DSCN2864

A pig flying at the Minnesota state fair. Picture by TCS.

I’ve been involved in a few discussions of late on science-based sites around yon web on antibiotic resistance and agriculture–specifically, the campaign to get fast food giant Subway to stop using meat raised on antibiotics, and a graphic by CommonGround using Animal Health Institute data, suggesting that agricultural animals aren’t an important source of resistant bacteria. Discussing these topics has shown me there’s a lot of misunderstanding of issues in antibiotic resistance, even among those who consider themselves pretty science-savvy.

I think this is partly an issue of, perhaps, hating to agree with one’s “enemy.” Vani Hari, the “Food Babe,” recently also plugged the Subway campaign, perhaps making skeptics now skeptical of the issue of antibiotics and agriculture? Believe me, I am the farthest thing from a “Food Babe” fan and have criticized her many times on my Facebook page, but unlike her ill-advised and unscientific campaigns against things like fake pumpkin flavoring in coffee or “yoga mat” chemicals in Subway bread, this is one issue that actually has scientific support–stopped clocks and all that. Nevertheless, I think some people get bogged down in a lot of exaggeration or misinformation on the topic.

So, some thoughts. Please note that in many cases, my comments will be an over-simplification of a more complex problem, but I’ll try to include nuance when I can (without completely clouding the issue).

First–why is antibiotic resistance an issue?

Since the development of penicillin, we have been in an ongoing “war” with the bacteria that make us ill. Almost as quickly as antibiotics are used, bacteria are capable of developing or acquiring resistance to them. These resistance genes are often present on transmissible pieces of DNA–plasmids, transposons, phage–which allow them to move between bacterial cells, even those of completely different species, and spread that resistance. So, once it emerges, resistance is very difficult to keep under control. As such, much better to work to prevent this emergence, and to provide conditions where resistant bacteria don’t encounter selection pressures to maintain resistance genes (1).

In our 75-ish years of using antibiotics to treat infections, we’ve increasingly found ourselves losing this war. As bacterial species have evolved resistance to our drugs, we keep coming back with either brand-new drugs in different classes of antibiotics, or we’ve made slight tweaks to existing drugs so that they can escape the mechanisms bacteria use to get around them. And they’re killing us. In the US alone, antibiotic-resistant infections cause about 2 million infections per year, and about 23,000 deaths due to these infections–plus tens of thousands of additional deaths from diseases that are complicated by antibiotic-resistant infections. They cost at least $20 billion per year.

But we’re running out of these drugs. And where do the vast majority come from in any case? Other microbes–fungi, other bacterial species–so in some cases, that means there are also pre-existing resistance mechanisms to even new drugs, just waiting to spread. It’s so bad right now that even the WHO has sounded the alarm, warning of the potential for a “post-antibiotic era.”

This is some serious shit.

Where does resistance come from?

Resistant bacteria can be bred anytime an antibiotic is used. As such, researchers in the field tend to focus on two large areas: use of antibiotics in human medicine, and in animal husbandry. Human medicine is probably pretty obvious: humans get drugs to treat infections in hospital and outpatient settings, and in some cases, to protect against infection if a person is exposed to an organism–think of all the prophylactic doses of ciprofloxacin given out after the 2001 anthrax attacks, for example.

In human medicine, there is still much debate about 1) the proper dosing of many types of antibiotics–what is the optimal length of time to take them to ensure a cure, but also reduce the chance of incubating resistant organisms? This is an active area of research; and 2) when it is proper to prescribe antibiotics, period. For instance, ear infections. These cause many sleepless nights for parents, a lot of time off work and school, and many trips to clinics to get checked out. But do all kids who have an ear infection need antibiotics? Probably not. A recent study found that “watchful waiting” as an alternative to immediate prescription of antibiotics worked about as well as drug treatment for nonsevere ear infections in children–one data point among many that antibiotics are probably over-used in human medicine, and particularly for children. So this is one big area of interest and research (among many in human health) when it comes to trying to curb antibiotic use and employ the best practices of “judicious use” of antibiotics.

Another big area of use is agriculture (2). Just as in humans, antibiotics in ag can be used for treatment of sick animals, which is completely justifiable and accepted–but there are many divergences as well. For one, animals are often treated as a herd–if a certain threshold of animals in a population become ill, all will be treated in order to prevent an even worse outbreak of disease in a herd. Two, antibiotics can be, and frequently are, used prophylactically, before any disease is present–for example, at times when the producer historically has seen disease outbreaks in the herd, such as when animals are moved from one place to another (moving baby pigs from a nursery facility to a grower farm, as one example). Third, they can be used for growth promotion purposes–to make animals fatten up to market weight more quickly.  The latter is, by far, the most contentious use, and the “low hanging fruit” that is often targeted for elimination.

From practically the beginning of this practice, there were people who spoke out against it, suggesting it was a bad idea, and that the use of these antibiotics in agriculture could lead to resistance which could affect human health. A pair of publications by Stuart Levy et al. in 1976 demonstrated this was more than a theoretical concern, and that antibiotic-resistant E. coli were indeed generated on farms using antibiotics, and transferred to farmers working there. Since this time, literally thousands of publications on this topic have demonstrated the same thing, examining different exposures, antibiotics, and bacterial species. There’s no doubt, scientifically, that use of antibiotics in agriculture causes the evolution and spread of resistance into human populations.

Why care about antibiotic use in agriculture?

A quick clarification that’s a common point of confusion–I’m not discussing antibiotic *residues* in meat products as a result of antibiotic use in ag (see, for example, the infographic linked above). In theory, antibiotic residues should not be an issue, because all drugs have a withdrawal period that farmers are supposed to adhere to prior to sending animals off to slaughter. These guidelines were developed so that antibiotics will not show up in an animal’s meat or milk. The real issue of concern for public health are the resistant bacteria, which *can* be transmitted via these routes.

Agriculture comes up many times for a few reasons. First, because people have the potential to be exposed to antibiotic-resistant bacteria that originate on farms via food products that they eat or handle. Everybody eats, and even vegetarians aren’t completely protected from antibiotic use on farms (I’ll get into this below). So even if you’re far removed from farmland, you may be exposed to bacteria incubating there via your turkey dinner or hamburger.

Second, because the vast majority of antibiotic use, by weight, occurs on farms–and many of these are the very same antibiotics used in human medicine (penicillins, tetracyclines, macrolides). It’s historically been very difficult to get good numbers on this use, so you may have seen numbers as high as 80% of all antibiotic use in the U.S. occurs on farms. A better number is probably 70% (described here by Politifact), which excludes a type of antibiotic called ionophores–these aren’t used in human medicine (3). So a great deal of selection for resistance is taking place on farms, but has the potential to spread into households across the country–and almost certainly has. Recent studies have demonstrated also that resistant infections transmitted through food don’t always stay in your gut–they can also cause serious urinary tract infections and even sepsis. Studies from my lab and others (4) examining S. aureus have identified livestock as a reservoir for various types of this bacterium–including methicillin-resistant subtypes.

How does antibiotic resistance spread?

In sum–in a lot of different ways. Resistant bacteria, and/or their resistance genes, can enter our environment–our water, our air, our homes via meat products, our schools via asymptomatic colonization of students and teachers–just about anywhere bacteria can go, resistance genes will tag along. Kalliopi Monoyios created this schematic for the above-mentioned paper I wrote earlier this year on livestock-associated Staphyloccocus aureus and its spread, but it really holds for just about any antibiotic-resistant bacterium out there:

And as I noted above, once it’s out there, it’s hard to put the genie back in the bottle. And it can spread in such a multitude of different ways that it complicates tracking of these organisms, and makes it practically impossible to trace farm-origin bacteria back to their host animals. Instead, we have to rely on studies of meat, farmers, water, soil, air, and people living near farms in order to make connections back to these animals.

And this is where even vegetarians aren’t “safe” from these organisms. What happens to much of the manure generated on industrial farms? It’s used as fertilizer on crops, bringing resistant bacteria and resistance genes along with it, as well as into our air when manure is aerosolized (as it is in some, but not all, crop applications) and into our soil and water–and as noted below, antibiotics themselves can also be used in horticulture as well.

So isn’t something being done about this? Why are we bothering with this anymore?

Kind of, but it’s not enough. Scientists and advocates have been trying to do something about this topic since at least 1969, when the UK’s Swann report on the use of Antibiotics in Animal Husbandry and Veterinary Medicine was released. As noted here:

One of its recommendations was that the only antimicrobials that should be permitted as growth promotants in animals were those that were not depended on for therapy in humans or whose use was not likely to lead to resistance to antimicrobials that were important for treating humans.

And some baby steps have been made previously, restricting use of some important types of antibiotics. More recently in the U.S., Federal Guidelines 209 and 213 were adopted in order to reduce the use of what have been deemed “medically-important” antibiotics in the livestock industry. These are a good step forward, but truthfully are only baby steps. They apply only to the use of growth-promotant antibiotics (those for “production use” as noted in the documents), and not other uses including prophylaxis. There also is no mechanism for monitoring or policing individuals who may continue to use these in violation of the guidelines–they have “no teeth.” As such, there’s concern that use for growth promotion will merely be re-labeled as use for prophylaxis.

Further, even now, we still have no data on the breakdown of antibiotic use in different species. We know over 32 million pounds were used in livestock in 2013, but with no clue how much of that was in pigs versus cattle, etc.

We do know that animals can be raised using lower levels of antibiotics. The European Union has not allowed growth promotant antibiotics since 2006. You’ll read different reports of how successful that has been (or not); this NPR article has a balanced review. What’s pretty well agreed-upon is that, to make such a ban successful, you need good regulation and a change in farming practices. Neither of these will be in place in the U.S. when the new guidance mechanisms go into place next year–so will this really benefit public health? Uncertain. We need more.

So this brings me back to Subway (and McDonald’s, and Chipotle, and other giants that have pledged to reduce use of antibiotics in the animals they buy). Whatever large companies do, consumers are demonstrating that they hold cards to push this issue forward–much faster than the FDA has been able to do (remember, it took them 40 freaking years just to get these voluntary guidelines in place). Buying USDA-certified organic or meat labeled “raised without antibiotics” is no 100% guarantee that you’ll have antibiotic-resistant-bacteria-free meat products, unfortunately, because contamination can be introduced during slaughter, packing, or handling–but in on-farm studies of animals, farmers, and farm environment, studies have typically found reduced levels of antibiotic-resistant bacteria on organic/antibiotic-free farms than their “conventional” counterparts (one example here, looking at farms that were transitioning to organic poultry farming).

Nothing is perfect, and biology is messy. Sometimes reducing antibiotic use takes a long time to have an impact, because resistance genes aren’t always quickly lost from a population even when the antibiotics have been removed. Sometimes a change may be seen in the bacteria animals are carrying, but it takes longer for human bacterial populations to change. No one is expecting miracles, or a move to more animals raised antibiotic-free to be a cure-all. And it’s not possible to raise every animal as antibiotic-free in any case; sick animals need to be treated, and even on antibiotic-free farms, there is often some low level of antibiotic use for therapeutic purposes. (These treated animals are then supposed to be marked and cannot be sold as “antibiotic-free”). But reducing the levels of unnecessary antibiotics in animal husbandry, in conjunction with programs promoting judicious use of antibiotics in human health, is a necessary step. We’ve waited too long already to take it.

Footnotes:

(1) Though we know that, in some cases, resistance genes can remain in a population even in the absence of direct selection pressures–or they may be on a cassette with other resistance genes, so by using any one of those selective agents, you’re selecting for maintenance of the entire cassette.

(2) I’ve chosen to focus on use in humans & animal husbandry, but antibiotics are also used in companion animal veterinary medicine and even for aquaculture and horticulture (such as for prevention of disease in fruit trees). The use in these fields is considerably smaller than in human medicine and livestock, but these are also active areas of research and investigation.

(3) This doesn’t necessarily mean they don’t lead to resistance, though. In theory, ionophores can act just like other antibiotics and co-select for resistance genes to other, human-use antibiotics, so their use may still contribute to the antibiotic resistance problem. Studies from my lab and others have shown that the use of zinc, for instance–an antimicrobial metal used as a dietary supplement on some pig farms, can co-select for antibiotic resistance. In our case, for methicillin-resistant S. aureus.

(4) See many more of my publications here, or a Nature profile about some of my work here.

 

Comments

  1. #1 C Cordova
    September 10, 2015

    Really great blog. Thanks for you work and your communication on this issue. Nicely done!

  2. #2 G
    September 10, 2015

    Fantastic article, Tara, and it should be widely read.

    What to do about Food Babe: “Food Babe’s comments in support of reducing nonessential use of agricultural antibiotics are convergent with widely-accepted conclusions of mainstream science.” The framing is: she agrees with us, not vice-versa. (And frankly if she can get a large flock of wooskis onboard for this, maybe some of them will stick around for more science. One can hope…)

    Consumer demand does have the potential to bring change ahead of government regulation. This is something in which we can all participate, by simply asking for antibiotic-free meat wherever we shop. Even folks on a poverty budget can afford this by buying a little less meat and substituting other foods. Shifting demand by even a few percentage points could be enough to start a competitive trend that results in major gains: by analogy consider the increase in recycled paper content of various kinds of household paper products over the years.

    Re. meat producers objecting to regulation: if all of them are held to the same regulatory standards, and the regs are enforced, then the playing field has not been tilted: it’s been shifted equally for all. Thus their competitive situation does not change compared to what it is before the regulations are enacted. This is an effective counterpoint to their complaints.

    Eventually we’ll have inexpensive “vat meat,” that should hopefully put an end to a wide range of undesirable agricultural practices.

  3. #3 maryn
    September 11, 2015

    This is a great explainer, I’ll be happy to push it along! A pity about the Food Babe and the Subway campaign; a good bet that, if Subway does what campaigners want, she’ll claim she made it happen, just as she claimed she was responsible for the Chick-fil-A decision. (Not.)

  4. #4 Tara C. Smith
    September 11, 2015

    G, re regulation–that’s a big “if” (several, in fact). I think a big reason the voluntary guidance documents got buy-in from industry was because they lack real enforcement, but at the same time allow for the companies to say “see, we’re helping!”

    Maryn, thanks! And of course she will–it’s all her “army” that do these things, right? Not the people who have been working on it behind the scenes with less fanfare for years before she ever came onto the scene…

  5. #5 G
    September 11, 2015

    Tara @ 4: Thanks; and clearly “voluntary guidance” has not worked, so it’s time for all of us to pester our elected officials until they take decisive action. Agreed, “several IFs don’t make a THUS,” but as all of this operates in the realm of politics, part of our task is the use of rhetoric. Apparently I didn’t do such a good job of it there, but these kinds of public discussions are useful for critique & refining our rhetorical approaches.

    Re. Food Babe again, she can take all the credit she wants, because in the bigger picture she’s small beans compared to public health scientists who have real credibility based on real achievements.

  6. #6 Anya Vanecek
    United States
    September 11, 2015

    Tara, thank you for one of the best explainers I’ve ever read on antibiotics resistance, and something we need more of. I am looking forward to sharing this with U.S. PIRG followers and members, who have been working hard to help fight this problem and who will no doubt appreciate this post at least as much as I do.

    There’s one point, however, that I think needs some clarity. It’s important to recognize that Subway’s statement is not a commitment, and anything short of a concrete plan to switch to meat raised without routine antibiotics will have little, if any, real impact. We saw this in nearly a decade of McDonald’s saying it supported the idea of antibiotic-free meat, to no avail. Then, weeks after they made a firm commitment, with a timeline and plan of action, we saw Tysons and a number of others, start to follow suit. This was major. Subway is not quite there.

  7. […] Antibiotic resistance: myths and misunderstandings As such, much better to work to prevent this emergence, and to provide conditions where resistant bacteria don't encounter selection pressures to maintain resistance genes (1). …. Neither of these will be in place in the U.S. when the new guidance … Read more on ScienceBlogs (blog) […]

  8. […] resistance building up from the frequent use of antibiotics. (You can read more about that here.) Of course, this is something that should concern all of us, and we should all consider ways we […]

  9. […] resistance: myths and misunderstandings #longread scienceblogs.com/aetiology/2015… 1 min […]

  10. […] Exceptional explainer about antibiotic resistant microbes, by Tara […]

  11. […] Exceptional explainer about antibiotic resistant microbes, by Tara […]

  12. #12 Rex Peterson
    Nebraska Panhandle
    September 24, 2015

    Is the appropriate conclusion for the study from Levy that tetracycline resistant bacteria is a consequence of tet feed or is the appropriate conclusion that traces of tet feed in the atmosphere are sufficient to kill non resistant bacteria. The reduced completion would result in more favorable conditions for the tetracycline resistant bacteria growth. Obviously, the condition was favorable to chicken production or the feed would not have been marketable.

  13. #13 Tara C Smith
    September 24, 2015

    It’s a consequence of using feed containing the antibiotic, which selects for the resistant bacteria.

  14. […] resistance building up from the frequent use of antibiotics. (You can read more about that here.) Of course, this is something that should concern all of us, and we should all consider ways we […]

  15. #15 Brittany N.
    United States
    October 10, 2015

    Thank you for the work you put into this article! It really helped simplify all the parts in the relationship between humans and antibiotics, and the cause and effect. This is the kind of information that needs to be more readily available to the public. I do not think the average person is aware of some of the points you have made here, which I think is another problem in and of itself.

  16. #16 Moderate the Medicine
    Australia
    October 18, 2015

    Fantastic article! It is great to see word about antibiotic resistance spreading. Antibiotic resistance truly is one of the greatest threats to the worlds future health, The guardian recently release an article stating that there could be an additional 6300 deaths per year in the US if the effectiveness of antibiotics drops by only 30%.

    We at Moderate the Medicine (moderatethemedicine.wordpress.com) are also campaigning to promote the responsible usage of antibiotics. We try to present information about antibiotic resistance that is accessible to the general public, with articles like our latest: 7 things you can do to help prevent antibiotic resistance (https://moderatethemedicine.wordpress.com/2015/10/18/7-things-you-can-do-to-help-prevent-antibiotic-resistance) and topics ranging from the history of antibiotics to the impacts the livestock industry has on antibiotic resistance.

    Thank you for spreading the word

    Stay well.
    Moderate the Medicine.

  17. #17 Molly Klug
    Denver, CO
    November 26, 2015

    This is a great post that is very informative! Antibiotic resistance is a huge issue that is quickly growing, and unfortunately it is not something that very many people know about, or fully understand. I think the great misconception about antibiotics is that it is only taking them unnecessarily or incorrectly that causes resistance, which is not the case. While this is a huge contributor (studies done by the CDC estimate that half of all prescriptions are given incorrectly or unnecessarily), it is not the sole cause. Taking antibiotics in any way, shape, or form helps to contribute to resistance. This is why getting antibiotics out of our food sources, namely livestock, is so important! Thank you for writing about a very important issue and for helping to educate people!

    Molly Klug

  18. #18 Skeptic Scott
    Chicago, IL
    November 27, 2015

    One thing not mentioned here is the massive use of anti-bacterial soaps, everywhere, all the time. When people use soaps that are claimed to kill 99.9% of germs, no one seems to worry about what becomes of the other 0.1% over time.

  19. #19 Louis Wentzel
    Cape Town, South Africa
    December 30, 2015

    An outstanding article.
    I recently wrote my final Life Science exam and in my studying I developed quite an interest in Darwin’s theory of natural selection. This article was very educational in the sense that I now see that there is a fine balance in nature and that it is our responsibility to do our utmost to keep the balance. We are after all part of nature and rely on it for everything.
    Thank you.

  20. […] we have been in an ongoing ‘war’ with the bacteria that make us ill.” And thanks to the overuse of antibiotics in medicine and animal husbandry, we are losing out quickly. Like 20th century climate, 20th century medicine is something we have […]

  21. […] resistance building up from the frequent use of antibiotics. (You can read more about that here.) Of course, this is something that should concern all of us, and we should all consider ways we […]