsulating the lytic phage in something which dissolves in water - this would provide the time delay to deliver the lytic after the lysogenic treatment (simultaneous delivery would save cleaning the same room an hour later).
This also means we would need our phages to survive in contact with chlorine. Fortunately research has already been conducted on T7-like phages of Pseudomonas aeruginosa which demonstrates they can survive.
Zhang et al. showed if you mix these phages with chlorine tough biofilms are significantly reduced. Thus this could be a method of simultaneously destroying biofilms and reintroducing antibiotic susceptibility.
Again, we might need to look at how you would implement the lysogenic and lytic phage together, such as having two dispensers or a lytic phage that isn’t immediately active.