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Capstone appraising inc for money csumb capstone festival 2016 writing song lyrics in a paper ´╗┐as Neil said I work at the University of Bristol I'm not a clinician I'm a biochemist who turned into a microbiologist I've worked on antimicrobial resistance for nearly 20 years since before anybody else thought it was a problem and gratified to see so many people turning up today and I think it's indicative that generally awareness around AMR is increasing and I did a talk in a pub on Monday night there's about a hundred people in a pub to speak so to listen to me speak about antimicrobial resistance feels a bit like that here actually with the bar but you know I gave about half an hour talk I thought they'd all just run to the bar but we had a half an hour of questions afterwards from the general public and I think the public are aware of the issue they're becoming increasingly engaged and educated about the issue and I think it's therefore important that we all sort of keep up with that and keep up the pressure to try and deal with some of the problems that we know about and to actually do some research and so I want to talk about some of the background and some of the research that we're doing today around selection and transmission of antimicrobial resistance in animals and how that then might affect humans acronyms I'll probably use AMR I might talk of antibiotics or antimicrobials what I really mean antibacterial drugs and antibacterial drug resistance obviously lots of other things are important but I'm specifically talking about antibacterials okay and the primary driver for the project that I'm going to talk about today is the issue around the developed world and the fact that until microbial resistance is predominantly an issue around healthcare associated infections now actually the problem of AMR around the world is much much much much bigger than that and we shouldn't forget that in many parts of the world access to effective antimicrobials is a real problem and there are huge problems around TB and gonorrhea and other issues of organisms that have developed resistance but we really I want to talk about opportunistic infection sure that many of you will be thinking about opportunistic infections on a day to day basis in your professions these sorts of numbers you all know better than I probably but the point I want to pick up on is that a significant proportion if not a majority of these infections are caused by E coli which is a bacterium that's found in human and animal feces okay so we all carry around with us and so do I pretty much all animals as well so the link if you like that I'm going to draw between humans and animals is around predominantly E coli because they have it we have it and it's a big problem in terms of opportunistic infections because of opportunistic infections and other infections which are transmissible we need antibiotics of course I was born in 1973 so something happened about the time that I was born basically they stopped really developing me on to microbials it's not my fault basically what happened was all of these antimicrobial classes most of which we still use today will literally dugout the ground their natural resources and they were relatively easy to find they took a bit of an effort but relatively easy and relatively cheap to find once they found all these they kind of thought oh well I spend our money on something else we've got plenty and obviously after that point resistance has started to become more of an issue and we've lost to a certain extent some of the skills that were necessary to discover these antimicrobials but also because we'd already discovered all the easy ones to find it's more difficult to find new ones that's for someone else to talk about I just wanted really for you to get into your mind the ideas of these natural products you can find these antimicrobials in your back garden at home okay they're all around us and of course we're all familiar with Fleming who supposedly accidentally discovered penicillin because a mold blew in through an open window I've just been reading a book by Richard lakhs called the mold in dr. Flores coat and actually it sort of debunks this apparently this was kind of a made-up story it never really happened he was basically testing pretty much anything he could get his hands on chucking it on plates to see if he could find something that would kill bacteria because a lot of people don't realize that he actually discovered a lysozyme which is a substance we produce as a natural defense against bacteria anyway he discovered it it's around us all over and yet it's therefore not surprising to me but it is surprising to a lot of people that resistance developed so rapidly so for example we already knew about penicillin resistance before penicillin was clinically used and penicillin resistance in some organisms emerged incredibly quickly like staph aureus skin bacterium that you will encounter and the reason why stuff aureus is resistant to penicillin is because it produces an enzyme or like a pacman that chews up penicillin a penicillin is enzyme it takes about ten million years to evolve one of these enzymes so clearly that hasn't happened since we started using penicillin in the 1940s as a clinical therapy the reason why it was waiting and ready for us is that penicillin is a natural product it's been in the environment for millions and millions and millions of years and so bacteria in the environment have had plenty of time to evolve these mechanisms of resistance and then of course bacteria are very good at sharing their genetic information passing on these resistance mechanisms to other bacteria so if penicillin is found in your back garden penicillin resistant bacteria will also be found in your back garden if you go out gardening you're going to get those bacteria on your skin potentially from the soil and they're potentially going to share their resistance with your skin bacteria now you've got penicillin resistant skin bacteria ok so this is one of the reasons why antibiotic resistance emerged so quickly and still emerges so quickly because it's present in the environment of course the fact that we use penicillin will stimulate this process and the same with all antimicrobial you could draw this graph for pretty much NT any antibiotic that we use this is penicillin resistance it just shows that in countries that give out penicillin kind of a little bit like sweets where they use a lot they get a lot of resistance the faster sorry the more you use it the faster you lose it as they say countries like our Scandinavian colleagues where you have to be pretty much dead before they'll give you an antibiotic they don't use a lot and therefore they don't get a lot of resistance it's not rocket science really but by use an antibiotic what do we mean and I guess that's a bulk of what I'm going to say today's it's not just what you might use it's healthcare professionals it might be what's used around and about as in the environment it might not just be antibiotics that selects for this as well now Fleming discovered penicillin supposedly accidentally didn't really get involved in developing it into a drug but he still got the Nobel Prize anyway and everybody quotes this round about November antibiotic Awareness Week I see this on Twitter all the time you know Fleming he was so prescient he knew so much about resistance if we misuse antibiotics and we're going to cause problems of resistance and they try out this phrase if the man it's always a man it was ignorant anyway under doses himself then effectively that might cause resistance and he might postulate I think the court goes on say he's going to pass it on to his wife and she's going to die it's usually the way isn't it now of course pennant Lee Fleming said this without really knowing how antibiotic resistance evolves in fact Fleming said this without really knowing what antibiotic resistance means in fact clinicians today still argue about one Tabata resistance really means in terms of clinical outcome and so he was thinking about resistance in a very different way from the way certainly I think about resistance now and I'll explain that in a minute but this kind of idea that if we under dose patients if you're not quite getting enough antibiotic that dry resistance actually I think has led to some overuse of antimicrobials and this is one example in the veterinary profession so my wife's a small animal vet she runs her own practice she gets every week the vet record it's like the kind of BMJ of the vet world and nobody reads it in our house apart from me okay and you turn over and you get a page which says all we should prudently use unto microbials vets are very important and you turn the next page in there's a big advert for a new antimicrobial and you think okay what's going on and this is an example of the sort of mindset that vets are in they're really worried about this not giving enough antibiotic and they're particularly interested in this in the context of cats and maybe dogs that are different difficult to give tablets to if you ever try to give a tablet to a cat you know that you might lose your fingers and so they're worried about the idea that they're going to send the owner home with the tablets the owners going to give one get bit and then never give any more and that's terrible that's the worst thing you can do because you're under dosing the animal you're not completing the course so the drug companies picked up on this anxiety and so wouldn't it be nice if we could have a long-acting antimicrobial injection so they brought out this particular product which is safe ovation it's basically a third-generation careful aspirin this is a big-boy antibiotic but you inject it into your cat and now you can do it to dogs as well and it lasts in serum for about 14 days you don't have to worry about under dosing but actually most of the infection that this gets given for things like cat bye abscesses which probably don't need an antibiotic at all let's face it but if they do it might be a couple of days and that'll be it but you're committing as a clinician because of this anxiety I've wondered or soon to actually dosing the animal for 14 days with a third-generation cephalosporin okay which is critically important antimicrobial for human medicine that's rain isn't it yeah [Music] that provide boats for us to get out after it so this is the sort of thing that that can be can be worked towards and vets are using these drugs for convenience and it's called convenience the trade name of this thing okay now the reason why I think Fleming was wrong and the reason why people who are anxious about under docena sometimes wrong in terms of selection of antibiotic-resistant is because there's this perception that superbugs that antibiotic resistance is developed a bit like a giraffe developing a long neck so you imagine you think about the principle gradually over time the leaves just get a little bit higher on the tree and the neck just gets a little bit longer and gives us survival advantage and you could see how then if it's just slightly under dose so that the dose is just within reach the bacterium can evolve to be resistant to that and then you can go up and up and gradually eventually become resistant but superbugs are not giraffes they don't tend to evolve like some do and TB does streptococcus pneumoniae does gonorrhea does but most bacteria don't evolve resistance in this sequential mutation driven way they evolve resistance in a single hit because they share genetic information from environmental bacteria and from each other so it's effectively like a horse sticking on a giraffe costume just all of a sudden bang now they're resistant and now if you think about this concept that it's not sequential it's not about necessarily not quite given enough it's probably about giving antibiotic for too long because the longer you given the antibiotic the more chance you have of picking up one of these resistant organisms and so therefore when you're dosing your cat you're effectively create an account with a vacuum cleaner and I like showing this picture because it's a cat with a vacuum cleaner and it wouldn't that be good if you can't clean up after itself but anyway basically what you're doing I believe is you're because you're killing the normal bacterial flora with the antibiotic for 14 days before things start to calm down at least now your cat is potentially going and interacting with the environment and picking up antimicrobial resistant organisms from the which could replace its normal flora this is not an issue of therapeutic failure the cat by abscess is going to get better probably would have done anyway without the antibiotic but this is more about the issue of replacing normal bacteria in the gut of the cat and we were with towers and they're given antibiotics as well and so now you could have a I didn't couldn't find an actual photograph of a cow with a vacuum cleaners as good as I could do but humans are the same I would argue you know you've got this issue of interaction with the environment but animals perhaps interact with the environment more and so there's more propensity for them to pick up resistant organisms but we do know that when you dose patients with antibiotics they are therefore more lights have resistant organisms in in their normal flora so this is work done by Ashley Bryce is one of my postdocs on the projects I'm going to talk about this is work with Alistair he is a professor of primary care in Bristol it's a metro analysis publishing that this is just one antibiotic this is Ewan retract infection if you're given antibiotic then within a fortnight is six times more likely to be colonized with an antibiotic resistant organism this is trimethoprim it can do a similar analysis running takes almost a year before it goes back to one which is basically no difference from control so it takes a while for that effect and this is in the chat this is in Pediatrics okay it may be different in adults but in Pediatrics it certainly is quite pronounced and of course we know that interaction with the environment for humans just like animals is potentially going to affect us so this study came out last year which shows how if people travel to areas of the world where there's high levels of antibiotic resistant e.coli just in the environment they are quite likely to pick those up 34% of them and what's really interesting is that if those people happen to get ill law for some reason were given an antibiotic whilst they were on holiday they were much more likely to pick up so therefore this is this vacuum-cleaner effect I believe that there's being given the antibiotic they've then came home and they remain colonized for quite a long time potentially up to 12 months they stopped swabbing them after that time and they were still colonized and what's more passed it on to their household member the household members and now this the number star getting smaller because remember you've got to get 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