The publication last month of a new report by the Review on Antimicrobial Resistance, commissioned by Prime Minister David Cameron, led to further widespread media coverage of the issue of antibiotic resistance. This latest report focuses specifically on the issue of antibiotic use and overuse in farming. It found “compelling” evidence of a link between veterinary antibiotic use and resistance in human medicine, which the authors said warranted a global reduction in farm antibiotic use. Jim O’Neill, chair of the Review, commented that, “It’s time for policymakers to act on this. We need to radically reduce global use of antibiotics, and to do this we need world leaders to agree to an ambitious target to lower levels, along with restricting the use of antibiotics important to humans.”Antimicrobials in Agriculture and the Environment

One of the review’s most interesting findings, not widely reported, is that it discovered a clear distinction in the scientific literature between the conclusions of academic scientists and those of scientists affiliated to the government or pharmaceutical or animal-health industries. Whereas 72% of papers by academics found evidence of a link between the farm use of antibiotics and resistance in human medicine, this fell to just 26% for government/industry scientists. Furthermore, the majority of studies opposing a reduction of farm antibiotic use were authored by scientists affiliated to either governments or industry.

Industry opposition

The ongoing opposition from some industry members to reducing farm antibiotic use has been illustrated in a recent exchange of letters in the Veterinary Record between David Burch, a leading veterinarian specialising in intensive pig and poultry production, and Richard Young and myself. The SFT reported on the initial letter by David Burch and our first response in an earlier article. The Veterinary Record has now published a further letter from David Burch and another response from us.

David Burch’s initial arguments against further restrictions on farm antibiotic use were twofold: firstly, he claimed that the UK is already a relatively low user of antibiotics per unit of livestock in comparison to countries like Denmark and the Netherlands, and secondly, he suggests there is little evidence that some of the most resistant E. coli bacteria, called ESBL E. coli, are transferring from farm animals to humans, since the strains found in animals and humans tend to be different.

We explained it is only possible to make accurate comparisons between use in different countries if statistics for each farmed species are also taken into account, because there are large differences in usage between species, partly due to the different production systems used. For example, intensively farmed pigs and poultry generally use far more antibiotics than sheep and goats, which tend to be kept more extensively. The UK has a relatively large number of sheep and a relatively small number of pigs, which helps bring its average usage figure down. But when pigs and poultry are looked at separately, antibiotic use in the UK is in fact over three times higher than in countries like Denmark and the Netherlands.

On David Burch’s second point, we referred to a large amount of evidence showing that resistance can transfer from farm animals to humans, for bacteria like salmonella and campylobacter (which cause food poisoning), E. coli (which cause urinary-tract infections and blood poisoning) and for enterococci (which cause peritonitis, wound infections, urinary-tract infections and can be a particular problem for those on kidney dialysis).

On the specific issue of E. coli with ESBL resistance, we said that although the strains of bacteria found in animals and humans were generally different, there is strong scientific evidence to indicate that copies of ESBL resistance genes in farm animal strains of E. coli are transferring to those in humans and making them resistant.

In his second letter, David Burch questioned whether any of the human E. coli receiving the ESBL resistance genes from animal E. coli, to which we had referred, actually cause infections in humans. We all have E. coli bacteria in our intestines, and these don’t generally do us any harm. If some of them acquire resistance genes from farm-animal E. coli we ingest from meat or other foods, surely this doesn’t really matter unless they go on to cause infections?

This argument has held sway within the industry for many decades, but the reality is that some of the E. coli do go on to cause infections.

In our most recent letter in the Veterinary Record, we pointed out that several scientific studies have focused mainly on E. coli from human infections, and found that some of the E. coli have ESBL resistance genes on pieces of DNA which are highly similar or identical to the same genetic elements in the farm-animal E. coli. This is compelling evidence that the transfer of ESBL resistance genes from farm-animals to humans is a genuine medical concern, because when these bacteria are ESBL resistant, successful treatment is much more difficult and expensive.

E.coliWhen urinary-tract infections, which are commonly caused by E. coli, are not successfully treated with antibiotics, they have a greater chance of developing into blood-poisoning, a condition which can kill. As we showed in a report for the Soil Association in 2012, E. coli superbugs on farms and in food, E. coli blood poisoning infections in the UK have increased 4-fold over the last 20 years, partly due to increasing resistance caused by the overuse of antibiotics in both human and veterinary medicine.

The Chinese discovery

Another example of a resistance gene apparently transferring from farm-animal E. coli to human E. coli has been in the news recently. This time it concerns E. coli resistant to colistin, the last resort antibiotic used in human medicine for infections that don’t respond to treatment with other antibiotics. As the SFT reported in November, a new type of colistin resistance that spreads between bacteria, has been found in pigs, meat and human infections in China. The higher proportion of positive samples in the farm animals and retail meat than in human infections led the researchers to conclude it is likely colistin resistance originated in farm animals and subsequently spread to people.

The discovery of this new type of resistance caused laboratories worldwide to check their own archived collections of bacteria, and just before Christmas the Alliance to Save Our Antibiotics published a press release making public the fact that the resistant E. coli have been found in pigs and humans in the UK, by Defra and by Public Health England. This resulted in significant media coverage, such as this story by the BBC. In the past few weeks, this type of resistance has also been reported from Canada, Denmark, France, the Netherlands, Portugal and in several Asian and African countries. In the UK, colistin-resistant E. coli have actually been present since at least 2012, and in Canada they’ve even found cases going back to 2010, which predates the Chinese cases.

The colistin story doesn’t just provide further evidence of the spread of resistance from farm-animal bacteria to human pathogens, it also shows that this can happen for years without anyone noticing, unless robust surveillance systems are put in place. Most people would have assumed that economically advanced countries like Canada and European countries would be better placed to pick up on this development than China, but it was Chinese scientists who alerted the world to the problem. In fact, it’s only since 2014 that the EU has required any testing for colistin resistance to be carried out by Member States, which shows how lacking some of our systems have been.

The ease with which colistin resistance appears to be transferring between different strains of E. coli, and even into Salmonella, means that action needs to be taken urgently or the situation risks getting out of control. In Europe, over 500 times more colistin is currently used in farming than in human medicine. The European Medicines Agency admitted in November that there is an urgent need for it to review its earlier advice to the Commission that there was no evidence of colistin resistance being transferred from animals to humans and that the drug could therefore safely continue to be used for group treatments of pigs, poultry and cattle.

The example of colistin adds more weight to the growing realisation that we need an urgent and honest reconsideration of how all antibiotics are used in farming. The key reason for the concern about new types of resistance like ESBL and colistin is that so many other antibiotics are already failing and very few new ones are being developed.

We have reached the end of the line so quickly due to past misuse and overuse of all antibiotics. As such, the only sensible action is to restrict the use of all antibiotics to the treatment of illnesses that will not resolve naturally and not to use them preventatively, except in very exceptional circumstances. Let us hope governments around the world all listen to the recommendations of the O’Neill review.

Anyone with a particular interest in the issues highlighted in this article is welcome to contact SFT Policy Director Richard Young for further information.

The Sustainable Food Trust is a member of the Alliance to Save Our Antibiotics.

Photograph: Emily

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