Animal & Veterinary
Resistant Foodborne Infections and Policy - Consumer Advocate Prospective by Steve Roach, Food Animal Concerns Trust
MR. ROACH: Hello. I am Steve Roach from Food Animal Concerns Trust and again I would like to thank the organizers for inviting me to present on the consumer perspective on antimicrobial resistance and enteric pathogens. My organization is -- I also would like to thank all of you that have stayed here throughout the whole day and you are still here to listen to me talking as the final speaker in this meeting.
Food Animal Concerns Trust is a consumer advocacy organization that promotes policies on-farm that can be used to improve the safety of meat, milk, and eggs. So we look at what type of on-farm practices can be promoted to prevent human foodborne illness.
One of the areas that we think is very important and that there is room for improvement is in the area of antimicrobial use on farm. So that is why we work with this area and the related antimicrobial resistance risk.
I would say that we are not only concerned about resistant infections. We did a lot of work on looking at the problem of Salmonella enteritidis related to shell eggs and we were involved in a process of trying to get regulations passed on that as well for many years.
This year for the first time we are actually going to have some on-farm controls for Salmonella enteritidis mandated in the egg-layer section.
But because antimicrobial resistance is a very big issue and it is a difficult issue, we actually work in coalition with other organizations. So we are a member of Keep Antibiotics Working Coalition which is a collection of consumer, farm, environmental, public health organizations that are all trying to grapple with the problem of antimicrobial resistance linked to the use of antibiotics on farm.
Because it is an international problem as well, so we don’t only work on it -- we also -- I work in coalition with Consumers International which is again a coalition of member organizations, over 350 organizations around the world.
So the question -- I kind of don’t actually want to do these next slides. I don’t think I should have to, but I will because there have been some questions brought up whether there is actually enough evidence for taking action.
What I want to do is present a little bit of the “what would evidence look like” that you would use to base taking action on antimicrobial resistance. So what is the public health risk?
There are basically three factors. Does antibiotic use on farms select for resistance? Then are people exposed to bacteria in significant quantities or are there enough resistance determinants that it causes humans to actually get the infections? The final thing is there any significance? Does it matter? Maybe we are getting lots of resistant Salmonella, but it is not really important. It doesn’t have any human health impact. So those are the three areas.
And of course, there is a vast -- there are mountains of literature on this, but I am just going to pick a little bit and say there is some evidence and if you want to look for more you can look at it and you can say it is not sufficient to take action. But there clearly is evidence. I just want to talk about the examples of the type of evidence you would look at.
So the first one is looking at does on farm antibiotic use lead to increased resistance in bacteria on farm? And I just took three studies from different food animal sectors. The first one in feedlot cattle, looking at chlortetracycline plus sulfamethazine and feed was linked to increased tetracycline and ampicillin resistance in E. coli.
I mean the tetracycline one is expected, but I also think it is interesting that it is interesting that you find ampicillin resistance too. Probably this is because you have co-resistance where they are linked.
But one thing that I would say that suggests if you just do simple single bug/single drug risk assessment, you are going to miss this effect. So if you look on the farm how much tetracycline resistance you have, then you look in food, and then you look at the human health effect of the tetracycline resistance, you may miss part of the risk and I think that is an important perspective.
The second study was on Campylobacter and swine farms. They compared conventional farms with organic farms or antibiotic-free farms. Again, they found more macrolide resistance and tetracycline resistance in Campylobacter on the conventional farms. It is not surprising. Those are the two antimicrobials that are used the greatest amount in feed on conventional farms in the U.S.
But the interesting thing about this study by Rollo that was published this year, is that you could see reductions in resistance so they stratified their antibiotic-free farms by how long they had been antibiotic free farms. So you saw resistance was still going down after six years. So it is not something that necessarily -- so you withdraw them. It may take many years before you actually see effects. They had farms out to six years. We don’t know if they kept going down.
The final one, is just a look at broilers. Again, comparison of farms were treated with macrolide tylosin versus farms where they were used subtherapeutically versus farms where they weren’t used at all.
Again, you can find, you know, the most resistance in the subtherapeutic treatment, a medium level in the treatment levels, and where you didn’t use them at all, I think there was no resistance if you started out with a susceptible Campylobacter.
Then are people exposed to resistant bacteria? This is just a summary of some of the NARMS data. I am not going to go over this very much, but basically there is a lot of resistant bacteria in food.
A big part of it is, if you look at Enterococcus, if you look at chicken, almost all of it has resistant bacteria on it.
On my last column I said what is your chance of not getting a piece of resistant meat? You basically can sum up the probabilities as you go down, but because almost all the meat has resistant Entercocci, if you go to the store you are going to get resistant bacteria on any piece.
If you take the Enterococci out, still any piece of chicken that you pick off the shelf, three-quarters of it will have resistant bacteria to at least one of the drugs that we think are important enough to do surveillance on.
This goes on and people do get sick from resistant bacteria, so I don’t want to go too much on this because we don’t have a whole lot of time. But there are a lot of resistant bacteria and people get sick from them.
I think the one at the bottom is, you know, we focus on Salmonella and Campylobacter. I think some of the other things like E. coli and some other newer things may be of greater public health significance. But I think we are just learning about those.
The final thing is, well, you know, maybe as I said, I think that a lot of the debate is whether there is any significance or the public health significance. So we obviously are selecting for resistance on farm. I don’t think that is disputable. There is also resistant bacteria moved from farm to humans.
So the big question is what is the impact on public health? I think there are two things. You can have increased number of infections and that happens when you take an antibiotic for another reason. If you happen to have resistant pathogens in your gut, you are more likely to get infected.
You also are just more likely to get --even if they are not resistant, you are more likely to get infected, but there is two effects.
The second one that is not talked about very much is the loss of treatment options. So if you go back and look at papers until the mid 80’s, at least in the early 80’s, ampicillin was the treatment of choice for Salmonella in the U.S. Tetracycline was a treatment for Campylobacter.
We don’t use them anymore because the resistance is too high. We switched cephalosporin and fluoroquinolones. now what we see is resistance in Campylobacter to fluoroquinolones and resistance in Salmonella to cephalosporins. So I think there is a concern.
So we lose a drug. Does it mean it is not a negative effect? I think it is. I think people’s health has been harmed when you have to switch from ampicillin to fluoroquinolones.
Then the final one is just some studies showing that you actually can show associated harm to human health from some of the resistance.
So then the next thing is, okay, is there any room for improvement? I think there is. These are just looking at -- part of the problem is we don’t have good data on how antibiotics are used on farm. But I have kind of listed a lot of different sources and some of these -- all of these have limitations.
The FDA drug distribution data which they collected for years, but it was not in a form that they believe that was useful. Now they are supposed to collect it in a better form hopefully it will provide some use.
AHI surveys of its members, again there are limitations on that.
The Union of Concerned Scientists estimated use.
I think two of some very important sources are the USDA surveys of livestock producers and NAHMS, the National Animal Health Monitoring System, and the Agricultural Research Management Survey, ARMS. These actually go and ask farms how much of the antibiotics are they using.
The ARMS studies, I think, actually have more detailed data. I am not all that clear on those, but I have seen papers that have used them.
The final one are these private sources, at least as far as I can see where they have been reporting usually a single drug in a paper, this data is even better than anything we have, at least some people have talked on the poultry level where you can talk about 0.07 percent of the poultry flocks are using macrolides. You know, I think that type of data.
What is not clear to me is how available this data is to the general public and how much it would cost to get access to it. But they seem to be very fine data, in terms of some of the private sources.
Okay. So one of the major issues is the feed additive use. I just want to look at that because this is one of the more controversial areas.
If you look at from the NAHMS Swine 2006, this is a survey of producers and they cover a good percentage of them. 85 percent of the finishing farms use feed additives for growth, prevention, or treatment. The two major ones are chlortetracycline and tylosin. There is a whole long list of other ones that are used and you could go and see what those are.
Again, NAHMS Feedlot 1999; that is the latest one that I am aware of. Again, 83 percent of feedlots use antimicrobials in feeder water. Again, chlortetracycline and tylosin are the major ones.
Then in 2000, at least 67 percent of broiler farms used in-feed antimicrobials. Here they are different drugs. I think Tim Cummings mentioned it, bacitracin and virginiamycin. So it is interesting that the broilers are actually using Gram-positive drugs for the major ones.
One thing you can look at this, while 15 percent of the swine farms were not using any antimicrobials, 17 percent of the feedlots were not using them. I don’t want to say that 30 percent of the broiler farms were not using them because they may have just used them and the way the data was presented you can’t figure out exactly whether the farm used them at all.
So then looking at one of these uses. So we have 85 percent of the swine farms are using them. There is pretty good data out there. Consistent studies over the last ten years that a lot of this use is unnecessary.
Part of the studies at the growth promoter ban, if you looked at what happened in Denmark. Again, the people that like to say they were a big problem, the challenges were in the wieners, and I think that has been acknowledged by most people.
So there was no -- the impact on withdrawing the growth promoters in Denmark on the finishers was minimal. The same data you can find from the U.S. Steve Dritz in 2002 at Kansas State University looked at data from very large commercial farms in the U.S.
Again, he found no benefit from using the feed additives. He doesn’t break it down between whether it was used for prevention or for growth promotion. He just looked at whether they put it in the feed or not. They did not find any benefit at the finishing level.
Gay Miller from the University of Illinois found that productivity was reduced by antibiotics used for disease prevention in finishing swine.
McBride in 2008, no relationship was found between productivity and antibiotic feds during finishing. So in the final one I put on there, there are also quite a few studies that showed okay we talked about growth promotion and prevention and a lot of these studies really don’t distinguish them because it is kind of hard tell why they are using a specific drug because they are approved for both prevention and growth promotion.
But oral tetracyclines are very commonly used in swine for respiratory disease treatment, but there have been studies, at least going back since 1985 showing you don’t have blood plasma levels high enough to actually get a treatment effect. But they are still used widely in the swine industry for treatment of respiratory disease.
So what this suggests to me is there is good evidence that you have room for improvement in this.
I don’t want to say that antibiotics don’t provide any benefits. I mean, the same studies I cited will show that you get benefits if you use feed additives. Again, I think it is usually not very helpful to distinguish most of the studies between prevention or growth promotion.
But in the nursery phase, you can show productivity benefits. I think in necrotic enteritis controls in broilers there is concern of the U.S industry. I think it is a real concern.
Again, the producers in Denmark didn’t seem to have that. They were very few problems after it, but there may be some differences, but it does -- there is some evidence.
The final one is liver abscess control in feedlot cattle. Again, and this is because we have created a system where we basically move cattle to the Great Plains and we feed them corn. The reason we have to do the liver abscess control is because of the nature of the diet.
Now to create a different system of raising cattle is probably more expensive but we have created a system where, at least under our current management systems, we have problems like liver abscess control if we don’t use the feed additives in it. So that is why we are using tylosin and chlortetracycline.
There are alternatives. Most of these you can start reducing the problems by modifying diet. Animal proteins and diets are fairly highly linked to necrotic enteritis in broilers. The diet in the cattle, if you reduce the amount of starch in the diet than you can reduce the liver abscess problems.
The nursery phase, you know, I think there are challenges but again, what was done in Denmark is they modified the diet a lot. They use alternative feed additives. I think vaccines -- it would be nice if we had -- one of the big problems with the swine is Lawsonia. If we have a decent Lawsonia vaccine we could use less drugs.
My last point on there is dairy cattle and layers manage without routine antimicrobial use because they can. If you are harvesting something continuously, you can’t put the drugs in. Where we have not been able to use that, we have systems that adapted to lower use.
So we have a problem. I think it is a real problem. For the rest of the talk, I would just like to talk about some ways -- okay. How can we go about moving in the right direction?
Research, I think there is lots of room for research but these are areas that I would just like to highlight saying we want to look at more. I think the link to human health. When I was sitting out here a lot of time, we always talk about isolates and I think sometimes the isolates are isolated.
You know, we can look a lot about what are the isolates, but what is the public health significance with all the data collection that we are doing? I think we need to keep that in mind.
So I think one of the big areas we need to do is look for links to human health. I think source attribution studies are really important. I think we need to do a better job on that.
I also think, okay what is the public health significance of resistance in Salmonella and other organisms? The emerging pathogens, I think we need more work there.
The economic cost of resistance. Recent studies I have seen it is a cost of, at least for hospital-acquired resistant infections, $24 to $32 billion per year in the USA, so huge numbers. So even if the animals’ contribution is very small, one percent of $24 billion is quite huge.
Then the other side, I really think we do need. I wish we could find a good solution for these three issues that I said, necrotic enteritis control, a way to wean pigs without giving them antibiotics, and a way to raise cattle where we don’t have to give them antibiotics. Whether it is on the feed -- if we could find it -- I think we are not going to be able to shift it, so how do we find a feedlot diet where we don’t need to use antibiotics?
So this is a surveillance meeting. We are talking about NARMS and I will say these are my two things where I think we need to improve. Surveillance and I would just say, Tom’s presentation, I agree with it. I think what we need to do, we have the 2007 Science Board recommendation, we need to find a way to get the sampling better and I think there is agreement on that.
The problem is how do we get the resources and how do we make it work? I think that is something everyone needs to work together to do.
The other side, I think we need to have better antimicrobial use data, but I would also hope that the existing data that we have, that we also use it. So there are sources of data. I think the USDA actually has some pretty good programs for collecting data.
I think the poultry industry is one area where I would wish we could get better data. I think the poultry industry has done a very good job in reducing antimicrobial resistance and it would be nice if we could actually see some data on that. We have that Chapman paper from 2002, but the data goes from 1996 to 2000.
The final thing is okay, we have a problem. What do we do about it? That is what I put under this risk management. We have a long history of inaction on feed additive uses. 1977 proposals by the FDA to withdraw feed additive use of tetracycline and penicillins. As far as know, these are still open. There are notices of opportunity of hearings so the FDA is sort of still in the process of withdrawing these, but they are moving dreadfully slow.
In 2003 we had Guidance 152 which is a new way of assessing risk in antibiotics used in food animals. At that time, FDA at least indicated in public meetings that they intended to apply guidance 152 to prior approvals. We do know that they did apply it to the penicillins because we have seen letters that they sent to the sponsors of penicillins. But is have never gone beyond that and they have never made their assessment public.
In 2005 there was the withdrawal of the poultry approval for fluoroquinolones and that has been discussed here. I would just say, those of you saying that the NARMS data shows that we should probably not have done that, I don’t think it is that simple.
I think you can show, if you look around the world, we could do much worse. We could do much worse. We are at about 25 percent resistant in Campylobacter. You could go right up to 100 percent if you want to, depending on how you used it in the farms.
Also, I think if you look at where it is in Salmonella, if you look at the reduced susceptibility to quinolones, in the U.S. we are kind of in --the best way I could find comparing U.S. data -- we are kind of in the middle of the pack with some of the European countries. There are European countries that are much, much higher levels in Salmonella but we could do worse.
I think we need really -- if you look again at the study by Rollo, it may take six years before you see it going down.
Then there are some recent actions. In 2008, FDA announced that it was going to withdraw the extra label use or prohibit the extra label use of cephalosporins and then they never did it. In March 2010, they requested comments on veterinary feed drugs.
And what I would like to talk just a little bit more about and then everyone can go home, the June 2010 Draft Guidelines on the Judicious Use of Medically Important Antimicrobials in Food-Producing Animals.
These are the two principles that are in it, but basically it says the FDA thinks that growth promoters are not a good way to use antibiotics in food-producing animals and that we need to have vets have more say in how they are used.
That is good policy guidelines but there is no timeline or plan to implement the policy. So they are good words but without any type of proposal for how you get those words translated into the actual activity on farms, changes on farms, I find it not very helpful at this point.
As far as I can understand, there are two mechanisms that they could get actually these policies implemented on farm. The FDA could show that a particular use was unsafe and take action to withdraw which would open up to legal challenge. Or the drug sponsors could voluntarily withdraw an approved use or modify marketing status.
I think the problem -- I don’t trust number one because I haven’t seen that FDA has indicated any that it is willing to actually do this. They have had the ability to do this all along. In the second one, I just don’t think that because FDA asked nicely that the drug manufacturers are voluntarily going to take steps to reduce their sales.
So I think the second one really leads you in risk of spending a lot of time negotiating with the industry and then you are going to basically get cosmetic changes where you may switch from, okay we won’t call it growth promoter anymore but we will have the same drugs used in the same way for disease prevention and there won’t be any actual change in practice.
Because if you want to effect public health by reducing use, then you have to reduce use. You can’t just change what it is called.
So because of that we have supported legislation in the U.S. and this legislation again addresses how does the FDA get over the legal hurdles to withdraw a drug. It returns the burden of proof to the sponsor. It covers for medically important drugs used non-therapeutically, the sponsor must show safety with the same standards as any new drug approval.
So by using the same standard all the new drugs have to, it basically says that the drugs that were approved long ago will have to meet the standard of the drugs that are coming on line now.
What we say by non-therapeutic, it includes routine prevention and control as well as growth promotion and feed efficiency.
When this legislation is passed, there is going to be some discussion of what routine means. I think that is a challenge. There are obviously preventive uses or disease control uses that are appropriate, but it is trying to figure out which ones are and which ones have room for improvement.
In addition, it sets a timeline so this doesn’t go on forever so we aren’t always trying to negotiate a solution or analyze the data. After a certain period of time it needs to come.
So thank you for listening to me and I appreciate the opportunity to speak.