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Antibiotic Resistance: Let’s Change the Way We Understand It

Opinion

In the past few days, there have been two interesting reports on antibiotic resistance. One was released by Consumer Reports entitled, “How Safe Is Your Ground Beef?” The other, much less publicized, was put together by scientists and physicians who work in public health and do know something about antibiotic resistance.

This second report was published in the Morbidity and Mortality Weekly Report (MMWR) and is part of the Grand Rounds by the U.S. Centers for Disease Control and Prevention (CDC). From this second report, I like both the title, “Getting Smart about Antibiotics,” and the fact that the authors present an appalling number of figures pointing out the impact of inappropriate antibiotic use in human medicine.

There is no doubt that the “increasing prevalence of antibiotic-resistant bacteria is one of the most serious threats to public health in the 21st century.” But there is also no doubt that this is a complex issue, and pitting one food system against others will not solve the problem. Blaming the use of antibiotics in medicine versus veterinary medicine will not solve the problem either. But for some reason, the discourse about antibiotics resistance has taken the form of blaming somebody or something.

The study of antibiotic resistance is extremely complex because of the variability in the methods of testing for antibiotic resistance and the temporal and spatial inconsistencies in the results. An example of this variability can be seen in Figure 1 (see graph below) created with the interactive feature from the website of the National Antimicrobial Resistance Monitoring System (NARMS).

Ciprofloxacin-Clindamycin

Footnote Figure 1: Variability by year of ciprofloxacin and clindamycin, two antibiotics that are used mainly in human medicine. The resistance to these antibiotics by Campylobacter jejuni, a common foodborne pathogen, shows a wide variation by year. For some years, there is no clear association of resistance in the strain of C. jejuni collected from humans and the strains collected from foods.

As expected, the article from Consumer Reports was sensationalistic and did exactly that. Yet we should not forget the other reports — those much less publicized but done with scientific rigor — to make us think for a moment about the scope of the problem. I am referring to reports like the one by Jo Handelsman at Yale University and her colleagues highlighting that the use of manure fertilization, or amendment, can lead to a surge of antibiotic-resistant bacteria in the soil that is not related, or independent, of the antibiotic exposure of the animals from which the manure is obtained.

There is no argument against the fact that human activities of all kinds have resulted in the increase of antibiotic use in the past 50 years, with the consequence of selecting for those bacteria that are resistant. These resistant bacteria may have the genetic components to become resistant or have the physiological properties to quickly adapt and become resistant in the presence of antibiotics in the environment. This consequence is not surprising either, as many scientists have been telling us about the issue of antibiotic resistance, and for a long time.

Most recently, bacteria isolates from ancient Arctic soil and from the microbes that are present in the intestinal tract of an isolated, uncontacted indigenous population of Yanomami Amerindians in South America have revealed the presence of antibiotic resistance. So bacteria have been evolving different resistance mechanisms against antibiotics because these bacteria have been competing with each other for resources in the same environment, mainly in the soil, for thousands of years.

These articles that do not get too much attention but provide us with thoughtful insights should be discussed more. That’s why I like the article published in MMWR. The authors offer a sort of “mea culpa,” if you will, but move on to show us figures that are, again, appalling. The fact that we have “142,000 adult emergency visits annually” because of adverse reactions to antibiotics is telling us that maybe the current antibiotics groups may not be the best approach to combat pathogenic bacteria in the long run. Yet, the search for new classes of antibiotics has not been accelerated over the years, and it may have been slowed down in reality. An extensive study by The Pew Charitable Trusts is unambiguous about this trend: There are too few drugs in development to meet current and anticipated patient needs.

The public should be exposed to these types of reports, too — those reports that show us that everybody should share the burden of antibiotic resistance, and we should not just keep finding scapegoats for a problem that will stay here longer if we do not change the way we understand it.

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  • MaryFinelli

    Blaming agribusiness for using immense quantities of antibiotics to cause animals to grow larger faster -and to try to keep them alive in the horrendous, irresponsible conditions to which they are subjected long enough to make it to slaughter, though many don’t even survive that long- is not “scapegoating” it. It is putting blame squarely where it very much belongs. Blame can also be placed on the government for failing to do anything meaningful about it.

    • RoyWillaims

      Mary

      Antibiotics are expensive to purchase and expensive to administer to livestock. No one in the livestock industry wants to be buying and administering antibiotics. There is very little profit to be had in any one animal, and that small profit often gets spread over multiple owners. Whoever puts antibiotics in the animal most likely will not make a profit on that animal. Furthermore, if you own an animal and it dies, you loose money, so you try very hard to keep every animal healthy so that you don’t give it antibiotics and don’t let it die.

      It is incorrect to state that antibiotics make the animals grow larger. Antibiotics reduce the pathogen load on the animal so that it can more nearly reach its full genetic potential. For years cattlemen have tried very hard to prevent illnesses of any kind in their livestock. Unlike in human medicine, in which no treatment is given until the person is rather ill, cattlemen have used antibiotics to knock out “sniffles”, and thus (hopefully) prevent more serious disease.

      The drive to limit antibiotic use in livestock needs to be tempered with an understanding of what such limitation will or will not accomplish, and the impact it will have it terms of increased sickness and suffering in livestock, the resulting increase cost of meat, and the likelihood of the development of new diseases in spite of the limitation in the use of antibiotics. As one with some understanding of the microbiology involved (a bacterial culture can be to develop a resistance in a matter of days in some cases), I am skeptical that any net benefit will be obtained, either in human medicine or in veterinary medicine, by limiting antibiotic use, but each case should be carefully considered. My main fear, perhaps motivated by my own experience, is that mortality will increase as medical providers delay antibiotic treatment to the detriment of the patient (“let’s wait and see if you get over this”). I hope my pessimism is unfounded.

      Yes, the livestock industry uses a lot of antibiotics. Cattle are much, much larger than people, and an effective dose of an antibiotic is much larger for a large steer than it is for a person. But the popular image of farmers running around willy-nilly sticking antibiotics in every animal is a fiction.

      It is also a fiction that a lot of animals die on the way to slaughter. When you see a large group of cattle lying almost on top of each other in a feedlot, that may look “bad”, but that is exactly what cattle do when put on an unfamiliar open range – they feel more secure in a group.

      Cattle are much like us humans: our distant ancestors did not have cars, air conditioned apartments, and did not work in 8 x 8 office cubes or shoulder to shoulder on an assembly line. Today we freak out if someone is “lost” in a wilderness for a day or two, yet all people lived in primitive environments prior to the dawn of civilization in the Fertile Crescent thousands of years ago. Today we pretty much sit on top of each other watching TV or movies, or eating meals in restaurants, and we are OK with that. I will now apply that observation to cattle.

      I have had quite a few pet cows and steers over the years, and I can tell you that cattle are the biggest couch potatoes of all time. They want food and a soft cool place to lie down. They will not graze on pasture if they have an alternative that is fresh, tastes good, and is easy to get. They will crowd into what ever space they can find that is shelter from sunlight, rain, heat and cold – just as people will do (well, skip the sunlight part – cattle are wiser than people about getting out of the sun if they can). After many years of owning cattle as pets and having cattle as “part of the family”, I can tell you that the belief that cattle are “abused” by being kept in barns on in large groups in small spaces is completely misguided – given a choice, that is what cattle will do.

      This article references several very well done investigations into antibiotic resistance; they do not support your claim that the livestock industry is the cause of antibiotic resistance. Using antibiotic resistance as a tool to advance anti-agriculture agendas is a detriment to making thoughtful well informed decisions regarding the handling of the complex issue of antibiotic resistance.

      The optimal answer to the dilemma of antibiotic resistance is the development of new antibiotics. Unfortunately, the regulatory process is so burdensome that only the very largest companies can afford to take a new drug through the decades-long regulatory process. Increasingly, the only drugs being brought to market are drugs that cost tens of thousands of dollars per year or course of treatment, and only work in very small patient populations (because those are the only drugs that will be profitable). Given that antibiotic resistance to many popular antibiotics available today was first observed in some cases only a few years after the introduction of the drug, we should realize that we need to be bringing new antibiotics into use to replace older antibiotics every decade or less (depending on how fast resistance develops).

      To achieve that goal we will need a vastly different regulatory process, a business model that will allow small “start up” companies to bring products all the way from laboratory discovery to product on the drug store shelf without the involvement of multinational corporations, and a public recognition that, like the author of this article stated, we are all in this together.

      Another excellent line of defense is improved (and more) vaccines, but that approach is hampered by unrealistic and irrational demands by regulatory agencies and the public at large for “proof” of very high levels of safety, the resistance of some individuals to accept vaccination at all, and debates over what constitutes proper ethics in drug and vaccine trials.
      As the world becomes ever more crowded, vaccinations and antibiotics will increasingly be required to prevent large scale outbreaks of disease. In many ways, we were lucky that the HIV virus did not spread by wind or casual contact, or it would have likely killed a significant fraction of the world’s population. But it should be a warning to people everywhere of what can happen if we do not develop robust protocols for the rapid development and deployment of novel vaccines and antimicrobials in the face of novel pathogens and global health challenges.

      • “Yes, the livestock industry uses a lot of antibiotics. Cattle are much, much larger than people, and an effective dose of an antibiotic is much larger for a large steer than it is for a person. But the popular image of farmers running around willy-nilly sticking antibiotics in every animal is a fiction.”

        No, this is actually what’s happening: antibiotics are used for prophylactic purposes, which means they’re administered without evidence of injury or disease.

        That would be like you taking your disease-free child into the doctor at the start of the school year, and demanding he or she give your child a dose of antibiotics, “just in case”.

        • Let no good deed go unpunished

          Shelley, a more correct analogy might be…like protecting your pet dog from heartworm by keeping with an approved dosing schedule. But good as it is, that’s only a rough, overly simplistic analogy. Magnitudes better than your cookie-cutter talking points, though. And of course your claim that all antibiotics are used for prophylactic purposes is a calculated untruth. You might be forgiven the hyperbole if you didn’t actually know better. We get it.

          Any attempt to explain the realities to you would be a disappointing waste of time. How did Barney Frank put it?…”like arguing with a dining room table” or some such like.

          • Unless you want to disagree with the CDC, as well as the scientific community, agriculture is using antibiotics for prophylactic reasons. Your saying they’re not doesn’t change the facts.

            Here, reading material

            http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234384/

            Your insulting me just undermines your own credibility, particularly at a site such as Food Safety News. Especially when you comment using a pseudonym.

          • Andre

            Where did she claim “all” antibiotics are used for prophylactic purposes?

            Talk about “calculated untruth.”

  • Mike_Mychajlonka_PhD

    Some years ago, I was a senior scientist with the Warner-Lambert/Parke-Davis pharmaceutical company. I had a special project there, funded by the Vice President for Research to look for elements of a novel regulon my previous academic work had suggested might be in operation in certain pathogenic bacteria. The reason was to identify novel drug targets. To make a long story short, I found what I was looking for. At the request of the legal department, I was in the middle of the background patent search when news came that WL/PD was the subject of a hostile takeover. To defeat this business move, WL/PD fired a whole bunch of people. The rule was “last in, first out.” Having succeeded in my work, I now found myself out of a job. My discoveries were turned over to me, which seemed, at first, like a good thing except that I soon learned this meant that other pharmaceutical companies would not hire me as they now feared that a conflict of interest. WL/PD fought off the first attempt to dismember it but in the process so damaged itself that it was a sitting duck for takeover by Pfizer, who quickly dismembered the company completely. I understand that Pfizer has now pinned its pharmaceutical research hopes on China. Meanwhile, a large collection of academics saw the value (to themselves) of acting like patent trolls. At least one of this number followed me around to any scientific meeting I went to and took copious notes on the work I reported. I later saw that those notes contributed to several claims in a patent I was never part of. Of course, I was never the fool these folks took me for. My central findings, those that tied everything together, were always held back. The trolls had the phenomenology I had publicly reported but not the rationale behind it nor the explanation. So sad. Around this time also, the US Patent Office was told to fund itself. It did so by instituting fees so that today an inventor has no real incentive to patent, unless a market already exists. The current situation is an absolute mess. I wish I could see a path to a speedy resolution. One of the things that sometimes keeps me up a night is wondering how many people have suffered and, of those, how many have died who would not have, had my discoveries been efficiently and fairly implemented, rather than been merely the implements of the greedy.

    • Albert Whinestein

      Did I ever tell you about the time I invented a minivan that was powered exclusively by happy thoughts? No gas or oil required. Just believe hard enough and presto! But long story short just when I was scheduled to go to Washington to be awarded the Congressional Medal of Honor, evil conspirators intervened to block the otherwise world changing means of travel and I was left unemployable again. That’s when I invented a pretty good perpetual motion machine. Much to my dismay that was stopped by corporate greed also…and by discriminatory clerks at the US Patent Office. Now I’m working on a cure for baldness that is a sure fire winner. All top secret this time, of course.

  • Oginikwe

    “can lead to a surge of antibiotic-resistant bacteria in the soil that is not related, or independent, of the antibiotic exposure of the animals from which the manure is obtained.”

    So this is stating that these bacteria developed antibiotic resistance to antibiotics it never met?
    How does that work? Why would bacteria develop a resistance to something not in its environment?

    • Beatrice

      Yeah. Out here in the real world antibiotic resistance seems to be rather more involved than the oversimplified talking points activists choose to believe in. Science is like that. If everything, heck if anything was as simple as your cult believes everything would be unicorns and rainbows all the time. So, please explain why the power of your backward beliefs have not delivered us into this splendid dreamworld by now? You’ve made no progress, so what’s the problem? Conspiracy probably, eh?

      • Oginikwe

        You make many assumptions about my post that are not present. That was a viable question and your snark in response to other people just turns them off. I’m sorry you are so lacking in social skills; I’m sure if you tried, you could actually be a nice person and maybe even, oh, teach someone something like Mr. Edlind.

    • Tom Edlind

      Oginkwe – Good question. Antibiotic resistance may be mediated by specific mutations in the antibiotic target, but more often is mediated by non-specific toxin-resistance mechanisms, particularly so-called multidrug efflux pumps that recognize a spectrum of structurally related molecules and pump them out of the cell. These pumps evolved to protect the organism (dozens present in nearly all species from bacteria to humans) from environmental toxins and metabolic waste products, but some of them just happen to recognize clinically important antibiotics (even man-made ones that the world has never seen before).

      • Oginikwe

        Thank you for your explanation.

  • Basically what you’re saying is: the CAFOs don’t want to change, so invent new drugs.

    • Farmer with a Dell

      We know you are on the dole to bash CAFOs but what do you have against continued development of new and effective pharmaceuticals? Have you no conscience?

      • Exactly what “dole” am I on?

        FSN needs to consider blocking anonymous hit-and-runs. They lower the caliber of the discussion.

  • In all seriousness, no one is using agriculture as a scape goat, but when it comes to antibiotic resistance, we can’t ignore the elephant in the corner.

    We’ve already acknowledged human abuse of antibiotics and, for the most part, hopefully we’re beginning to address the issue. There will always be people in the medical community who prescribe antibiotics for every sniffle, but hopefully the numbers will diminish.

    The same effort does not seem to be happening in agriculture. Instead, those with livestock are encouraged to change, but not given any impetus to do so.

    So the finger of blame naturally starts to drift towards the biggest abuser, and it is agriculture.

    Yes, new antibiotics would be great, but who is to say the agricultural community won’t start abusing them? If we don’t change the culture, all the new drugs will be is just a new source of drugs to abuse.

    • Farmer with a Dell

      “In all seriousness”, you are clueless. Or much, much worse.

      Delighted to hear you have brought abuse of antibiotics in human medicine under perfect control world wide so it is no longer an issue. While you are triumphantly thrusting the finger of blame in our faces you won’t mind if we give you the finger right back, will you?

      • When you sign in with your real name, I’ll treat you as something other than sidewalk gum.