Bacterial resistance to chronic antibiotics, and why it’s a problem

Unlike climate change, where there’s a large contingent of denialists who spread doubt about the scientific evidence, no one denies that antibiotic resistance is a problem. There is controversy, however, on the question of just how much the widespread use of antibiotics contributes to the problem.

The mechanism is not in dispute: If you expose bacteria to antibiotics, they will mutate to become resistant. But “overuse” of antibiotics is not the only thing that creates antibiotic resistance. Is there irrefutable scientific evidence that the overuse of antibiotics in raising livestock, for example, is harmful to human health? It’s not easy to prove direct cause and effect. If you feed a pig a steady diet of antibiotics, can you irrefutably prove that this results in the illness or death of someone who later eats that pig?

Follow the money

The speed with which we address the increasingly urgent problem of antibiotic resistance will depend on financial interests, not just scientific evidence or common sense. Just as with climate change, we can follow the money to identify the opponents. Who has a financial interest in convincing the public — and in turn politicians — that the overuse of antibiotics is not a problem?

It’s not the medical profession, which understands that overprescribing antibiotics contributes to the increase in antibiotic resistant bacteria. The financial interests of doctors are a little complex here. Unfortunately, because the public is not well educated about the subject, doctors find they need to satisfy the demands of their patients by offering prescriptions. Otherwise patients would simply take their business elsewhere. It takes time for doctors to educate their patients, and today’s doctors are very short of time. This is not sufficient grounds, however, to say that doctors have a financial incentive to overprescribe. Although doctors practicing today have no personal memory of the pre-antibiotic era, they are certainly among the first to appreciate that practicing medicine would become a nightmare without antibiotics.

Pharmaceutical companies aren’t really the problem either, since they’re not interested in selling or developing antibiotics. These drugs are not sufficiently profitable. This is a problem in itself, since the world desperately needs new antibiotics. Although drug companies might like to see more antibiotics prescribed and sold, this is such a small part of their overall business that there’s little motivation for them to question the dangers of overuse.

Where we can expect pushback is from the agricultural industry. This is a battle that’s just beginning to heat up. Katie Couric did a story on the CBS Evening News in February that got some attention: “Animal Antibiotic Overuse Hurting Humans?”

Well, maybe it’s a problem, but maybe it’s not

Publications that serve the livestock community – the beef, chicken, and hog industry – have been following the issue closely. It was interesting to see what a balanced approach Voice of America took on the issue.

Over-use in animal husbandry is not the only source of antibiotic resistance. Health experts point to doctors over-prescribing antibiotics, and patients misusing them, as another part of the problem.

And the growth-promoter ban [a Danish ban on drugs used as growth promoters] does not appear to have made much difference in the overall rates of resistant infections in people, says Rich Carnevale with the U.S. industry-sponsored Animal Health Institute. He says Denmark may have over-reacted.

He says, “They saw resistance. They said, ‘Well, it could be due to use of drugs in animals. And certainly some of that resistance was. But the real question is, was it harming humans? And to this day, they have not been able to really conclude that it’s actually harming humans.”

This is where opposition to attempts to reduce the use of antibiotics reminds me of those who oppose climate change legislation.

The controversy about the overuse of antibiotics in raising livestock is background for an interesting scientific study that took place in the Galapagos. It looked at the spread of antibiotic resistant strains of bacteria among animals that were totally removed from antibiotics.

Would antibiotic resistance become widespread in the absence of antibiotics?

The immediate motivation for the research was two contradictory studies. In a wooded area of northwest England, researchers had found that wildlife developed antibiotic resistance even though they had not been exposed to antibiotics. This would argue against the idea that antibiotic use in animals should be restricted, since it suggests that antibiotic resistance would develop anyway.

Another study, however, found that wildlife in a remote area of Finland had an almost complete absence of antibiotic resistance. This would argue that resistance could be reduced by restricting antibiotics.

So which was it? How could you design an experiment that controlled possibly confounding factors, such as climate, animal interaction, and human interference?

Coprophagial iguanas

The researchers chose to study a species of iguanas (Conolophus pallidus) on an isolated island (Santa Fe) in the Galapagos . Unlike the English countryside, the island was uninhabited by humans, though tourists made daytime excursions to a restricted area. It offered an example of what life was like in a pre-antibiotic era. This tropical island, which was near the equator, was also unlike the remote area of Finland, where winters were long and cold, the population density of animals was low, and there was limited interaction among animal species.

The island was ideal for the spread of bacteria: It was warm, humid, with constant periods of daylight and high animal density. Plus, juvenile iguanas acquired their intestinal microorganisms through coprophagy (eating feces). This results in bacteria spreading readily throughout the community of iguanas.

This was the perfect setting to test the following: If there are no antibiotics present, and an antibiotic resistant strain of bacteria is present, will it spread throughout the community?

When there’s no chronic antibiotic exposure, resistance doesn’t spread

The researchers discovered that no, it would not spread. A small minority of animals did have bacteria that exhibited resistance – probably acquired from a visiting tourist — but the rest of the community was uncontaminated with these resistant bacteria.

Here’s the conclusion of the study. Let me restate the first sentence in non-academese: Will an antibiotic resistant strain of bacteria spread readily throughout a community if there are no antibiotics present? If so, then this was the ideal situation to observe that happening.

[B]acteria colonizing the gut can easily spread within the reptile community and, if an introduced resistant strain should not need the presence of antibiotics to become widespread, in Santa Fe it would find the optimal conditions for this to occur. In this scenario, the detection of two E. coli isolates with acquired resistance traits of likely human origin as non-dominant microbiota in a small minority of animals, reveals that even highly isolated ecosystems are susceptible to contamination by multiresistant strains. However, in the absence of a chronic antibiotic exposure sustaining resistance, these strains failed to disseminate despite the fact that environmental conditions and animal habits were highly favourable to inter-individual spread, and that contamination from humans to wildlife could recurrently occur at that site. … [L]imited human-driven contamination, in the absence of a chronic antibiotic exposure, is not sufficient for the diffusion of acquired antibiotic resistance in wildlife.

This is not a definitive answer to the question of whether antibiotic use should be reduced or banned in raising livestock. But it certainly does suggest that when antibiotics are not present, antibiotic resistant bacteria do not thrive and spread.

Jan Henderson is a historian of medicine who blogs at The Health Culture.

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