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roundtable: the evolving enemy Watch Show 4:
"The Evolutionary Arms Race"
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How concerned should we be about becoming infected with resistant bacteria from foods like chicken, beef, and even aqua-cultured fish that may have been grown on diets treated with antibiotics? Will eating less of these foods, perhaps by switching to "organic" chicken, reduce our risk, and do vegetarians have a reduced risk for this reason?
If the use of antibiotics in a widespread fashion at low doses in agriculture, particularly in the raising of animals, is so common and yet so potentially dangerous from the standpoint of evolution of resistance, why is it still the practice? What are the costs and benefits of this practice?
Several people have submitted questions not about antibiotics, but about all of the liquid soaps that are now for sale in supermarkets that are labeled "antibacterial." Do these work like antibiotics in causing further resistance? If so, how, and if not, how is their action on bacteria different than just plain soap?
Americans now seem to be getting fanatic about sterility, and people are trying to raise their children in an almost "germ-free" environment. We have a question from a woman who says that she has several friends, young mothers, generally, who seem to overuse antibacterial products. She asks: Is it not true that the presence of some "germs" in moderation is actually good for the development of our immune system?
In one of the programs in the Evolution broadcast series, there was the story of the leafcutter ants that culture Streptomyces bacteria on their bodies and seem to use those bacteria to apply antibiotics to keep their fungal farms parasite free. This has been inferred to mean that somehow the Streptomyces and the antibiotics they produce have been evolving with the enemy, and this is a kind of use that appears to have been going on for 15 million years without permanent resistance being developed. Is there anything we can do to put ourselves in that situation versus the more static situation we're in now?
Could you give an explicit description of how evolutionary theory informs integrated pest management? I think the cross-fertilization here between bacteria and antibiotic resistance and agricultural pests and insecticide resistance is very interesting, and I don't think many people make that connection.
Some physicians, who are quite impassioned, say they would like to prescribe fewer antibiotics, but their patients demand them. Since in effect they cannot be absolutely positive there isn't a bacterium involved, when, say, a parent brings in a young child who is ill, and they can't be absolutely certain that there won't be bacterial complications as a result of a viral illness, they would like to know how the public will be educated and who is going to take on the job, so that patients will basically get off the doctors' backs and let their colds run their course.
Another part of that question is that doctors are afraid of being sued if they don't prescribe an antibiotic and a bacterial infection does develop. So from the medical perspective of overuse of antibiotics, how might we address this basic problem in the interface between healthcare providers and the consuming public?
   

 

Q: Several people have submitted questions not about antibiotics, but about all of the liquid soaps that are now for sale in supermarkets that are labeled "antibacterial." Do these work like antibiotics in causing further resistance? If so, how, and if not, how is their action on bacteria different than just plain soap?
Panelist Responses: < back to intro page
Stuart Levy
I can take the initial stab at this, because in my laboratory here at Tufts we've actually been asked to look into this question. The number of these kinds of products has escalated from 1995 to the present day. Our estimate in '95 was about 20-odd antibacterial-containing products, and today we have over 700.

Now, there are two kinds of chemicals that are in these antibacterial products. Some are rapid-acting and they don't leave anything where they were before. Chlorinated products, alcohols, and peroxides do their job immediately, they dry up, they dissipate, and the environment is effectively cleaned. Not totally sterilized, but these products are certainly able -- for instance, in a kitchen -- to clean up an area where you think there might be some harmful bacteria. But once they do their job, the surface is left for the good bacteria in your homes and on your skin to take over and reestablish what we call a normal bacterial community.

Then there are the products that we use successfully in the hospital that are chemically derived. They're used for minutes, not seconds, at a time, and often they leave a residue on your hands, on the counters, to give you that added protection for the next several hours. You get a benefit from that in the particular hospital environment where the protection is needed. This is not needed in the home. And in fact, of the products that are sold over the counter for household use, there has not been a single one which has shown a benefit -- or more benefit than just the soap and water that is in it, which is to wash off all the germs and send them down the sink.

That's a critical point. If there is no recognized benefit, then should we look at what are the potential downsides of this use, that is, the harm? Well, in my laboratory we showed that one of the most important chemical additives, a drug called triclosan, has a target in the bacterium, a single site which it sees and inhibits, and that's what antibiotics do. So in fact, this is not acting like alcohol or bleach, something that just destroys everything in the bacterium; instead, it actually seeks out one particular protein which is involved in making the cell wall and stops it so that the cell cannot make its cell wall and can't multiply and therefore stops growing.

But mutants in that target site occur rather quickly, so that today there are mutants being recognized in many different organisms that are resistant to this product. These have been generally found in hospitals, and have been controlled. But we don't know what the extent is going to be, now that literally every house in the United States, Europe, and elsewhere is now using these products in a casual way, in exactly the way that causes resistance to emerge -- in less-than-effective doses, because they get diluted down on the counters, on your hands, and many, many, many times more frequently than the isolated uses we make of them in designated areas of the hospital.

So you have resistant mutants that can occur, and what we've also discovered is that there are pumps that pump these antiseptics and disinfectants out of the cell which also pump out antibiotics. And so if you select these pump mutants, so to speak, these bacteria that overexpress their pumps, you get bacteria that are resistant not only to the antiseptic or the disinfectant chemical, but also to antibiotics.

So you get a double problem by the use of antibacterials. And what concerns many of us is that the antibacterial-containing materials are being used in homes with the idea that they're a safeguard -- there's no evidence that they are -- and used in a very casual way where their antimicrobial activity is not at all effective, and basically what's happening is they're being left around to do nothing more than aid in the selection of resistant bacteria.
Tamar Barlam
I completely agree they haven't shown a real benefit. But I just wanted to make a really quick point, which is there's a potential problem, from the consumer point of view, which is actually also true for antibiotic-free meat: It's sometimes hard to find products that don't have these antibacterials, and I think that that's a very disturbing trend. So we're not even giving consumers the choices anymore to avoid antibacterials when they want to, with certain products.
Stephen Palumbi
I think what this points up, though, is that this is a situation very similar to the situation of the advent of antibiotics in medicine in the mid 1930s and '40s, where a new approach or a new use of chemicals begins to catch on, and very quickly we use these chemicals on an industrial scale over a wide area. So it isn't just that antibiotic resistance is happening in one place, on one counter, but it's happening consistently with the same chemicals across the entire country. That huge amount of selection pressure then can lead to large problems like we have seen in the past for the evolution of antibiotic resistance in medical cases. So we're doing the same thing again -- that is, using one chemical strategy to excess -- and that huge selective pressure is going to have an evolutionary result.
George Beran
You're raising a significant issue here. The meat industry has been really hearing this, and the antibacterials that are used in the meat industry, in the packing plants and processing, and in washing meat and entire carcasses, have been and are those which are rapid-action and do not leave a residue. And I think it very important that those antibacterials which have the residue and the longer action should not be used in washing meat, and that should include in industry and in the home. I think that's a very important point, and we have been cognizant of this and are on the right track, but it needs to be continually emphasized.
Stuart Levy
I'm delighted to hear that from you, George, and I'm also delighted to hear about the packaging use in the animal industry, because I think it is critical. Stephen's point is, unfortunately, not accepted by those who are waiting for the event to occur before they see that this is a problem. I would hope that viewers of this program can't help but see that overuse in homes all over the country is going to have an evolutionary effect, with the propagation of bacteria and other microbes that are resistant to these chemicals, and possibly also to antibiotics, based on what we see in the laboratory. We have the basis for that.

But unfortunately what we hear is "we don't see a problem yet." Well, I can say that we've seen the problem in certain hospital settings now that we've been asked to look for it. No one ever looked for triclosan resistance in a hospital before, because the bacteria had other resistances as well. Well, it turns out that they are cross-resistant to triclosan and to antibiotics. Which was the selecting factor?

Well, it's hard to tell, but do we really want to wait to see evolution at work again in the home with the propagation of new, resistant forms of bacteria, or do we want to step back and say, Hey, this is not a good idea. Homes don't need these products. You're not getting any better protection. Let's reserve these products for where they should best be used -- that is, to protect the vulnerable patient, used in high quantities that will work, and keep them reserved. But I'm really very disturbed that the message that massive use is going to make a change is not accepted, and the critics are saying, We don't see a problem, so what's all this hullabaloo?
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