>> Tiffany Lee: Good afternoon Welcome back, everyone In this afternoon’s panels, we will start to look at food production systems and some of the challenges that we face with respect to antibiotic use, as Dr. Laxminarayan — got — yeah, okay — will [laughs] explain a growing world population might mean that we will be looking more toward nontraditional animal protein sources Panelists will discuss the sustainability of some of these systems and issues with antibiotic management So first up, we will have our own Ramanan Laxminarayan and he will — or, he is a director and senior fellow for the Center for Disease Dynamics, Economics, and Policy >> Ramanan Laxminarayan: Thank you, Tiffany, and thanks for the opportunity to speak here So if we were to look back at the past hundred years, I would say that one of the defining trends in what’s happening around the world is increase in demand for animal protein So next slide, please And this is — it’s been absolutely unprecedented If you look at total population around the world, it’s been growing steadily, as you all know So, you know, starting from the, you know, from the 1960s onwards, and at the current projection rates, we’re looking at a population that’s going to exceed about 10 billion people by the end of this century And that coupled with the idea that people are now looking to also increase their meat consumption has profound impacts on the demand for meat, and then of course on how we use antibiotics to raise that meat Next slide, please So the global population is expected to grow almost 50 percent since what we had in the year 2000, to 9 and a half billion by 2050 So that’s an enormous increase in a very short period of time Next slide, please And humans account for about 36 percent of the biomass of all mammals on the planet So this was an interesting study that was done in PNES a few years ago on the distribution of all global biomass around the planet Obviously, most of it is plants, but once you get into animals, you know, mammals account for a small proportion but of these — the humans account for 36 percent Domesticated livestock, mostly cows and pigs, account for 60 percent of all mammals, and wild mammals for only about 4 percent And if you take the biomass of poultry, that’s about three times higher than that of wild birds So essentially, humans and the food we consume, you know, constitutes the bulk of the mammal biomass on the planet Next slide, please And there’s some good work that’s happened by the food and agricultural organization, and researchers working on global distributions of cattle, pigs, chickens, and ducks, and these are some of those from the gridded livestock map of the world, which is now updated every year or two And it’s — these are projections, of course, what they’re based on is to look at the factors that would predict that there would be a certain concentration of animals in a particular pixel, so these are spatial maps, so the top left is the cattle As you can see, India — huge amount of cattle In fact, India exports a lot of cattle for food — for meat, mostly buffaloes And of course, you have a lot in South America as well, and then in parts of Africa Pigs — very clearly, China is the, you know, the leader over there, but that could have changed a little bit when they lost probably a third of their pigs to infections last year And then down below is chickens, and you can see India, China, huge concentrations of poultry, but also parts of the U.S. and parts of Brazil And then, you know, ducks is mostly a Southeast Asia kind of phenomenon We don’t have data from South America and Africa on ducks, but it’s mostly Southeast Asia Next slide, please So current protein demand for the 7 and a half — or 7.3 billion inhabitants of the world is about 202 million tons globally Since 2000, meat production has plateaued in high-income countries, but it’s been growing in the rest of the world — 68 percent, 64 percent, and 40 percent in Asia, Africa, and South America And that’s mostly because as people get wealthier, they would prefer to eat meat, not just once a year, but more like once a month, and then soon once a week, and soon every day of the week And that’s really the trajectory that you see across most of Southeast Asia Next slide, please And demand for poultry in both India and China is set to increase between two and sevenfold between 2020, 30 China, because it’s starting from a larger baseline per capita consumption, is already

pretty high, and then it’ll probably double before 2030 So these are all against baselines in 2000 India starts with a much lower baseline You know, contrary to what people think, India is not a vegetarian country It’s a largely meat-eating country, and the only reason people haven’t been eating meat so far is very simply because they couldn’t afford it, and now they’re about to be able to afford it, and so poultry consumption is going up substantially in India And of course you’ve got the population increases on the y-axis, which take you all up for that two to sevenfold increase Next slide, please Now this is actually data from Bloomberg, and Jason Gale, who’s here, was behind this story we saw on per capita pork consumption, which went up six-fold between 1975 and 2014, including the number of pigs produced And I’m sure most of you know that, you know, China has both far more pigs than the United States does and in fact, they also own some part of the swine industry in the United States So it’s a large part of not just Chinese economy but also culture And, you know, just to keep in mind, last year when there was a disease outbreak and a lot of pigs had to be killed, the projected compensation according to the New York Times in terms of compensation to farmers by local governments for the loss of their pigs was $3 trillion, $3 trillion And that was money that was to have been compensated back to local governments by the national government Now where the $3 trillion is gone is hard to believe, but that is the amount of composition, which also speaks to how central raising of pigs is in China Next slide, please So China now consumes half the world’s antibiotics, most of these are administered to animals, again from that same story And this is again — we’ve done this work which was published last year, which really shows, if you had to look for the one mammal on this planet that consumes most of the world’s antibiotics, it’s very specifically Chinese pigs Next slide And in more recent work, we’ve also looked at antibiotic consumption in aquaculture So that’s a very top fish, the dark blue And what we estimate isn’t — this is still unpublished work — that this is still pretty small compared to the consumption in terrestrial animals And the good news is that there is — there is greater awareness amongst this industry, and I’m sure we’ll hear more about it from Dr. Tlusty in terms of how this may not, you know, this may not take off at the same pace as it has in other — in terrestrial animals, but be that as it may, as the right-side charge — the figure shows, it doesn’t really matter where the antibiotics go in, because they�re going to spread everywhere It’s — we literally are like fish living in an ocean of bacteria and there’s no escaping them And as long as long as the bacteria in one place get access to antibiotics, they’re available everywhere So it’s — to some extent, it is irrelevant whether they’re going into, you know, the fish or the pigs or the cattle They’re all going to get back at drug-resistant infections anyway Next slide, please And this finally is that slide from Science, which really shows global antibiotic consumption, over 50,000 tons in China In fact, it’s more than the rest of the world put together by quite a long shot Next slide And the global consumption of food animals is about 131,000 tons and projected to reach about 200,000 tons by 2030 Next slide, please So that pretty much summarizes where we are with population growth, demand for animal protein, and product consumption Thank you >> Tiffany Lee: Thank you, Ramanan That’s fascinating And it sets us up very nicely for our next two panelists So Mr. Jason Gale is Features Editor for Bloomberg News, and please Jason, take it away Oh, turn your mic — there you go >> Jason Gale: There we go Thanks for the invitation to tell you about some of the work we’ve been doing at Bloomberg My slides will take you through the investigations my colleagues and I did into the use of antibiotics in food production, starting in India and ending in China with the integrated farming system you see represented on the right Next slide, please Our colleague in New Delhi approached me about five years ago about her interest in the use of antibiotics in what was the world’s fourth largest poultry meat market One of the two biggest suppliers of poultry meat in India had said on its website that it used no antibiotics in the raising of any of their broilers My colleague — my colleague was keen to test that claim, so she did what I don’t believe any journalist had done before She visited 14 large-scale farms in the Ranga Reddy District of the central state of Telangana

All of the farms were under contract to supply the major broiler and egg companies Essentially, the farmers followed the instructions of various field offices working for those companies in animal husbandry The journalist wasn’t familiar with the names of antibiotics, so I suggested she photograph everything You see in this slide a couple of examples, a logbook entry and a receipt Antibiotics were administered to chicks in their drinking water from day one Often the same antibiotics were used to sanitize sheds between flocks You see in this slide a woman wearing flip-flops behind a plastic container inside a chicken shed The bottle contained ciprofloxacin and enrofloxacin plus Colistin We learned that that was a particularly popular brew on these farms Fowl were also receiving neomycin, doxycycline, Tylosin, plus injections of gentamicin Disturbingly, we found that these drugs continued to be administered right up until just a few days before slaughter Gentamicin, as you’re probably aware, is heat-stable, so residues in the meat could remain active even after charbroiling The Indian government last year banned the use of Colistin for growth promotion Next slide, please I edited Natalie’s stories After they were published, Bloomberg decided to keep reporting on antimicrobial resistance, especially in the food chain This slide is probably familiar from [laughs] Ramanan’s presentation China was an obvious place to look next, given the massive use of antibiotics there And when you look at where the antibiotics go, you see food animals get the lion’s share of that Pigs get a big chunk Until African swine fever began devastating China’s pig herd; in mid-2018, it had half the world’s hogs Published data from a principal research scientist with the Chinese Academy of Sciences in Guangzhou showed an estimated 162,000 metric tons of antibiotics were used in China in 2013 Next slide, please Use of antibiotics had been rising because of increased domestic pork production That’s probably changed in the wake of African swine fever Next slide, please My interest was in the circulation of biologically active antibiotic residues from humans and animals in the environment and food systems, along with the associated antibiotic resistance genes The U.S. government imposed, more than a decade ago, restrictions on Chinese aquaculture imports because of residues I was interested in what was going on upstream in pigs after learning about traditional aquaculture practices in China and other parts of Asia and perhaps other regions of the world An average growing pig in China excretes 175 mg of antibiotics a day in its urine and feces Extrapolated across the national pig herd meant about 2460 tons of antibiotics are excreted by pigs annually, much of it undegraded The drugs and the antibiotic resistance genes spread through the environment, including waterways Traces of antibiotics have been found in the public water supplies of cities including Shanghai and Guangzhou, and when doctors tested the urine of 1,000 kids in Shanghai several years ago, they found 80 percent were positive for one or more antibiotics, including kids with no recent history of treatment Next slide, please So here’s the rub In China and many parts of Asia, farmers have recycled animal and sometimes human waste through fishponds for thousands of years It’s been a very successful and sustainable use of nutrients Here’s a video I took in Guangdong The pond contains tilapia that were jumping out of the water in excitement as solids were coming out of the pipe carrying the flush water from the pig pens It’s an example of the potential for emerging zoonoses, especially influenza Next slide, please The problem from an AMR perspective starts here This is a 20-sow piggery I visited in Guangzhou — in Guangdong, sorry I counted nine antibiotics in vials and containers on shelves, hanging in shopping bags and on top of trash piles These were just the ones that I could identify There could have been more A woman working at the local veterinary supply store came with us to the farm She told me that the farmer has to switch to a different antibiotic each month because of resistance, and as you can see, she’s built up quite a collection: benzylpenicillin, gentamicin, neomycin, streptomycin, sarafloxacin, ofloxacin, amoxicillin, sulfamonomethoxine, and ceftiofur Then, in the bag of feed she was using to raise her weaner pigs, were Colistin, Bacitracin,

and chlortetracycline This was before China banned the use of Colistin in livestock feed in November 2016 Traces of all of that end up in a pond raising 20,000 Mandarin fish for local and export markets The fishpond drains into a canal connected to a river system that empties into the Pearl River Delta on which sit the Chinese cities of Guangzhou, Shenzhen, Hong Kong, and Macau One study showed the estuary receives an estimated 193 tons of antibiotics a year Next slide, please China’s aquaculture production has expanded rapidly in recent decades Aquaculture represents roughly half the fish and seafood produced globally The FDA has said it’s the fastest growing segment of the global food economy China’s share of that is more than 60 percent, which means that roughly one in every three fish or seafood meals globally can be traced to a farm in China Not up to that slide yet [laughs] Shrimp, or prawns, as we call them in Australia, are a very lucrative part of that Production often takes place in the brackish water at the mouths of large rivers like the Pearl River Delta, which, as I just mentioned, receives more than half a ton a day of antibiotics So even if the shrimp aren’t being administered antibiotics directly, there’s a good chance they are being exposed through their environment When the FDA intensified monitoring of imported farm-raised seafood from China in 2006, it found a quarter of samples tested contained unapproved drug residues and unsafe food additives, some of them cancer-causing An import alert was applied to all farm-based shrimp and fish from China in June 2007 That allowed authorities to detain products until each shipment is proven to be untainted We believe some shrimp exporters in China found a workaround for that extra scrutiny A Bloomberg Businessweek investigation I led in 2016 found that shrimp in — from China were being fraudulently shipped to the U.S., where they were passed off as Malaysian shrimp We traced rejected shrimp shipments of Malaysian shrimp to farms like the one — the one [laughs] that you see on the right Yes, that’s a house, but import documents say it’s a shrimp farm A colleague and I drove hundreds of miles across Malaysia looking for what were meant to be shrimp farms and found they didn’t exist The organization issuing certificates of origin wasn’t verifying the information The government has tried to correct this, but the FDA now has an import alert on Malaysian aquaculture products I think this is a good example of how the media can be useful allies in exploring AMR threats and going to places and looking in corners to identify gaps and weaknesses Next slide, please So I’m going to end here Thanks for your attention >> Tiffany Lee: Thank you, Mr. Gale Next, we have Dr. Michael Tlusty, Associate Professor of Sustainability and Food Solutions at the School for the Environment, the University of Massachusetts, Boston >> Michael Tlusty: Thank you, and thank you for having me It’s been fascinating hearing everything that’s going on, and a lot of the discussions today have been leading to the water And it’s clear that what we’re putting into our bodies ultimately ends up in the environment in the water, and so there’s been a lot of work about sustainability and seafood systems And a lot of these sustainability initiatives actually influence antimicrobial use and disease of the animals, so we’re going to take you through that for a little bit One reason seafood is so important is that with this growing population, 20 percent of the world’s population depend on aquatic proteins for their main protein source So it’s critical, even though in the U.S., we eat on average — we have a record of 16.1 pounds of seafood per year And that’s an order of magnitude less than terrestrial animal protein, so we’re really not a seafood-consuming nation or a producing nation So in talking about seafood, we need to do some parsing out first because there’s over 2,500 species globally that are consumed as seafood products This includes ocean products, but also freshwater products, so it’s not — we’re not only talking about just ocean production We’re also talking about one of the last wild harvest — harvest of wild animals that we really have through fisheries There is likely some antibiotic use in that, but that’s such a minor component that we’re

going to focus on aquaculture Next slide So if we think about aquaculture, it is really just water farming, but again, we do so many different species and we do so many different production systems So beginning up on the top left, that’s oyster farming It happens everywhere around the world And interestingly, these can be just animals thrown out onto the bottom They can be put in bags and maintained a little bit better There’s a lot of animals that are hatchery-produced but we’re still collecting wild animals So just depends on where we are The interesting thing about aquaculture is that it provides an important ecosystem service and that these animals we’re not feeding They’re just filtering the phytoplankton out of the water, which is a great way to pick up all of the increased nitrogen that we’re dumping into our coastal waterways, okay? If you go to the top right, that’s almost the exact opposite This is offshore aquaculture off Hawaii It’s in 600 feet of water It’s a large cage You can see a person standing on it They’re raising a fish, a ciriola; it’s called compatche as its popular name These are fed fish Their bred in a hatchery It’s a very controlled system This is really what the U.S. needs to think about because if you look at our exclusive economic zone, which is 200 miles of the coast from land to 200 miles out, we have the largest exclusive economic zone of any country in the world, and so offshore aquaculture is going to be very important for our food future A lot of our offshore technology is actually coming from coastal aquaculture production, so down on the bottom right, we see salmon firms in Chile, and each one of those cages holds about 15,000 five-kilogram fish, so it’s a very high-production system It’s also very automated Those lines going between the cages? That’s actually pneumatic feeding tubes and they put pelleted feeds in those tubes, and there’s one person sitting on a feed barge with 5 tons of feed behind him, looking at a camera that’s looking in the cage, and they’re looking to see that the fish are feeding and he’s pressing a button to feed the fish So it’s a very mechanized product — process Down on the bottom left, that’s Lu’an in China, and so this is what Mr. Gale was just speaking about There aren’t pigs, obviously, on top of this, but you can see the immense density of the production system of tilapia here And you can actually see houses, so people live on these systems These are actual working farms And so it’s a variety of systems, and these are all the ones that are coastal and being — or in open water You know, the obvious solution is, well, why don’t we just take it out of the water and put it on land? Well, we do that We have pond aquaculture We also have aquaculture in buildings They are building three salmon farms on land in Maine There’s one in Miami that’s going to be 100,000 metric tons So we’re trying to get away from some of these things, but there’s trade-offs The minute you put something on land, you have a lot of greenhouse gas emissions through the cement, through the constant pumping of water Next slide And so if we look at — next slide Thank you So if we look at the U.S., again, we’re a minor producer, $1.5 billion in production But we’re the 16th largest aquaculture producer in the country So again, largest — exclusive economic zone and we’re just not producing there We primarily are a shellfish-producing country, so we do a lot of oysters and clams We do an equal amount of mussels and salmon, and we do some shrimp in Texas, but then in through the Midwest, we do a lot of pond production of shrimp And so again, these oysters and clams are — from a sustainability perspective, they’re really good because they’re unfed, they’re filter feeders, they’re helping clean the water, providing those ecosystem services But then again, it is a link to all of the things we are putting into the water Next slide And so if we look at the sustainability opportunities with antibiotic challenges, aquaculture’s been around We have Egyptian hieroglyphics showing tilapia production So it’s been around for long time At scale, it’s relatively new It really started in the late ’80s and into the ’90s, where we were doing concentrated animal production for developed world markets So we’re still trying to figure out what are the best ways to design systems, but then we don’t know what all the challenges are And when you come up with challenges in animal production, you start — you start having disease Again, there’s many species in aquaculture There’s about 600 dominant species, but 44 of those are about 90 percent of all of our

production And so we’re still figuring out what are the best species to actually be eating In the United States, we eat a lot of shrimp and salmon, which are produced in aquaculture Globally, carp and Japanese oysters are the two dominant animals that are farmed So when we think about aquaculture in the U.S., we’re not even eating the way the world is producing food And again, the issue is with new species, there is disease challenges, and we don’t know what to do And many of them are invertebrates and their immune system is completely different, so a lot of times we’re even flying blind on that Many of the systems are open and so if you put antibiotics in, they’re immediately diffusing into the environment That’s a problem Or they’re open and anything coming in from an external source can actually contaminate the product And so that’s a problem And there’s work around siting and carrying capacity and making sure things are put appropriately Another benefit is when you think about shrimp and oysters, an oyster — every time a female oyster releases gametes, she releases 2 million eggs The production of — we don’t have to maintain one animal or 10 animals or — one animal for every 10 or one animal for one, as we do in terrestrial systems We can have a very small allocation towards broodstock So that’s good, but it’s also a challenge because we have tiny, tiny babies and they really get hammered by bacteria Just — it’s terrible And so there’s a lot of sanitation in hatchery systems, and a lot of that likely contains antibiotics which people don’t — it’s probably just an undiscussed aspect of it And then there’s a lot of small farmers Vietnam alone has 500,000 shrimp farmers When you have small farmers in developing countries, a lot of them are illiterate and they don’t understand what’s going on, and somebody will hand them a powder and say this will help your animals grow, and they say thank you And a lot of times those contain antibiotics, but not even at a reasonable level They’re all cut and they’re all diffuse and it can lead — it can lead to problems Next slide So I’m sure you’ve all seen this [unintelligible] Venn diagram of disease and it’s caused by having a susceptible host with a suitable pathogen in a permissive environment So if you focus on the environment when we talk about sustainability — next slide — really, sustainability is balancing making sure we have the integrity of the environment while balancing the socioeconomic needs of the local people So having that, that eventually turned into the triple P, people, plan, and profit model But in its original implementation, it’s really balancing socioeconomic needs with the environment If we combine those two Venn diagrams, focused on keeping the environment constant — next slide — really what we see is that you can have sustainability, which is where you have environmental integrity with the socioeconomic benefits, and you’re farming animals in a way that doesn’t have health challenges But reality is we will always have health challenges in any sort of animal production And that’s where we can get management for sustainability And this is very critical, because we need to have these tools where we can manage for sustainability, but yet at the same time — we heard yesterday, we’ve heard some today — when you start pushing farmers, you know, every farmer wants to take good care of their stock Every farmer says they take good care of their stock When push comes to shove, and they need to make money, they will cut a corner to make money And so this is where we need to think about this manage for sustainability and what are we doing Because, again, the minute it behooves them economically, they will — they will cut a corner And then that’s where animal health, antibiotic sustainability all start to fall apart Next slide So aquaculture is new, but there’s a — there’s a very concerted seafood sustainability movement You know, almost every restaurant has sustainable seafood Every market has sustainable seafood And so it’s been asked to do in 20 years what it’s taken terrestrial agriculture 100 years to do, and get up to these super strict code of ethics and practice But really, again, going back to Captain Cousteau, we really need to think about farming the oceans as we do farm the land

Thank you >> Tiffany Lee: Very good Thank you, Dr. Tlusty All right We will open it up for questions, and Dr Blaser has already got one >> Martin Blaser: I want to thank our three panelists for a really interesting session My question is to both Ramanan and to Mr Jason Gale It’s about antibiotic use in both China and India The paper that you referred to, I think both of you referred to the Guo paper from 2015, but you didn’t tell everything that was in that paper, because what Guo estimated is that 162,000 tons are used in China annually, but then there was another 80,000 or more tons exported So China’s producing 250,000 tons annually of antibiotics The amount that they export is five times as much as the U.S. produces So I guess the first question about that is how accurate is this, and do we have any other estimates? And the second thing is, obviously, they’re undercounting in India And how much are they undercounting? How — what does it look — what are the estimates for antibiotic production in India? So we can deal with both of them >> Ramanan Laxminarayan: So I was just going to say that our Science paper is obviously [unintelligible] but because we’re calculating that from the ground up in terms of milligrams per PCU, multiplying it by the number, you know, by the kilograms of animal, and that’s how we get at our estimates So the 130,000 tons is obviously much — that’s the global estimate That’s obviously lower than what quotes, you know, that they are citing This is clearly an area where we’re all in a — you know, plus or minus 50,000 [laughs] tons region, which is not a great place to be, in general But I would say that the conference intervals are — the world is probably using somewhere between 150,000 and 300,000 tons It’s as wide as that in terms of what we do know We don’t know if it’s 150 or if, you know, it’s 300,000 tons in animals But keep in mind that a lot of what China’s exporting is also coming into India, also going into Africa, so these are not separate China is producing them, but these are all countering what the rest of the world really uses But that’s the order of magnitude of what we’re using And if you compare that with human use, roughly about two thirds to about 70 percent is in the animal sector when you compare it with the data from humans, which I think is a more reliable number that we have, than what we know about the animal side >> Jason Gale: I think Ramanan covered it [laughs] pretty well Thanks >> Tiffany Lee: Okay Other questions? >> Michael Apley: I’ll do one, Tiffany >> Tiffany Lee: Mike? >> Michael Apley: So in the — in the use you encountered, what were the regulatory structures around that? Was there attempted regulation? Was there any requirement for authorization? >> Jason Gale: I didn’t observe any regulatory frameworks This was a good four years ago It may have changed since then, but it was very apparent to me that anyone could go into a veterinary supply store in this part of Guangdong where I was visiting and buy whatever they wanted And I definitely saw a large array of antibiotics >> Tiffany Lee: Thank you Dr. King? >> Lonnie King: So Dr. Tlusty, just maybe a question on — talking about antibiotic use in aquaculture and fish production What’s your experience and what’s being done in infection prevention, and how can that be tied into, you know, more in stewardship and using less antibiotics So do you have any examples of infection prevention in this part of the industry? >> Michael Tlusty: Yeah, in salmon, which — salmon is very vertically integrated, and it’s estimated that 18 companies control about 80 percent of salmon production And in there, you also have a larger fry to work with, and so they have vaccine programs And so Norway’s been very effective, where the use of antibiotics in salmon production in Norway has really gone — I don’t want to say to zero, but functionally to zero But if you contrast that with Chile, antibiotic use is increasing And again, part of it is Chile is still considered a country that’s developing their aquaculture production

They continue to move further and further south into the 11th and 12th regions, and as every time you kind of try to set up in a new area, there’s a — there’s a learning curve It confuses me, because a lot of Norwegian companies own what’s going on in Chile, so why can’t they figure it all out the same? So in salmon, good management and stewardship has led to decreased antibiotic usage In the next session, Sebastian is going to talk about certification, and a lot of certification programs are working towards something called zonal or area management So when you — if you think back to the slide I put up of the salmon firms as opposed to the tilapia production in China, zone management looks at the water body itself And so it’s not only looking at the impact of the farm, but what’s the cumulative impact of all the farms within a specific area And with that, a lot of — one of the key parameters of area management is coordinated disease treatment So if one farm has a problem, you make sure everybody’s treating at the same time to limit the impact and the spread of that disease So area management is something that a lot of aquaculture certifications are working on, and so — and so that’s one of the positive examples coming out >> Tiffany Lee: Any other questions from the group? I have a question for Dr. Tlusky [sic] — Tlusty, sorry So you mentioned the short time span that, you know, aquaculture has had to kind of develop compared to terrestrial animal systems >> Michael Tlusty: [affirmative] >> Tiffany Lee: When you look at antimicrobial stewardship either programs or regulations, in particular in the United States, but in other countries, are those stewardship programs really driven by regulation, or are they driven by industry? >> Michael Tlusty: You’re referring to, like, the certification programs as being the stewardship programs? >> Tiffany Lee: Any kind of stewardship >> Michael Tlusty: Yeah, any — okay So if you think about the certification, that was really driven by a distrust by western and global north markets, where we knew there was product coming in from countries, and we didn’t trust the country regulation So independent bodies went in and said we need to ensure that a code of practices is being implemented And over time, a lot of those through-market pressures have said a no antibiotic policy So the Aquaculture Stewardship Council, which is a little bit more predominant in Europe, but they have a no antibiotic policy for any of — anything being certified That being said, one of the bacteria that affects aquaculture the most — and I’m kind of surprised I haven’t heard it over the last two days — is vibrio, and especially vibrio parahaemolyticus in 2013 affected Thai shrimp production to the point of where you could see a global downturn in global shrimp production And it’s something they weren’t monitoring, they didn’t know it was happening, and they only realized it once everybody recorded what happened that year and they said, whoa, we’re down 30 percent So there’s no sentinel monitoring And part of it is your farming animals that you never see, you know? Oysters — sometimes when the tide goes out, you get to see your animals But for the most part you don’t see your animals until you go into harvest And that presents just another challenge in terms of disease sentinel work >> Tiffany Lee: Thank you We have Locke Karriker? >> Locke Karriker: Yeah, thank you for these presentations I think they were really informative This is for Dr. Laxminarayan Do you think, given China’s role as a producer of antibiotics and its large chunk of consumption in the pig population, it’s now gone with ASF and doesn’t appear to be regenerating very quick — are those antibiotics, you think, more likely to be exported to countries with modernizing food production systems and lower regulation elsewhere in the globe, or do you think they’ll be consumed by other species in China or — what you think happens with those antibiotics? >> Ramanan Laxminarayan: You know, that’s a great question It did occur to me, and I — frankly, I don’t know if Jason knows the answer to this I would imagine that the place to look is to see if the price of antibiotics has dropped, because the supply has stayed the same, and the demand has just dropped tremendously So, no, we don’t know the answer to this, and they can’t be anywhere good that all those

antibiotics are going to, except probably a storage space somewhere >> Locke Karriker: Right I think it — I think the risk is that it promotes poor practices elsewhere on the globe, potentially, so >> Ramanan Laxminarayan: Possibly Probably a story for Bloomberg >> Locke Karriker: Thank you >> Tiffany Lee: Okay Dr. Plummer >> Paul Plummer: So thank you for those presentations They were enlightening I’m particularly interested in this open water aquaculture system and what level of understanding — just some — I realize this is a big question, but in terms of understanding how currents and tides and all of that affect the pharmacology of the drug and, you know, the distribution of that drug, and how much is known about that, or is it kind of an empiric, put this much in this size cage, and we don’t know how all of that’s impacting in? I’m sure there are some signs there, but just trying to get a sense of how much we know about that >> Michael Tlusty: We actually know a lot about currents and particle flow around cages, because I alluded to carrying capacity, and a lot of that is done with modeling And so if you look, you know, one of the concerns is that as excess feed or feces leave the cage, you don’t want it to hit the bottom and bury and become anoxic and have problems So we know a lot about particle flow and deposition around the cage sites That could be easily adopted for chemotherapeutic and some antibiotics You know, is it — is it soluble? Is it particulate? How is it moving? You could put those in I would — I would hazard a guess and say nobody’s really thinking about using depositional models to look at how antibiotics are moving around cages So the models exist, but it hasn’t been applied in that way But that’s a great suggestion I’ll work on it >> Tiffany Lee: Okay Very good Any other questions from the council? Great If not, we are ahead of schedule Jomana? >> Jomana Musmar: Thank you so much We’re just going to keep rolling through We’re going to forgo break, folks, and try to finish early today, so I’ll defer to Dr Aileen Marty Unfortunately, Dr. Alice Johnson could not join us today She’s feeling a little under So Aileen Marty’s been kind enough to step in as moderator >> Aileen Marty: Welcome Let’s let the new speakers sit down for a second Just to let you know that our final panel of the day will continue some of the themes of the previous panel, exploring deeper aspects of seafood production, and Dr. David White, the Associate Dean for Research, Department of Agricultural Research at the University of Tennessee, will introduce the topic with an overview of aquaculture systems, and we will then hear about a success story for encouraging antibiotic-free seafood, followed by an update on surveillance activities through the NARMS program Welcome, Dr. White >> David White: Good afternoon and thank you for the invitation to present I guess if we had done this properly, we would have had this session yesterday with Ash Wednesday That would have made a nice alignment with fish in that I’m going to give a little bit of an overview It’s kind of going to be a little duplicative of what we’ve heard earlier from our really good speakers Up on that top left, as you can see, that’s actually the hieroglyph that was mentioned from one of the Egyptian tombs, and it shows a picture of farming tilapia, but it even goes back further than that I think the first documentation of aquaculture goes back to Chinese over 4,000 years ago, where they were raising carps So it’s been a long time, but as Dr. Tlusty mentioned, the scaling up has happened over, like, the last 50 to 70 years First, I need to disclose I am an employee of the University of Tennessee, and I have been a past consultant for the veterinary consultant group Next slide, please So in terms of aquaculture, as you heard, it is the fastest growing food production sector globally, and now provides half of all fish consumed by humans Global fish production in 2016 reached an all-time high of 171 million tons I mean, just think about that That is phenomenal Eighty-eight percent of that is direct human consumption, and of that 171, aquaculture accounted for 80 million tons, and I’m going to show you the distinction between what that means The value of fisheries and aquaculture is estimated at $362 billion Again, 232 of that from aquaculture And globally, per capita food fish consumption grew from 9 kilograms in 1961 to 20.2 kilograms in 2015 and it is growing So that’s globally As you heard earlier, in the United States it’s a little bit lower than that

And we need to remember that this is also food for animals It’s not just food for humans There’s also fish meal that goes back, animal feeds, and so forth Our pets are eating fish meal, that goes into that So there’s — a lot of the fish being produced is also for animal consumption as well Next slide, please In terms of aquaculture, aquatic products for direct and indirect human consumption have two origins Looking through the literature, this may change a little bit in terms of the lexicon, but it’s either through capture fisheries and aquaculture — and capture fisheries refers to the catching, processing, and marketing of wild fish or shellfish — whereas aquaculture is the purposeful breeding, rearing, and harvesting of fish, shellfish, including algae and other organisms in all types of water environments And those two main types can be either marine, where you have net pens in the water or tanks on land, or freshwater, which is ponds or other man-made systems And these pictures — Sebastian may recognize these These are actually from Marshall Cove mussel farm in Maine So those are mussel ropes They’re like 40 feet long and the mussels grow on that and they pull them up and harvest It’s — some great YouTube videos, if you’re interested It’s fascinating Next slide, please In terms of the production, this is data from NOAA from 2016 As we’ve heard earlier, Asia produces 89 percent of the global aquaculture production of fish, crustaceans, and mollusks The top five countries on the left highlighted in the red bar — obviously we’ve heard this, too — China, India, Indonesia, Vietnam, and Bangladesh We are 16th in that, but we are the leading global importer of fish and fishery products, and recent estimates are nearly 90 percent of what we eat comes from somewhere else Ninety percent Even some of that is from here, but is exported overseas and then returned back to this country It’s cheaper that way to do that, if you can believe that Next slide, please You saw this slide in terms — from earlier, but just to go through it, the estimated freshwater plus Marine U.S. aquaculture production was 633 million pounds, with a value of $1.5 billion Freshwater production is primarily catfish, crawfish, and trout The top U.S. Marine aquaculture species are oysters, clams, and Atlantic salmon Again, as you heard from Dr. Tlusty, the U.S per capita consumption was 16 pounds, and its estimated we spend about $100 billion per year This is from 2016 Next slide, please In terms of the technologies for aquaculture rearing, they’re very broad in scope, but there’s primarily five major systems One is hatcheries, which is that top picture It’s a mix of a laboratory and a farm, where fish and shellfish can be spawned, hatched, and cared for The next one below is pond culture This is what — you’ve seen pictures of this before, where we have one or many earthen ponds are used to culture some freshwater species We have cage cultures, which are enclosed Cages are submerged in aquatic environments There are careful protocols and monitoring needed to help minimize potential interactions with the environment when you have these cage cultures The bottom left, you can have recirculating systems, and these are fish, shellfish, and plant life are raised in closed loop production systems that continuously filter and recycle water and waste You can tell that obviously has an energy footprint in the recirculating systems And lastly, I think what the goal is, is something called an integrated, multi-trophic aquaculture system, where you have several species raised together in a way that allows one species’ byproducts to be recycled as feed for another, so it’s a very holistic way of harvesting or growing multiple species linked together Next slide, please Obviously, like terrestrial farming, disease and health management is the primary challenge for successful aquaculture Like any other type of farming, it has impacts on surrounding environments The most significant issue is maintaining animal health and controlling disease An FAO estimates 40 percent of losses of aquaculture are due to controlling disease That’s pretty big Numerous bacterial, mycotic, viral, and parasitic diseases unfortunately impact aquatic production These include a lot of bacterial pathogens, including Aeromonas, Pseudomonas, Vibrio that was mentioned, Photobacterium, Edwardsiella, Flavobacterium, Streptococcus, and Mycobacterium I’m sure several of those species this committee is not familiar with, and that’s part of the problem, is that we don’t have much information on these pathogens and what they do And much like terrestrial farming, due to the nature of dense populations, there is an increased reliance sometimes on antimicrobials to control disease And on the right, the OIE, the World Health Animal Organization, does have principles

for responsible, prudent use of antimicrobial agents in aquatic animals, and that’s something you can get to online So there is international principles for responsible use of antimicrobials in aquaculture Next slide, please So the OIE also has a listing of reportable aquatic diseases that require timely notification to prevent transboundary spread And I don’t intend you to look at everything here, but this is just to show you there are a lot of diseases, frankly, in the different species that are out there So there is a lot of opportunity in aquaculture to provide greater protein, but there’s also a lot of diseases that have to be managed And one of the tools that needs to be used is antimicrobials and also maybe vaccines, if we can get into that a little bit more Next slide, please So for the United States, currently there are four approved antimicrobials, but I believe three that are marketed: Florfenicol, which is a fluorinated fenicol, oxytetracycline, and ormetoprim sulfa, and these are approved as medicated feeds And again, the bacterium that these antimicrobials are approved for are ones that we don’t typically see in any, obviously, healthcare setting: Edwardsiella, Flavobacterium, Aeromonas These are pathogens that impact, you know, catfish and salmonids and so forth So there’s only a few researchers working on this, frankly, and that’s part of our problem is, we don’t have a lot of scientists across the globe working on these particular seafood products — I shouldn’t say products, but the actual commodity versus the pathogens as well, because they all grow at different temperatures, they have different pathogenesis mechanisms, and — as well as the antimicrobial resistance mechanisms Next slide, please So to wrap up, I’m going to say the biggest challenge is disease and health management That top right picture may be tough to see, but it just shows where a lot of the seafood is coming into the United States So we are at the whim of those countries in particular, as was mentioned with Chile You know, what is happening in Chile in terms of what compounds are being used in their aquaculture settings It’s a good question They don’t have the regulation that we do in United States So there is some question about what’s being used As aquaculture continues to expand, the risk of significant disease outbreaks does become a major concern globally I think there’s a pressing need for investment in aquatic health and greater access to disease management tools This includes more data on pathogens as well as the host species data Surveillance data, which is lacking, which is — I’m glad to hear later on Dr. McDermott’s going to be talking about a pilot program norms We need more vaccines to prevent antimicrobial use and to make sure there is stewardship, but there are some innate challenges to vaccines In particular, shrimp do not have an innate immune system, I found out, so they don’t produce antibodies So [laughs] you’ve got to do something else to stimulate their immune response to, you know, to allow them to survive in the presence of pathogens In terms of antimicrobials, there are stewardship programs out there, but in terms of enforcement or compliance with those, I think that depends on country Rapid diagnostics are desperately needed so that we can quickly detect these pathogens and then determine, you know, if antimicrobial therapy is needed And, of course, biosecurity measures And I think also you’re going to see the need for development of sustainable aquaculture guidelines — which we may here also as well — are happening globally So with that, I thank you very much, and I appreciate it >> Aileen Marty: Thank you for that very informative and somewhat frightening — [laughter] — presentation [laughs] Our next speaker is Sebastian Belle He’s going to be talking to us about certification standards for antibiotic free seafood, a very interesting topic He’s the Executive Director of Maine’s Aquaculture Association Welcome, Mr. Belle >> Sebastian Belle: Thank you very much I’m going to start by saying I’m the least qualified person you are going to hear from in the last two days I am not an academic, I am not a researcher, I am not a clinical practitioner I am a fish farmer who is washed up on shore [laughter] And so what I want to share with you a little bit is what we have done in Maine and how we have quite unintentionally gone at the use and the challenges that antibiotic use present in a food production system We did not go into this intentionally at the beginning, but we have come out at the end of a pipeline that we’re actually quite proud of Next slide, please You’ve heard a lot from other, much better qualified people than I have with regard to aquaculture, but I just want to graphically put this up on the screen We produce very little of what we consume in terms of seafood in this country And obviously, I represent domestic farmers

Next slide But globally, aquaculture is the fastest-growing food production system in the world Roughly 8 percent per year annually over the last 20 years, and it has disease challenges The World Bank estimates that roughly $6 billion a year are lost in the aquaculture sector as a result of disease We are growing new animals using new methods in new places, and that presents challenges We are learning as we are going I’m not going to lie to anybody We’ve been doing this for a relatively short period time in the modern world, and we are learning by iteration Next slide The context for me as a farmer is the balance between the One Health approach and the Global Food Challenge that we are facing We need to double our food production by 2050 if we are going to continue to feed the world the way we do now And frankly, the way we feed the world now, we don’t do a very good job There are roughly a billion people a year who are in a food insecurity position So we’re not doing a great job now If you add 2 and a half billion people or 3 and a half billion people to the equation, by 2050, we are going to be increasingly challenged And the fact that we have to grow double the amount of food in that time period in my children’s lifespan is a real challenge Next slide Aquatic animals are different than terrestrial animals, and this is something which is often misunderstood in the public They are cold-blooded, so just for the record, to go on the record, antibiotics, antimicrobials do not work as growth promoters in aquatic animals, with possibly one exception to my knowledge And so this whole concern about using antibiotics prophylactically to promote growth is kind of irrelevant for aquaculture, although we have been painted by the same brush in some instances There is prophylactic use of antibiotics in aquaculture, and that’s not a good thing And it’s used oftentimes in other countries where there is not the disease diagnosis infrastructure to be able to identify what the pathogens are that the farmer is facing, and then give the farmer good advice about how to deal with that In the United States, as has been alluded to earlier, we have basically three antimicrobials that are in our toolbox, and that, frankly, increases the risk of resistance — doesn’t decrease it Because we have limited ability to shift between antimicrobials as we’re going through the production cycle Our knowledge of pathogens in the aquaculture world is much more limited than in human health or in terrestrial animals We are still very early on in the understanding of what the pathogens are that we face as farmers And our ability to administer antimicrobials is also significantly limited We are working in an aquatic environment, and we can’t do things that some terrestrial farmers could do from a pure application perspective And finally, the entry of health professionals into aquaculture is relatively new The veterinary community has only been involved in the aquaculture sector for roughly 15 years, and we have had pathologists involved in aquaculture for maybe 40 or 50 years So from a health professional point of view, that profession has a long way to go in terms of learning and developing techniques to be able to help us as farmers And finally, our husbandry methods are also new We have really only been — although you talk about going back to the Greeks and the Egyptians and the Chinese, we’ve only been growing animals in aquaculture in modern terms for roughly 100 years Next slide, please So for any pathogen that we face as farmers, each pathogen is different, and the balance between protecting public health and animal stewardship changes depending on the pathogen you’re talking about and the tools that you have So in the case of, for example, infectious salmon anemia, which is a pathogen that we have dealt with in Maine, there are no antimicrobials that work for that pathogen It’s a virus, and we have to manage that disease completely using nonchemical methods In the case of some bacteria that’s attacking the Chilean salmon industry, it is a bacteria, although antimicrobials do work, but it is highly resistant to application of antimicrobials And so you see the antimicrobial use in Chile the highest use that we know of, at least documented in the world in finfish aquaculture at this stage of the game Next slide So in my part of the world, we have shifted from a chemical approach to a nonchemical approach And there’s a slide that didn’t make it into the presentation I think the committee has that slide but I’ll just go through our chronology

We started in 1992 with some comprehensive fish health surveillance regulations And we, as an industry, lobbied for those They are some of the strictest surveillance regulations in the world That was just because we didn’t know what was out there and we needed to understand that And we needed it to be mandatory across the sector We, then, in 1994, were the first fish farmers in the world to go to third-party biosecurity audits This was an unannounced visit by a veterinarian came on the farm and audited that farm in 160 areas on the farm And that veterinarian gave that farm a score The veterinarian came out of the poultry industry, Dr. Mike Opitz And that score was put up on our annual general meeting at the Growers Association So, all the farms had their score put up on the annual general meeting And you did not want to be the farm with the worst score That was over and above all the regulations that were in place at that time In 1999, we put in place pathogen-specific action plans These were pre-agreed plans that triggered actions by the growers in response to a positive disease testing So, one positive disease hit from a sample would trigger the initiation of the action plan And all farmers had to comply with that action plan In 2001, we were some of the first farmers to begin to do area management programs This was where all the farms in a bay signed a legally-binding document between the farms to manage to the same level from a biosecurity point of view And we had farmers sue each other non-compliance of those agreements And, again, that was non-regulatory That was the farmers working together Included in those area management plans were site rotation and fallowing, which really changed our world from an antibiotic use point of view When we went to site rotation and fallowing, all-in/all-out management, the use of antibiotics in Maine decreased dramatically And finally, in 2004, we went to full, formal farm and area biosecurity plans Those included expanded surveillance plans and cooperative communication plans between the farmers where were men — mandated communication between farms if you had a suspected disease or pathogen detection, not a confirmed pathogen detection One of the things to understand about aquatic animal health is that the definition of a positive case is still fluid We have a lot of different detection methods out there And some of them result in a high degree of false positives And so, we are learning, as we go, that we need secondary confirmatory tests in order to confirm the positive tests And then, finally, in 2016 — next slide — we began to go to — actually, next slide; skip over this slide — we began to go to these large international certification programs There are a bunch of different logos up there These are now kind of the state-of-the-art, internationally, where third-party, private organizations come in, and audit your farm, and certify them to a whole series of standards These are, again, over and above the regulatory requirements in the individual company that they’re certifying in And this is being driven by the buyer community So, Whole Foods, Walmart, Costco, Legal Sea Foods: they are all requiring that you are certified by one of these certification programs And as Dr. Tlusty alluded to earlier, many of these programs are driving towards a zero antibiotic use or a prudent use antibiotic use model, which is based on both the OIE and WHO model The one challenge — next slide, please — and this is my last slide — is that the coverage of these international certification programs in the seafood sector is relatively small And so, less than 2 percent of world production, currently, is certified by these international programs And if you look at how many farms are under assessment globally, roughly another 1 percent of the global production is under assessment currently What is interesting is the next level down below these certification programs, which are what are, really, a green rating program, which are largely carried out by environmental NGOs, people like New England Aquarium — Dr Tlusty used to work for them — Monterey Bay Aquarium You may have heard of their rating system Those programs include another roughly 52 percent of the world’s supply

Many of those programs have a review of antibiotic use and stewardship in them Most of those programs are not a — are not programs that require antibiotic-free systems Last slide So, what I would like to do, as a farmer, is make a plea to you, as a committee, that don’t forget that we, as farmers, have to balance two things We have to balance our responsibility for the animal welfare stewardship of the animals that we are responsible for with the public trust stewardship of human health and human welfare And that is not always easy to do There are times when we choose to kill animals instead of medicating them And that is a hard choice for farmers to make I will tell you that farmers go every day on the farm and they personally vest themselves in the animals they are growing They don’t name them, individually But they do care about them And to make the decision to kill animals because you have a positive disease result, and you don’t believe that you have a health-management tool available to you, is a heart-wrenching decision and a financially costly decision So, please don’t forget that in your equations And thank you very much >> Aileen Marty: Thank you, Mr. Belle That was incredibly informative and very valuable perspective Our last speaker is Patrick McDermott He’s the director of the National Antimicrobial Resistance Monitoring System for the U.S Food and Drug Administration Center for Veterinary Medicine He will be talking to us about National Antimicrobial Resistance Monitoring System for seafood pilot program Thank you, and welcome >> Patrick McDermott: Thank you Thank you very much Thank you to the council for the opportunity to share with you today some of the work we’re doing in NARMS to, say, move beyond our traditional surveillance activities, looking at terrestrial animals and their drive meats, and to look at, now, into seafood products, as well Next slide, please I should point out, NARMS, if you don’t know it, it’s an interagency collaboration of FDA, CDC, and USDA It’s been around since 1996 It’s a very successful partnership We were recently reviewed by a subcommittee of the FDA Science Board Some of you in this room are part of that subcommittee where recommendations were made on how NARMS should seek to transform itself to accord more fully with the One Health model of surveillance And part of that includes, you know, looking at an environmental water component We’ve heard a lot of talk today about water We’ve got some really interesting data in our early foray into environmental testing of surface waters, working with EPA, who’s — who has categorized rivers and streams by — on a grading of impact from built, human, and agricultural environments So, we have an opportunity to combine the microbiome data with the — with that classification system in EPA and come up with some sort of grading of risks associated with different points in the water stream So, we’re excited about how that’s evolving And maybe that’s something we could present at a later date Also accord with the One Health design, we have added companion animal and food animal pathogen testing This is to complete the third leg of the One Health model, which is to be concerned and to share — generate valid information and share it on resistance in animal pathogens Our recent NARMS report had the first data from companion animal surveillance We’re working closely with USDA and the National Animal Health Laboratory Network to try to get data on food animal pathogens, as well, and try to add value to that stakeholder group from this national testing Part of the way we’ve conceived of it, though, all along, is not just the One Health model, but to make sure that we are getting some information on all the environments in which antibiotics are approved in the production of food products And so, seafood is one that we had discussed a long time but weren’t in a good position to pursue until recently Obviously, we’ve heard how much is imported and that antibiotics are used in seafood production in aquaculture So, it certainly presents an opportunity for resistance to enter into the U.S Dr. White shared with us the three main antibiotics that are approved in the United States: fluor-fenicol, oxytetracycline, and sulfadimethoxine or ormetoprim We began a serious discussion about how we should be looking for resistance to these and other medically relevant antibiotics back as far as 2016, where we started discussions first with our Canadian colleagues at CPARS, but also CDC, USDA, FDA’s Center for Food Safety, and our drug-approving teams to try to come up with a rational design that would present a best distribution of resources across all the different array of activities in NARMS

that would give us a good return on investment and a good assessment of what resistance might be present in imported — largely imported seafood products We decided, at the end of these discussions, to focus on salmon, shrimp, and tilapia, as we’ve heard those — well, first, other than canned tuna, they’re the top three most consumed seafoods in the U.S But they’re also, all three, raised in aquaculture systems Next slide, please So, the data in the literature were somewhat scattershot on what we might expect There were some targeted studies, as is often the case, but not a large — but not many largescale studies that gave us an indication of what the best target organisms are And there’s a lot of complexities associated with monitoring seafood products that don’t apply in terrestrial animals, such as the fact that these are cold-water animals and they’re usually have a microbiota that is more cold-loving, let’s say, than the mesophilic organisms that normally cause human infection So, we began with the discussions with others who had some experience in this But we also thought we should look using metagenomic approaches to see what the taxonomic structure looked like in seafood products coming into the U.S., and to use that information in the study design So, what this slide shows is that if looking at salmonella, shrimp, and tilapia, we compared, basically, rinses of the meat products, which is times zero there in the slide, with samples that had been incubated for 24 hours, following more traditional methods And you can see how the — sort of the phylogenomic profile changes when you incubate these overnight So, for example, looking at the salmon on the left had so many pseudomonas comprised the taxonomic profile there And those were sort of taken over by Aeromonas after culturing So, this simply represents another layer of complexity in the study design We’re really interested in the resistance genes and the resistome And we’re obviously losing the native state of that sample when we culture it in traditional ways to grow microorganisms So, I think the lesson here, and the point here, is that we’re going to take a two-pronged approach to this using both standard, traditional microbiological methods combined with metagenomic methods to try to get the deepest picture we can of the microbial status of these main aquaculture products Next slide, please So, in our discussions and based on the metagenomic screening, we came up with a list of target organisms to pursue a traditional culture-based methods And they’re listed here in some reasons for why we thought they might be included in this pilot study So, vibrio and salmonella are the main microbial causes of foodborne illness from seafood — fish and seafood products And so, we set out to look for both salmonella and vibrio We included Aeromonas It’s ubiquitous in the aquaculture environment It is an opportunistic human pathogen, as well as a fish pathogen Enterococcus is a fecal indicator and a reflector of gram — of drugs with gram-positive activity And we also thought, given the importance of carbapenem resistance, that that ought to be included, as well And we discussed staph aureus as being part of it, and pseudomonas, as well Next slide, please So, the 2019 project that we began last year with eight states These are some of the partners we have in our retail meat-testing in NARMS and worked on an arrangement with them together Fresh and frozen shrimp and skin-on salmon from retail outlets across the year And then, midyear, we added tilapia to the sampling design, as well So, each state, every month, was getting eight samples, which gave us about 768 samples for the pilot year, which gives us about 80 to 85 confidence in a situation with a 50 percent prevalence And I should add that in addition to this we’ve been working with USDA FSIS to look at Siluriformes, basically catfish, which are a major freshwater pond fish raised in the United States And so, at the same time, USDA’s been looking at salmonella from pond-raised catfish Next slide So, I mentioned we used the metagenomic approach, expert solicitation but — and — to come up with a panel of organisms to target with culture-dependent methods And this is what we saw So, I mentioned salmonella We’d be interested in knowing a resistance in salmonella from seafood But we only got two isolates out of the first — I think this is about the first 300 samples we looked at We got very few E. coli, no high prevalence of staph aureus Aeromonas, as we saw from the metagenomics, was predominant compared to the other species Vibrio, mainly from shrimp And then, at the end — and enterococcus, also, fairly common And at the end there, you see the carbapenem-resistant enterobacteriaceae And I would just say that’s mostly intrinsic resistance among some of the odd genera that

we’re getting And some of those are included in the sidebar here Some of the other genera that we recovered in this first pilot phase So, next slide, please So, here’s the — here’s a profile of the resistance Again, we’ve recovered almost 7,000 isolates from this first 12-month study This is data on about 300 Since the slide was submitted, I think we’ve got data on about 1,000 But it’s not much different than this And this shows just the enterococcus and vibrio And there’s some resistance there; tetracycline, mainly in the enterococcus We had a vancomycin-resistant isolate You can see some of the other data there, some erythromycin-resistance Among the vibrio, really just some streptomycin resistance in, say, half of the isolates, on average I think the amp resistance in the sequencing we’ve done, so far, many of those are chromosomal genes And some vibrio species are considered intrinsically resistant to ampicillin So, we’re sorting through whether this shouldn’t be adjusted, in terms of using this as a sentinel for the carriage of resistance genes that pose a public health threat Next slide, please So, this is back to the CRE So, we had a high prevalence, like I said, and most of those were intrinsic resistances And the two that did have a transmissible carbapenemase-resistance gene, there were only two One was Acinetobacter baumannii We heard from Michael Craig about the importance of that in the Threats Report and, then, an Aeromonas isolate And they had the blaNDM-1 gene, along with an array of other linked resistances Next slide, please So, overall, I’d say it’s fair to characterize the resistance profiles as fairly tame, at this point And maybe that reflects, you know, the fact that, overall, there’s a relatively slim portion of the total drug use going into aquaculture, at the moment, although we do know there are certainly low side of intensive uses from what we’ve heard today from some of the presentations We’re carrying on, as I mentioned, to see what genes are underlying those resistances through metagenomic sequencing And this shows that, you know, we can track those resistance genes from metagenome that correspond to the phenotypes we’ve seen, but with the added advantage that we don’t have the limitations of culture here And I really think that’s important to keep repeating is we are worried about the fact that we’re not culturing for anaerobes Hopefully, if there are anaerobes present in these commodities, we’d capture the resistome from those or unknown genera that haven’t been successfully cultivated So, we’re hoping to capture a comprehensive resistome using this method alongside culture Next slide And this just shows that, you know, we can divvy it up even further by specific allele type and for each resistance by the source of the retail meat So, we’re early in the process As Sebastian said, we’re sort of learning this a little bit as we go along We want to make sure that we’re making the right balance between resources across the program, how much to invest in cultivating a fairly narrow vision of resistance in organisms that we lab processes for versus investing in the metagenomics approach in looking at it as a resistor monitoring project, if you will, where the resistance gene itself is maybe what we should consider as the hazard or the point of focus, rather than a number of sentinel organisms, which have different capacities to carry resistance and which we happen to be cultivating So, we’re going to take this two-pronged approach forward into this year, where I mentioned we’re doing the five genera And we’re going to continue to do the metagenomics and, then, hopefully, have a more complete picture for you next time Thank you very much >> Aileen Marty: Thank you very much, Dr McDermott That was a very interesting conversation; a little bit reassuring, especially after Dr. White’s presentation [laughter] And thank you, also, Mr. Belle, for your very interesting insights into regulatory issues, and certification process, and so forth That was wonderful And at this time, I’m going to go ahead and open it up for questions And if I may, I’ll go ahead and ask the first question of Mr. Belle And my quick question to you is would it help, or hinder, or have no effect to your industry if the federal government required the certificates that your consumer groups, such as Whole Foods, you mentioned, is currently asking of you? >> Sebastian Belle: I want to make sure that I understand that question clearly Are you asking if the standards that are in those certificates were placed in law, would that be helpful? I think the short answer is no And there are a couple of reasons for that Number one, on any given day, one of my farms probably has an auditor from multiple different

certification schemes on it They are complying with certification schemes from at least three, and maybe four, major different certification programs for individual customers So, the customer comes to one of my farmers and says, “I want you to certify by this standard, this scheme.” And another customer comes to the same farm and says, “I want you to certify by this standard and this scheme.” So, in one way, yes, if there was one system that was required by law, that would simplify things The challenge is that the market is moving very fast on this and different customers are requiring different standards And so, it is tough for a farmer to turn to a customer and say, “We will only certify to this standard,” because they are the customer, right? So, we comply with the law And the law in the United States is actually quite strict As an example, we do not administer an antibiotic unless there is a positive disease pathogen hit That pathogen has to be tested for sensitivity before an antibiotic is prescribed And the veterinarian has to prescribe that antibiotic And so, there is a system in place, at least in the U.S., which is quite strict In addition to that, if we use antibiotics, our national pollution discharge permits, NPDES permits under the Clean Water Act, require us to test the environment And this goes to a question that was asked earlier about what do we know about what’s going on in antibiotics in the environment if they’re administered We are required by law, by our permits, to test around our farms if we administer antibiotics And there’s 20 years of data out there, in the local state environmental departments, if you will, that are compliant with NPDS on what happens to those antibiotics In the case of Maine, we have only had two detections in the wild, post-administration of antibiotics In other areas, you know, there are different results So, I’m not going to say that everybody’s squeaky clean But the challenge, I think, also, with embedding some of this stuff in law is the technology, from a surveillance point of view and from an administrative point of view, is moving so fast that if your standards are overly prescriptive, you actually inhibit innovation And that, from a farmer’s perspective, is a real problem And it’s not just to do with antibiotics It’s to do with environmental impact and a bunch of other things out there So, there is a kind of a balance to be struck there Yeah I hope that answers your question >> Aileen Marty: That was excellent Thank you very much Christine Ginocchio has a question >> Christine Ginocchio: I’d like to thank both of the speakers It was very interesting I have two questions; one quick one for Dr McDermott And this happens to do with — okay, let’s see Which one was for you here? I lost my train of thought for a second Yes, your NDM-1’s You had two NDM-1’s So, they’re relatively rare in the United States compared to something like KPC So, do you — were you able to trace where the fish came from that brought in those NDMs? Was it from China or India, where we have very large numbers of NDM-1’s? >> Patrick McDermott: Yeah So, we harvest all the metadata we can from the packages from the store, right, so we have any label indications on there: if they have any claims of rate of production claims of — used with the — raised with antibiotics, whether they were frozen, what type of salmon, whether they — who distributed it, and so on So, I don’t know what those two are, specifically But we have and capture all the information that the package makes available And, you know, you’re right It is an important resistance, and which is why we’re going to continue to do that selection, going forward I think that’s the type of — you know, it might be a low return, in terms of the number of isolates, but given the criticality of that resistance and its apparent love for other resistances, as you could see in that profile, we think it’s important to carry on with that sort of testing So, whatever’s available on the package is the extent of information that we can use to glean where it came from, you know? >> Christine Ginocchio: And my second question is for Mr. Belle You talked about the difficulties in making an actual diagnosis of the type of infection In your industry, how are diagnostics regulated? Is it like we have IBDs for humans that go through the FDA? Are these molecular-based tests or — and then, you talked about susceptibility testing

We have enough problems with setting human breakpoints for interpretation of susceptibility data How do you do that in fish? >> Sebastian Belle: Great questions I’m probably the wrong person to answer them You need a veterinarian up here But I will take a stab The USDA has a national lab, veterinary lab system And the diagnostic tools that are used have to go through that national lab system So, there is a set of standards that labs have to comply with They’re ordered by the USDA And that is a moving target We are learning a lot as we go along And a colleague of mine, Bill Keleher from Kennebec River Biosciences in Maine, is probably one of the leaders in the world, in terms of the relationship between the labs and the verification of those techniques And I would encourage this committee to reach out to Bill and ask him those questions He’s been struggling with that, and working with that, for over 20 years In terms of sensitivity testing, it is — depending on the pathogen, it can be relatively sophisticated or relatively primitive Certainly, the disk test method is out there and used And that’s used by local veterinarians and by regulatory authorities The challenge we have in the United States of America is we do not have a national aquatic animal health plan So, it is by — it is state by state And the standards are established, in some cases, by the state, not at a national level Certainly, if this committee wanted to recommend one thing at a national level, it would be for the implementation of a national aquatic animal health plan That would standardize those methods across state lines; and between different species; and would be tremendously helpful, frankly, to the regulatory community, as well as to us, as farmers Because we often move animals inter-state And sometimes regulations in one state are not consistent with regulations in another state, both from the diseases you have to test for, the methods you use So, there is a need, at a national level, for that kind of national program >> Aileen Marty: Thank you Paul? >> Paul Plummer: Yes So, just a quick follow-on question related to those diagnostics So, I think we’ve talked about it and certainly heard over the last couple days on the human side the challenges with diagnostics and access to bedside diagnostics, those types of things Certainly, in veterinarian medicine for terrestrial animals that’s a challenge for us My suspicion is that’s even a larger hurdle for you, as a fish farmer, as fish farmers So, I was wondering if you had any comments on that related to what impact lack of rapidly-accessible diagnostics — you mentioned that you have to have those cultures and sensitivities What’s the turnaround time on those types of things and how does that impact your ability to treat those animals? >> Sebastian Belle: Sure So, again, probably the wrong person to answer this But I will tell you, we — I mean, there are three common methods: there’s histology; there’s culture; and then, there’s RT-PCR And one of the challenges we have found, particularly with aquatic animal diseases, is sometimes those methods and those diagnostics don’t agree with each other So, from a regulatory point of view, we have, as farmers, pushed for a minimum of two of those tests confirming in the same category, if you will So, if there’s an RT-PCR detection, we look for some confirmatory test to confirm that The reason we do that is because, particularly in some of the viral cases — ISA would be a good example of that — we know now, in retrospect, that we probably killed several million fish as a result of RT-PCR positive hits that were actually false positives And that cost us millions of dollars And so, we have learned, over the years, that we need a couple of confirmatory tests together Typically, you know, RT-PCR comes back relatively quickly Obviously, histology can come back pretty quickly It’s the cell culture that’s the longest, and, particularly for viral pathogens So, it varies from pathogen to pathogen So, if we can have a 10-day to two-week turnaround time, we’re pretty happy on two out of three tests >> Paul Plummer: So, then, I had a second question, if I can So, this one for Dave And I don’t know You may not know this, David [laughs], so — but we’ve also quite a — or had some discussion on duration of use And well, you know, and so, I was shocked, kind of, by your sulfa withdrawal period

There was 42 for salmons and then three days for catfish So, I was not clear on if that’s a different in physiology, if that’s a difference in how they’re farmed, or if you’re not sure about that, or a difference in when those labels were approved and methodology there >> David White: Yeah, I’m not sure I’m the right person to answer that, that one, Paul That’s more going back to the claim, I think, and the data that was submitted to FDA when that therapeutic was approved in aquaculture But if I could, also, to respond to Christina’s question, there is a VAST committee in CLSI and there is an approved document for guideline for aquatic pathogens So, there is stuff out there, if I remember, Mike >> Michael Craig: I was just looking, as we were talking here before come on I think there’s — but are there breakpoints through this? >> David White: Yeah, I think there are — >> Michael Craig: There are? >> David White: — breakpoints for — >> Michael Craig: There are — >> Male Speaker: [inaudible] >> Michael Craig: Okay, yeah So, I might — also to return Paul’s question to Dr. Flynn >> William Flynn: Yeah, Paul I’d have to follow-up to look at those specific products to see the history on the development of those withdrawal periods >> Paul Plummer: Yeah, no problem Thanks I was just interested in trying to think about if it was difference in currents, or how it’s farmed, or something like that >> Sebastian Belle: Well, I — if I could just jump in I think, you know, one of the challenges is the difference between warm-water and cold-water species, right? And withdrawal times are influenced by that So, that’s part of, certainly, what’s going on there >> Aileen Marty: Okay If there’s no further questions or comments, we’re going to head and close this session I pass this back to Marty >> Martin Blaser: Thank you very much We have finished the regular program And, now, we’re ready for our second period of public comment I ask the — our panelists to excuse themselves And we’ll ask Dr. Kevin Kavanagh to come up to the microphone as our first speaker Dr. — >> Kevin Kavanagh: Well, thank — >> Martin Blaser: — Kavanagh, the floor is yours >> Kevin Kavanagh: Thank you The government of China has received worldwide criticism over the almost one-month delay in their public notification regarding the coronavirus But we must ask: is the United States any better on notifying the public regarding dangerous outbreaks of resistant bacteria in their healthcare facilities? In 2013, I only found out about a highly-dangerous outbreak of MRSA in a nearby Appalachian hospital from a USA Today reporter, who, by chance, Googled and found a governmental slide set which was mistakenly posted in a public folder In 2016 and 2018, I found out about CRE outbreaks in Kentucky from the CDC’s MMWRs The outbreaks had occurred months to a year later prior to publication The hospital was never identified But compared to the CDC’s rapid and urgent public reporting of a resistant pseudomonal outbreak in a Mexican hospital, one begins to understand how politics, and not science, is shaping our infectious disease policy Of the four CDC’s 2019 urgent threats, which are emerging hospital-acquired infections, only one, C. difficile, is publicly reported on a national basis Those reports are delayed more than nine months, which limits their public usefulness All too often, the excuse is given that transparency will cause the public to panic, or that these organisms only effect the frail and the elderly, and we should not have heightened concern There is little evidence of the former, with notification of pathogen outbreaks in the food sector And being over 65, I fall into a high-risk category And, for me, life is no less precious Before we criticize other countries, we need to get our own house in order We need more comprehensive data for action, complete public transparency, and citizen notification of dangerous outbreaks Thank you >> Martin Blaser: Thank you very much, Mr Kavanagh I’ll now call on Tamara Johnson, Magnolia Medical Technologies Ms. Johnson >> Tamara Johnson: I wanted to thank you, sincerely, for the opportunity to have been here the last two days It’s been exceptional and extremely educational So, thank you Yesterday, I had the opportunity to speak about the perilous patient pathway caused by blood culture contamination and the impact that that has upon antibiotic resistance The current benchmark for contaminated blood cultures is at 3 percent While this sounds like a low number, it allows for an almost 50 percent positive blood culture error rate This impacts over 1.2 million patients every year in the United States

As a nurse leader deeply concerned about the number of patient deaths we see each year from MDROs, the request for this council is to set that new blood culture contamination rate at less than, or equal to, 1 percent This requested new benchmark of 1 percent or less has been proven sustainable in many hospitals and multiple controlled clinical studies that are peer reviewed and published in renowned medical journals These sustained hospital outcomes as low as 0 percent over 11,200 cultures and 0.2 percent over 1,800 cultures are achieved using evidence-based practices and an evidence-based disruptive technology called ISDD, or initial specimen diversion device It is also proven to reduce vancomycin days of therapy, hospital-wide, by 36 percent And that was presented at Shay This requested new benchmark is in line with the recently published clinical microbiology reviews article It was a consensus article by thought leaders in this area Prior to ISDD, we did not have a sustainable solution But now we know that zero and near zero are possible and sustainable Our patients and the viability of our antibiotic therapy depends upon us delivering quality healthcare with diagnostic stewardship that first prevents harm Thank you >> Martin Blaser: Thank you very much I’d like to call on Dr. Hua Wang from the Ohio State University Dr. Wang >> Hua Wang: Thank you, Dr. Blaser As mentioned in my past comments, it is essential to spell out the direct cause to many of the problems we have heard so far, whether [unintelligible], or massive antibiotic resistance, and even the rapid surge of opportunistic pathogens in — is actually due to the mainstream oral antibiotic administration in human medicine, and food animal production, and using gut-impacting drugs That’s why the problems started in industrialized country since the 1960s because we switched from injection to oral derivatives, first, but a lot later in developing countries The original study on the assessment of the impact of oral versus injection of ampicillin and tetracycline by my team was published and use released by American Society for Microbiology in 2013 and, later, supported by further studies on vancomycin, and, now, [unintelligible] by other teams in the United States It is further important to recognize that antibiotic applications in medical procedures are essential and inevitable While microbiota transplant may help recover some losses by antibiotic treatment, it has never been able to recover all And the practice further introduces a new risks to the host, such as the death case reported by FDA last year due to acquiring ESBL E. coli from the donor While it is good to see [unintelligible] allergy test and de-labelling of patients on their gender, which is related to injection application, we also recognize that penicillin still can cause severe allergic reactions, including death Furthermore, the prevalence of ESBO bacteria, such we repeatedly heard, potentially negates the function of penicillin So, penicillin is no longer the same magic bullet as for long time since the World War II The good news is, besides, penicillin, there is a long list of antibiotics practically have been used in hospitals by injection worldwide, many with very mild or no obvious allergic reactions Despite some antibiotics still partially excreted through the liver by a route impacting gut microbiota, research data have also demonstrated that injection still reduces the disruption of healthy gut microbiota caused by oral drugs Spelling out the exact problem due to oral administration is further important for new antibiotics being developed, introduced, to minimize similar resistant problem oral penicillin derivatives has caused — have caused Therefore, the new antibiotics can be the next measurable, lasting for a long time What really needs to be done is reintroduce muscle injection as an option for as many antibiotics as possible and assessing the impact of each drug on gut microbiota, oral versus injection, providing doctors with solid evidence for therapeutic decisions Furthermore, current doses — dosages used in medical injection are quite high because the goal is to treat severe infections For prophylactic purpose and the treating mild infections, the dosage by injection can

be further reduced, so is the side-effects Up to 350 million antibiotic prescriptions were given annually in the U.S. alone, most being oral The U.S. population’s only 330 million in 2019 >> Martin Blaser: Dr. Wang, your [inaudible] >> Hua Wang: I trust that the panel can recognize the stressing need to mitigate this direct, unnecessary, selective, and disruptive pressure by oral antibiotics as soon as possible >> Martin Blaser: Dr. Wang, your time is up >> Hua Wang: Thank you >> Martin Blaser: Thank you I now call on Tanya Gottlieb from MeMed >> Tanya Gottlieb: Good afternoon Thank you for the opportunity to comment on this — >> Martin Blaser: You should speak closer — >> Tanya Gottlieb: I can’t >> Martin Blaser: — because we can’t hear you >> Tanya Gottlieb: I’ll just hold it Thank you for the opportunity to comment on this listening session on antimicrobial resistance Yesterday, Dr. Rothman described the alternative approach that we, at MeMed, and others in the field are taking to address AMR Instead of trying to detect the pathogen, we weed out the individuals’ immune response to infection And based on a computational algorithm output, a likelihood score of bacterial versus viral infection is our diagnostic test result My comment is to highlight the potential of the host-based approach to compliment direct pathogen tests and help reduce diagnostic uncertainty for [unintelligible] at the frontline There has been a lot of discussion over the last two days about ensuring the appropriate antibiotic is used for bacterial infections by determining the bacterial strain and mapping susceptibility My ask to the council is not to forget the many instances today where diagnostic uncertainty leads to administration of antibiotics to patients with viral infections Just as an example, in an observational clinical study we just completed in Germany and Italy of children presenting to the emergency department with respiratory infections and fever with outsource, we enrolled 628 children who were assigned a true diagnosis by expert adjudication as viral Of these 628 children with viral infections, 186 children were recorded as prescribed antibiotics, which is roughly 30 percent Similarly, a study by Fleming-Dutra and colleagues suggests that antibiotics are prescribed to more than 30 percent of individuals presenting with antibiotic-inappropriate respiratory diagnosis in urgent care centers in the U.S Dr. Blaser referred to the statistic in the question and answer earlier I hope that the council will consider that the use of rapid, inaccurate, host-based tests that differentiate between bacterial and viral infections has potential to reduce this unwarranted use of antibiotics driven by diagnostic uncertainty, and, in this way, help to reduce the unintentional harm that Dr. King mentioned, and reduce antibiotic microbial resistance Thank you >> Martin Blaser: Thank you I’d now like to call on Lisa Weddig from — [coughs] excuse me — National Fisheries Institute Ms. Weddig >> Lisa Weddig: Thank you My name is Lisa Weddig I’m the vice president of Regulatory and Technical Affairs with the National Fisheries Institute NFI has been the nation’s leading advocacy organization for the seafood industry for 75 years Our members range from harvesters, growers, processors, importers, distributors to retail and food service Maintaining consumer confidence in seafood products, or the safety, quality, and integrity of seafood products is a top priority of our membership So, today, I’d like to thank the PACCARB for addressing aquaculture We hope that this will be the start of future considerations by the advisory committee While certainly not as large as other livestock industries in the U.S., it is important to address antibiotic use in raising of fish, crustaceans, and other sea animals, especially since the demand for farm-raised seafood will continue to grow So, there are some challenges that face the industry And I think you’ve heard most of these through the excellent presentations earlier The vast majority of farm fish consumed in the U.S. is raised in other countries In addition, the U.S. is not the sole market for the finished product Many producers and processors overseas are challenged with understanding the regulations and varying lists of approved aquaculture drugs by the importing countries And these will often differ from what is allowed in the growing country That being said, minimizing the use of antibiotics and other drugs in aquaculture is an issue that must be addressed with a collaborative global effort And aquaculture species are diverse; we’ve heard that Fin-fish, both fatty and lean, which is probably part of the withdrawal differences — salmon’s

a very fatty fish So, fin-fish, crustaceans, mollusks, frogs, sea cucumbers: all these are farm-raised And they share only a single trait: that they’re raised in water Treatments and husbandry practices are not a one-size-fits-all In addition, the list of drugs approved for use for aquaculture in the U.S. is small: about 10 And we heard that only three of those are, actually, antibiotics And not all of these drugs are approved for all species FDA has only one drug approved for use in the raising of shrimp And that’s — shrimp is the most commonly consumed seafood species in the U.S And since 100 percent of the farmed — almost 100 percent of the farmed shrimp does not occur in the U.S., there is little incentive for drug companies to seek FDA approval for new drugs And we heard that many of these industries are not vertically integrated A single processor, overseas, might source product from hundreds or even thousands of ponds So, capacity-building is needed to ensure that there is a basic understanding of the basic practices that promote healthy growth To that, then, the Seafood HACCP Alliance, a 25-year partnership between U.S. government, academia, and the industry, is developing training materials to provide processors of farm fish with tools they need to link farm practices to a robust [unintelligible] of controls And then, finally, contrary to popular beliefs, the U.S. seafood-importing community does not actively seek out products that contain residues of unapproved drugs Importers support any efforts to minimize the use of antibiotics with raising fish, such as through capacity-building efforts, third-party certifications, and industry verification of farm practices >> Martin Blaser: I’m sorry, your — >> Lisa Weddig: Thank you >> Martin Blaser: — time is up Thank you I now call on Shannon Rush, a patient advocate representing herself >> Sharon Ross: Hi My name is Shannon Ross I’m actually a pediatric infectious disease physician from Birmingham, Alabama I’m at UAB in Children’s of Alabama So, I’m here to talk about antimicrobial resistance, just to make everyone aware about what a problem it is in my hospital and, as we know it is, you know, within the U.S. and globally So, I run our hospital antimicrobial stewardship program And we are the main tertiary care hospital for our state And we’ve actually just done our 2019 [unintelligible] And, unfortunately, our data reflects the CDC and community acquired resistance is on the increase So, we are seeing ESBL rates, unfortunately, of up to 10 percent, community-acquired UTIs So, the unique thing about pediatrics is that, to begin with, we don’t have all the available antibiotics So, fluoroquinolones, tetracyclines: we do not like to use in children They have toxicities And unless there’s a really good reason, you know, we really prefer not to use these because of potential toxicities So, to start with, we’re left with a smaller sort of pool of antibiotics But, as you know, it takes longer for the newer classes of antibiotics to get into children, even though we know the antibiotic market is so broken Just this summer, I had a medically-complex child I had to take care of He had a multi-drug resistant urinary tract infection We really had no available options and I had to use one of the new combination antibiotics with very little information on how to dose it There was only one Phase One small study So, I had to have this conversation with his mom because, again, we don’t have these studies in children about how we really aren’t sure of the dose, we aren’t sure of the toxicity But it was really our only alternative So, you know, don’t forget the children, right? Because they’re definitely as medically-complex as adults But, yet, you know, we’re — we have less to start with So, we need to get these antibiotics, sort of, through the pipeline We need to get them to children You know, we are a robust antimicrobial stewardship program And thanks to, you know, efforts, we have reduced our hospital-acquired infections But, certainly, our community-acquired multi-drug resistant infections are very real Thank you for your time >> Martin Blaser: Thank you Final speaker I’ll call on Laura Sage, a patient advocate representing herself >> Laura Sage: [inaudible] >> Martin Blaser: Ms. Sage >> Laura Sage: Hi I’m the owner/operator of Red Bird Acres Farm and — >> Martin Blaser: Can you — >> Laura Sage: — we’re — oh — we’re located in Corvallis, Oregon And we’re a certified animal welfare approved farm, raising pigs and poultry on pasture And we’ve worked diligently to develop humane animal handling techniques that greatly reduce

the need to use antibiotics on our farm So, we work closely with our veterinarians to accomplish this, as well as rely on the work being done by Oregon State Veterinary Diagnostic Lab and the extension agents in our region As a farmer, I’m directly affected by the Veterinary Feed Directive, as well as the plan to move all over-the-counter antimicrobials to under veterinary supervision And as a farmer, we’re in full support of that move, as we see it as benefitting both the health of the animals on our farm, as well as the community that we’re striving to provide health food for Thanks >> Martin Blaser: Thank you very much And that concludes our public comments And now it’s time to begin to conclude this listening session meeting of the last two days First, I’ll call on Dr. King to see if he has any final comments to make >> Lonnie King: Thanks very much, Marty And thank you for the audience and all of our speakers It’s been a great two days We really appreciate that And also, thanks to the people online, who have been listening to this, as well You know, the one thing that comes to mind, to me, is an old quote that says, “When you pull on a string in nature, we find out it’s all connected.” So, really, the last two days, we found out that it’s all connected, from aquaculture and finned animals, to four-legged, to two-legged, to monogastric and ruminates So, we are accountable, and we all are responsible And it’s going to take a real holistic approach to really get ahead of this problem So, we’ve heard a lot of that over the last couple days I’ve been encouraged by what we’ve heard, and with some of the new innovations and new products coming out, and how CARB-X, and other incentives, are really helping to kind of drive that new market So, we appreciate that And I guess the last thing that I kind of took away from today is the — also a reminder of outcomes’ research, as we talked about some of the products especially used in food animal and in companion animal, that a lot of products being used that are really kind of untested And we need to go back and understand outcome research, which we talked about a few sessions ago >> Martin Blaser: Thank you very much And I’d also like to offer my thanks to our panel, to the speakers over the last two days, from our audience for their attention and fortitude And I’m also impressed by the issues that Dr. King raises and about how global the problems that we have are And, yet, how important it is for us to get our own house in order And there was a discussion today about do no harm as a background for both medical and veterinary care I’d like to mention that And we also talked yesterday about the continuity in infectious diseases, including bacteria and viruses, which is particularly relevant So, I wish everybody a safe journey home And we hope to see you soon This meeting is adjourned And the committee will assemble for an administrative session in 10 minutes on the seventh floor Thank you very much >> Female Speaker: Produced by the U.S. Department of Health and Human Services at taxpayer expense