Wednesday, March 30, 2011

Food animals and antibiotic resistance in humans

The U.S. food system, in which American ag producers make up the foundation, has been under attack on various fronts for the past several years. Attacks have come from intellectual leftists, global warming alarmists, trial lawyers, animal rights activists, school administrators and boards, and the major media, among others.


The food system in general, and farmers and ranchers in particular, have been accused of contributing to man-made global warming, of producing and marketing foods tainted with pesticides, herbicides and hormones, and of inhumane and cruel treatment of livestock. In a neat contradictory claim, ag producers have been accused of causing obesity and diabetes by producing too much cheap, nutritious food, while at the same time of causing food anxiety and hunger by charging high prices for under-produced crops.

Few of the claims made against the food system are objectively true. Often a single incident or hypothesis has been the basis for wildly improbable claims. Most of the attacks are logically inconsistent, yet reported with righteous fervor. Recently, in a prime-time exclusive reported by Katie Couric of CBS News, livestock producers were accused of driving up antibiotic resistance in humans through over use of antibiotics in their animals. Couric essentially argued that producers in the U.S. heavily medicate their livestock from birth to slaughter for the sole purpose of increasing growth. More pounds equals more profit, she argued, at the expense of causing a potentially devastating epidemic of untreatable bacterial disease across the country.

Couric’s report was chock-full of inaccuracies, false claims and wildly off-base assumptions and conclusions. On February 10, 2010, the former USDA Deputy Undersecretary for Food and Safety responded to the report. Dr. H. Scott Hurd, now an Associate Professor of Veterinary Diagnostic and Production Animal Medicine at Iowa State University, said that Couric got the story far wrong, and that the story as reported was wrong on nearly every point.

Here are the claims made by Couric, followed (in italics) by Dr. Hurd’s rebuttals. Hurd notes that the facts he provides represent the best available and most current knowledge regarding antibiotic use in livestock and its impact on animals, humans and food safety.

COURIC: A University of Iowa study last year found a new strain of Methicillin-Resistant StaphAureus (MRSA) — in hogs (70 percent), and workers (64 percent) — on several farms in Iowa and western Illinois. All of them use antibiotics, routinely. On antibiotic-free farms no MRSA was found.

HURD: This very small pilot study sampled fewer than 300 pigs. In it, only six farms used antibiotic-free production methods. The claim that usch production is always free of MRSA is not true as there have been organic farms in other countries that have been found to be 100 percent positive for MRSA. On the other hand, in this Iowa study, some of the conventional farms that did use antibiotics were 100 percent free of MRSA. A University of Iowa study which went unreported by Couric found conventional farms with MRSA rates in pigs of 23 percent, not 70 percent. In personnel, the rate was 58 percent, not “nearly two-thirds.” The type of MRSA that has been associated with livestock is unique and has not been found in human disease surveillance. It is very unlikely that the people interviewed for the Couric story had livestock-associated MRSA, rather, it’s much more likely these people had the very common community-acquired strain of MRSA from being in close contact with infected people. also, the antibiotics used in modern pork production are not associated with the development of MRSA. Methicillin has never been used in animals in the United States.

COURIC: Health officials are concerned if workers who handle animals are getting sick – what about the rest of us? Drug resistant infections have sky-rocketed over the past two decades, killing an estimated 70,000 Americans last year alone.

HURD: The drug-resistant infections referred to here have little, to no, relationship to any antibiotic use in animal agriculture. The types of drug-resistant infections that are lethal are often associated with hospital-acquired infections – and the antibiotic used in those facilities. According to the FDA, resistance in food-borne illness is stable to declining over the last several years. Scientific risk assessments conducted by myself and others have shown a person is more likely to die from a bee sting than have a few extra days of diarrhea due to a resistant infection acquired from on-farm antibiotic use.

COURIC: Antibiotic resistance is an emerging health crisis that scientists say is caused not only by the overuse of antibiotics in humans, but in livestock as well. Antibiotics fed to healthy animals to promote growth and prevent disease.

HURD: Strategic use of antibiotics in animal agriculture prevents disease and produces safer food.A side benefit of this use is faster growth. Antibiotics have been used in humans for more than 60 years and in livestock for about 50 years, if there was going to be an epidemic of resistance related to antibiotic use in agriculture it would have occurred by now. The fact that it has not means that antibiotic use in animals is not a major risk to human health.

COURIC: “My fear is that one of these days we are going to have an organism that's resistant to everything that we know, and we'll be left powerless,” said Dr. Thomas Cummins. “There are a lot of concerns about antibiotics being added to animal feeds that may be contributing to MRSA as well as other antibiotic resistance. Certainly the more bacteria are exposed to antibiotics in any shape or form, the more tendency there is for resistance.”

HURD: While the types of antibiotics used in animal feeds do not contribute to the development of MRSA, the concern over the development of antibiotic resistance is why veterinarians and farmers have spent more than 20 years continually improving their antibiotic use. The results of these improvements are evident in FDA-monitoring studies that show that resistance in target pathogens is stable to declining.

COURIC: There are different types of drug-resistant bacteria. Some, like E. coli and salmonella, can be passed on to people by consuming undercooked meat and poultry. Now, scientists are worried that Americans may be acquiring drug-resistant MRSA – not from eating, but from handling tainted meat from animals that were given antibiotics.

HURD: Research demonstrates that when MRSA has been found on meat, it is present in extremely low levels. Because of this, the United States Centers for Disease Control and Prevention (CDC) and the European Food Safety Authority both conclude that the likelihood of MRSA being spread by handling or eating meat is very low. As always, when meat is handled and cooked properly, there is virtually no risk of becoming sick from a food-borne pathogen.

COURIC: Evidence of MRSA has been found in the nation's meat supply. But it's unclear how widespread it may be, because only a small fraction is tested for MRSA.

HURD: MRSA is not a food-borne illness, thus testing meat is unnecessary. The CDC and the European Food Safety Authority agree that the risk of MRSA from handling or eating meat is very low.

COURIC: ‘If the bacteria becomes resistant to antibiotics, it can actually spread in many ways,” Hearne said. “It could be in the food supply, but it also can be in waters that runoff in a farm. It could be in the air. It can happen very quickly in many different ways. It's why it's a practice that has to stop on the farms.”

HURD: There is no evidence to support that these routes contribute to the human health concerns around antimicrobial resistance. Food-borne illness rates are declining, and resistance in those pathogens is stable to declining. Environmental spread of these pathogens is largely theoretical.

COURIC: Using antibiotics to help animals absorb and process food so they grow bigger, faster is a selling point pushed by the pharmaceutical industry. Because animals are packed into confinement pens, antibiotics are also used to keep disease from spreading like wildfire.

HURD: Antibiotic use is one very important tool to maintain animal health in farms of all sizes and structures. Other tools used include hygiene, proper diet and nutrition, providing the proper environment and vaccination. Antibiotics help the animals grow healthier, improve animal well-being and help provide safe food.

COURIC: But the bottom line on antibiotic use is this: no one is really monitoring it.

HURD: The U.S. Food and Drug Administration (FDA) regulates antibiotic use in both humans and animals. The FDA inspects the feed mills that would produce medicated feed. The agency also evaluates the safety of antibiotics used in animals for human safety. And, the FDA works with the USDA to conduct tests in processing facilities to make sure those regulations for antibiotic use are followed. It’s clearly a highly regulated practice.

COURIC: Antibiotics in Denmark are used sparingly and only when animals are sick.

HURD: That is true. So sparingly in fact that farmers and veterinarians are not even allowed to use antibiotics to prevent common illnesses they know are coming. They must wait until pigs suffer and die. The Danish Pilot Program resulted in an increase in diarrhea in pigs and a 25 percent increase in deaths. Many small farmers were driven out of business due to this ban. The number of farms went from 25,000 in 1995 to less than 10,000 in 2005. What appeared to be a ban on antibiotic use in healthy pigs actually pointed out the benefits of its use in helping pigs grow healthy.

COURIC: The experiment to stop widespread use of antibiotics was launched 12 years ago, when European studies showed a link between animals that were consuming antibiotic feed everyday and people developing antibiotic-resistant infections from handling or eating that meat.

HURD: No studies ever showed such a linkage. The government records clearly show it was a precautionary action due to the possibility of risk. Denmark is a very small country which produces fewer pigs than the state of Iowa. Their experiment was not on a national scale in terms of size.

COURIC: Since the ban, the Danish pork industry has grown by 43 percent – making it one of the top exporters of pork in the world. All of Europe followed suit in 2006. But the American Pork Industry doesn't want to.

HURD: In 1997, the Danish pork production was 21.2 million head. In 2008, the industry had grown to 27 million, but about 5 million pigs were exported to other European countries to be fed for market. That means that net growth in the industry was approximately 5 percent, not the 43 percent reported by Couric. The Danish Government’s own report states that since 1998, the first year of the ban, active kilograms of antimicrobials used to treat animals increased 110 percent while animal production has only increased 5 percent.

COURIC: Without growth-promoting antibiotics, it only costs $5 more for every 100 pounds of pork brought to market in this country.

HURD: According to a recent analysis by Iowa State University, a U.S. ban would increase costs by approximately $6 per animal in the first year. The total cost of a ban to all U.S. pork producers, spread across a ten-year period, could be in excess of $1.1 billion and lead to a 2 percent hike in consumer pork prices. Even though the ban raised pork prices and put small producers out of business, cost is not really the issue. The focus should be on public health. Did the ban in Denmark improve public health? Neither the World Health Organization nor I find any evidence that it did.

COURIC: Dr. Ellen Silbergeld said, “I think the Danish and European experience indicate that there will be real and measurable public health benefits. There’ll be improvements in food safety and actually in the prevalence of drug resistant infections in people.”

HURD: The World Health Organization (WHO) has stated there was no evidence of improved public health. In fact, resistant rates in human Salmonella cases have increased, and Denmark is currently experiencing their largest outbreak of methicillin-resistant Staph Aureus (MRSA) in its history. Denmark has seen a largest increase in human MRSA cases since it banned antibiotic growth promotion in animal agriculture.

COURIC: According to one study, when different countries introduced certain antibiotics on farms, a surge occurred in people contracting antibiotic resistant intestinal infections one to two years later. One infection, Campylobacter, increased 20 percent in Denmark and 70 percent in Spain.

HURD: The example of resistant Campylobacter does not relate to the use of antibiotics for growth promotion or even of any antibiotics in feed. The type of antibiotic, fluoroquinolones, was used to treat sick animals, and in the United States required a veterinary prescription. In pigs, they were delivered by giving the animals a shot. The antibiotics that have been used in feed in the U.S. are old— most have been used for more than 40 years. In addition, risk assessments have shown that they do not pose a risk to human health. FDA surveillance shows that resistance to these antibiotics in pork products is steady to declining.

COURIC: After the ban, a Danish study confirmed that removing antibiotics from farms drastically reduced antibiotic-resistant bacteria in animals and food.

HURD: The only resistance that decreased was in Entercoccus spp., which is not a food-borne pathogen. The total tonnage of antibiotic used in Denmark decreased after the ban, however, the amount of product used to treat sick pigs increased 100 percent. The key point is that the type of drug used to treat sick pigs was different than those used to prevent disease. The World Health Organization notes, “It is probable, however, that termination of antimicrobial growth promoters had an indirect effect on resistance to tetracycline resistance among Salmonella Typhimurium because of an increase in therapeutic tetracycline use in food animals. Increased tetracycline resistance among Salmonella may result in additional human Salmonella infections… since persons who take tetracycline for other reasons are at increased risk of becoming infected with tetracycline-resistant Salmonella.” Based on this, there might be more risk now than before the ban because of an increase in treatments. Also, resistance in human food-borne pathogens, such as Salmonella and Campylobacter has not decreased at all.

COURIC: Danish scientists believe if the U.S. doesn't stop pumping its farm animals with antibiotics, drug-resistant diseases in people will only spread.

HURD: That’s simply not an accurate description of what America’s pork producers do at all. Drug resistance in food-borne disease is not the major concern with human-resistance issues. Less than 1 percent of food-borne illnesses require antibiotic therapy. The human-health crisis with resistance is focused on pathogens that are often hospital-acquired. Bans, such as what Denmark implemented, will not address those issues.

COURIC: It costs very little to convert a farm to antibiotic-free. And it doesn't cost consumers much more either. The example was given showing that antibiotic-free pork production would only cost farmers $5 more per hundredweight or 5 cents per pound, so why not just do it to improve human health?

HURD: U.S. economists have shown that if those same antibiotic bans occurred in California, it would add $5 to the cost of every pig. Because I spent three months working in Denmark, I can assure you these effects are real and still present. For this reason, I hope U.S. decision makers will balance this information with the goal of protecting finite resources while feeding a growing population. Attempts to ban antibiotic use in livestock won’t improve human health, and indeed may result in an increase of food-borne disease.

9 comments:

K said...

Gol durn. I just typed out a really long rebuttal here, and Blogger lost it!

K said...

Sigh. Trying again, but with less flair this time.

I won't address the whole tit-for-tat, since I mistrust scientific arguments made from a single perspective. Sure, the guy's a diagnostician, but does he study microbial genetics? (For the record, I once worked at the same facility he's at.)

Perhaps Couric's story came off as anti-ag, but it's not agriculture that's to blame for the antibiotic resistance crisis - it's just one piece. We take antibiotics for granted in general and have not treated them like the precious resource they are. ANY low-dose use, whether in ag, or from people who don't finish their entire prescriptions, or the trend to add antibiotics to plastic consumer goods puts a selection pressure on bacterial populations and causes the ones with resistance to survive and thrive. Worse yet, bacteria can swap genes, even across species. Any antibiotic gene has the potential to spread into lots of bacterial environments.

We are overusing antibiotics as a society, and not doing enough research to find new ones. We're regressing towards the days when a simple cut could kill for lack of an antibiotic.

Anything that can reduce the use of antibiotics in animal husbandry and keep an animal's immune system up (like low-stress handling!!) is good for us all.

Prairieadventure said...

Wish I could have seen the one with more flair!

A couple of thoughts.

We know very well that low/incomplete AB dosing leads to resistant bacterial strains. We've known this for more than 60 years, long before the advent of genetic study. We can look statistically at the question and come up with very good data on which to base theraputic decisions. All medical and veterinary associations have been cautioning practitioners regarding over-prescribing/low-incomplete dosing for years. The point here is that scientific certainty cannot by definition be achieved. We have to make reasonable decisions based on reasonable data. Thus far we have.

I've seen no valid evidence (and I've looked hard) for cross-species resistance transfer. In fact, from what I've learned, all such published data has later been refuted through refined experimentation.

There's no doubt that AB's have been and continue to be widely misused in human medical practice.

However, there is no evidence of widespread misuse in the veterinary/food animal sector, unless the working definition of misuse includes "don't agree with."

In the very few AB's which are labeled for both human/vet use, non-labeled use is strictly forbidden and harshly enforced. In fact, several hundred DVM's lost licensing for misuse of Baytril several years ago.

Feed additive antibiotics are by law prescription drugs to be administered only by or under the direct supervision of a licensed veterinarian.

Ionophores, which are not antibiotics, are used as rate of gain adjuncts and are approved as such by the FDA. This class of additive effectively treats liver abscess and parasitic gut infestations such as coccidiosis. Rate of gain increases appear to be directly related to treating sublcinical infestations which are present in nearly all livestock (and wildlife).

I don't find the "we shouldn't do anything unless we know everything" argument compelling. So far as I've been able to determine, the very best data available (from both research institutions and pharmaceutical companies) do not show cross-species resistance transfer, nor do they show an increasing resistance trend in humans. The rate of resistance seems to be falling in fact.

I do appreciate your thoughtful response, though, particularly as it reveals a lack of completeness in my argument. Stay tuned to see a better crafted piece.

Thanks again and I do mean thanks. I treasure our acquaintance and your opinion.

K said...

(Ha! Blogger tried to lose my comment again, but I was ready this time! I copied it into my clipboard before I tried to publish!)

Um, Shaun, if they kill bacteria, ionophones are antibiotics. :-)

Has the dose and efficacy of ionophones remained consistent over the years? It seems incredible that an antibiotic could hold up for that long with consistent use. I've seen articles that reference the fact that bacteria do become resistant by adding a type of shielding to their cell membranes that block the ionophones from getting in.

You mention that ionophones are used to treat specific infections, but what I've been able to find said that they are primarily used to inhibit a type of bacteria that will suck some of the energy out of feed before the cattle have a chance to get to it, thus allowing the cattle to harvest more energy from each unit of feed.

Are ionophores the only antibiotic used as a feed additive?

I still contend that there is a general mindset in our society that antibiotics are no big deal. That is slowly changing. (Although not so much in other countries. China and India scare the bejeebers out of me.)

BTW, don't know if ionophone gene resistance specifically will transfer, but bacteria do trade genes.

Do a search on "horizontal gene transfer." Bacteria are genetically engineering themselves all the time. :-)

Here's one layperson article written by a science blogger I trust: http://blogs.discovermagazine.com/notrocketscience/2010/12/13/%E2%80%98friendly%E2%80%99-genes-are-more-likely-to-be-passed-around/

(ps-I enjoy discussions with someone who is thoughtful and doesn't go all "entrenched" on me.)

Prairieadventure said...

Part one...

One of the bestest things about science is uncertainty. But for folks who haven't been able to come to terms with it in the physical realm, uncertainty is frightening.

So regarding the definition of antibiotic, I'll digress for a few paragraphs.

When we're looking scientifically at the problem, uncertainty should force our thinking into a more rigorous channel. And it does so very much when we come to the seemingly simple problem of defining terms such as antibiotic. I concede the point that ionophores seem to kill bacteria. However, their mechanism of action seems (to me at least) to be sufficiently different than that of more classic antibiotics to merit placing them in a slightly different class. Here again uncertainty raises its ugly/beautiful head. If you read the PDR entry for any antibiotic, the first line of the activity paragraph states: "The precise mechanism of action in this drug is unknown, however, it is thought that..."

So the problem in such a simple thing as defining the term is quite hard. Bacteriostats such as iodine and even sunlight could be classed antibiotic under a broad definition, yet they are never prescribed for parenteral or oral use to fight acute or chronic bacterial infection.

The very nature of defining terms relies on the use of precise language and that all parties to the discussion understand the scientific method and its limitations. The fact that basic scientific literacy is flagging in the US makes it tough for anyone to have a "lay" discussion of science. This is where I fear some of the argument gets of track in general, and why science writers and journalists have a tough job when it comes to adequately covering the topic.

To be continued...

Prairieadventure said...

Part two...

Having said that, specifically to your points.

To my knowledge, ionophore feed additives have only been commercially available for 20-30 years. In that time, I'm not aware of increased dosing or decreased efficacy. On our backgrounding operation, we've used the same supplement (protein/Bovatec (lasalocid)) for about 20 years. Same formulation/rate and statistically the same efficacy.

I'd like to see the studies which show development of ionophore resistance. I'll keep looking for them. I've seen some lay papers describing the effect, yet when I read the actual study referenced the results are at best limited and inconclusive.

Could such resistance be occurring? Absolutely. I agree completely that compensatory mutation is the norm in life, rather than the exception. However, I wonder if ionophores don't act in such a basic way (carrying or channeling ions across/through cell membranes, which the cells also must do for themselves to survive) that "resisting" them would be fatal to the cell. Speculation, of course.

Regarding inhibition of gut bacteria, this seems to be true also, however only on a limited and brief basis as the ruminant gut switches from cellulose to starch digestive regimes. As I understand it, the bacteriostatic action seems to knock both starch and cellulose eating bugs back enough to allow the starch bugs to proliferate more quickly in the new high (relatively) starch environment. The dose is held low enough to allow both types to survive, because both are needed. Ruminants must digest high cellulose diets to function; starch is increased in the feedlot but never replaces cellulose at more than a 10 percent dry matter rate. The driving force behind increased feed efficiency/rate of gain is profit, of course. Producers make more money when their animals grow faster, so long as the cost of feed additives does not exceed the profit realized. Nothing fundamentally wrong with increasing profit. However, profit is measured in more than money. Producers have a vested interest in the health of both their animals and their customers. Despite widespread reporting to the contrary, only a vanishingly small number of farmers/ranchers would knowingly allow potential human harm.

Other antibiotics are used as feed additives, however, to my knowledge they are used in only specific cases to actively treat acute disease or prophylactically in specific high stress situations (feedlot intake, poultry hatch, etc.) These antibiotic feeds are classed as vererinary medications and may only be legally used by or under the direct supervision of a veterinarian. This is not to say that they aren't heavily used, however there is a good check/balance system in place.

On a slight tangent, a factor which mitigates potential cross-species resistance transfer is the short lifespan of food animals and the limited contact they have with humans. Also, by law, each veterinary antibiotic has a pre-slaughter withdrawal period to ensure residual AB's are not present in food.

I agree that antibiotics are important. They are over prescribed and poorly dosed in humans. In my opinion, they shouldn't be used as a crutch. When possible, a more holistic approach should be taken. Healthy, non-immunocompromised humans are generally fitted with everything they need to fight infection. AB's should be used to save lives, not to ease unpleasant symptoms.

One more tangent. The real breeding ground for antibiotic resistance is in hospitals and physicians offices. Those places are quite dangerous in the sense that individuals are likely to be exposed to far more nasty bugs there than in any other place.

This continues to be a very enjoyable discussion. Thanks again!

K said...

I wanted to post a link to this monster blog post, since it's a pretty interesting journey to the idea that microbial ecology is important for health:
http://blogs.discovermagazine.com/loom/2011/03/31/the-human-lake/?utm_source=twitterfeed&utm_medium=twitter&utm_campaign=Feed%3A+Loom+%28The+Loom%29

And another link right off the bat, which educated me a bit on ionophones. Such a cool mechanism - kill bacteria by making them furiously pump ions and drain their energy stores!
http://www.ncbi.nlm.nih.gov/pubmed/12697342

On to a couple of thoughts:

"Despite widespread reporting to the contrary, only a vanishingly small number of farmers/ranchers would knowingly allow potential human harm."

Very true. From my experience, many farmers/ranchers are better environmentalists than most urban dwellers. But as with many broad-scale issues, there are problems of incremental contributions.

Which individual farmer is responsible for the nutrient loading leading to Gulf of Mexico hypoxia? There isn't one. It's the incremental actions of thousands of farmers (and lawn-loving suburbanites) in dozens of states.

You're right that the scariest place to be, bacteriologically speaking, is a hospital.

You could think of a hospital as the mouth of a river, with many sources of bacteria leading into it, with each bacterial strain having the capacity to add something new to the mix in terms of antibiotic resistance.

If there are antibiotics that are used on a regular basis prophylactically in high-stress situations (feedlot intake, poultry hatch), it seems to me that there would be some opportunity for antibiotic resistance genes to proliferate.

True, food animals have a short lifespan and have limited contact with people, but there is still contact. There are the workers in the facility. And there are instances of improper manure application to vegetable and fruit crop fields where human illness has resulted.

I don't have a good grasp on how many different classes of antibiotics there are, or what the relative threat agricultural use of antibiotics poses versus the heretofore willy-nilly use of antibiotics in human medicine. But I guess the question developing in my mind now is if widespread prophylactic antibiotic use in a particular industry could be contributing to the river of resistant bugs flowing to hospitals, but it's a "minor stream," relatively speaking, is it worth stopping that particular flow when floodwaters (human use of antibiotics) are coming in from all sides?

Bleh. Sometimes, I just need to stop thinking about the future. Too depressing.

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