Antimicrobial Resistance

A report from Dr. Sally Campbell

“We need to join forces against resistant microbes” – with particular reference to current aquaculture practices

The further concern for us all, after microplastics, is the UK rising challenge of antimicrobial resistance, known by AMR, its three-letter abbreviation. It is estimated that over 700,000 people die each year across the world due to drug-resistant infections and it is predicted to increase to 10 million by 2050 if we take no action.

So, what are antimicrobials? Essentially a biologically active chemical or combination that kills or inhibits potential infections and include:
• Antivirals
• Antibacterials
• Antifungals
• Antiprotozoals
• Worms (antihelminthics)

The UK is 14th in a global list of 29 countries reporting antibiotic use in 2016. For every 1000 people 20 are on antibiotics at any one time, a high usage compared to Holland where the total is 10 in 1000. Misusing antibiotics is widespread. Lower mid-income countries use less, as you might expect in countries with less money to spend on health. The UK government aims to reduce inappropriate antibiotic prescribing in humans by 50% by 2020, so 10 per 1000 population will be on them at any one time, the glimmer of hope being that we can slow down resistance.

But more disturbing is that we use as much antibiotics in animals as in humans, 337 tonnes per year in the UK. Whilst that is the lowest tonnage since 1993, it is of major concern. Tetracyclines are in greatest use; they are broad-spectrum antibiotics whose general efficacy has been reduced with the onset of this antibiotic resistance. Despite this, they remain the treatment of choice for some specific indications. Tetracyclines are generally used in the treatment of infections of the urinary tract, respiratory tract, and the intestine and are also used in the treatment of chlamydia, especially in patients allergic to β-lactams and macrolides; however, their use for these indications is less popular than it once was due to widespread development of resistance in the causative organisms. “Last line” antibiotics are not meant to be used to treat or prophylactically administer to animals including farmed fish. But there is a large proportion of antibiotic residue in animal manure, since 83 million tonnes of UK livestock manure is produced per year. This manure is muck spread on fields; or directly discharged into the sea lochs of western Scotland from salmon aquaculture. It is estimated that in 1gm of manure there are 1X1011 bacteria so that means 1 x1029 bacteria spread on land from manure per year in the UK. The chances of AMR transmission to humans is problematic, as well as surface run-off from land into streams, rivers and into the marine environment. Aquaculture is also an immediate threat to promoting increased resistance of pathogenic organisms. The sea bed inshore sediment can in certain localities act as a sink for fish farm waste and there is a wide range or prevalence of resistance genes. Resistance is transferable and can move from one to another bacterium.

Reducing antibiotic use in food production:
Animal ingestion of antibiotics through direct administration accounts for 44 per cent of the UK’s total antibiotic consumption annually, having a direct knock-on effect on human antibiotic in-take. The farming of fish includes antibiotic use, some in feed and some in “emergency” control of infections. This is an additional source of pollution in inshore waters. There are clear implications for Policy and Environmental Management Practice. There are often indirect effects of pollution. Unintended consequences are of major concern. Most well-known effects are from pesticides. Many of us in older generations are familiar with the author and campaigner Rachel Carson and her book “Silent Spring”; the effect of DDT on the North American Eagle and other raptors forming paper thin eggshells, breaking in the nests, as they were incubated. The death of song birds due to DDT pesticides through eating dead insects in the 1950s and 1960s eventually drove drastic policy changes. Now it is bees and neonicotinoids, another pesticide with unintended consequences. These unintended consequences are said to result in a Tragedy of the Commons. But what is that? It is a term used to describe a situation in a shared-resource system where individual users act independently according to their own self-interest and behave contrary to the common good of all users by depleting or spoiling that resource through their collective action.

But this story of biologically disruptive chemicals is not just about antimicrobials. A recent example of unintended consequences was the White Rumped Vulture in India, which had a role in removing carcasses. The increased use of Diclofenac (sold to us humans under a number of trade names, the most common being Voltarol) as a nonsteroidal anti-inflammatory drug (NSAID) taken or applied to reduce inflammation and as an analgesic reducing pain in certain conditions. Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent – a 95% decline by 2003 and a 99.9% decline by 2008. The mechanism is presumed to be renal failure; however, the toxicity may be due to direct inhibition of uric acid secretion in vultures. Vultures ate the carcasses of livestock that had been administered veterinary diclofenac, and were poisoned by the accumulated chemical, as vultures do not have a particular enzyme to break down diclofenac. At a meeting of the National Wildlife Board in March 2005, the Government of India announced it intended to phase out the veterinary use of diclofenac. This is a salutary reminder:
“The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian Subcontinent that pose a potential threat to human health. In many places, populations of feral dogs have increased sharply from the disappearance of vultures as the main scavenger of wild and domestic ungulate carcasses. Associated with the rise in dog numbers is an increased risk of rabies and the deaths by rabies of almost 50,000 people”. The Government of India cites this as one of those major consequences of a vulture species extinction. A major shift in transfer of corpse pathogens from vultures to feral dogs and rats could lead to a disease pandemic causing millions of deaths in a crowded country like India; whereas vultures’ digestive systems safely destroy many species of such pathogens.

So, what about antibiotics in the environment? I was one of the first generation of children in the late 1940s to benefit from antibiotics for ear infections. I recall large white M&B tablets which my mother crushed in jam! Twice this resulted in a rapid return to health so avoiding surgery to drain the middle ear to avoid deafness. I am sure many of us had experiences like mine as a young child. But over the years since, there has been an increase in application for both human and increasingly animal health. With animals, especially as size of herds in intensive animal rearing or with increased biomass in salmon aquaculture farms, antibiotics are incorporated into feed often as a preventative measure or prophylactic use to lower the risk of disease occurring, even when the animal or fish is the not currently ill with a particular infection. Intensive rearing in mega-farms is proving to be possible only when antibiotics are administered on a day by day basis. This is having serious consequences in our environment, both on land, in fresh water and in the marine environment resulting potentially in very serious consequences for our ability to fight infections. The residues are excreted out into the environment, be it land or sea with little ability to degrade in conventional waste water treatment systems. So why does it affect us in our ability to fight infections?

Bacteria, viruses and other microbes have always mutated, and evolved, just as in the evolution of all living things. They survive the onslaught of medical intervention by mutating, changing their genetic defences, so our medical armoury no longer works against them, a sort of “survival of the fittest”.

What must increasingly happen in answer to this is the application of the Precautionary Principle, and a call to action. So, what is this Precautionary Principle? The principle is used as a strategy to cope with possible risks when extensive scientific knowledge on the matter is lacking. The need for much more investigative studies into the effects of AMR is paramount. Clearly risk is associated with abundance, not prevalence. If we cannot (yet) detect we cannot say there is no risk. We need to conduct much more comprehensive risk assessments, looking at the scale of pollution of estuaries and lochs is vital, to look for and assess antibiotic resistant genes (ARG). Clearly possible vectors of disease also include waste water, river catchment areas, and mobile carriers such as scavenger birds, gulls for instance; also, faecal material and waste antibiotic-treated food from salmon aquaculture in the west coast lochs in Scotland. Implications could be that using the marine environment for recreation, whether surfing, diving, kayaking, sailing and even paddling and collecting shells could pose a significant risk to humans now and in the future. The need to reduce antibiotics in aquaculture is especially important along the west coast of Scotland; there must be a compromise between dose and risk. For example, the economics of our tourist industry depends on a pristine marine environment so this could cause a reputational risk to the unique “Scottish “brand.

Clearly one way to reduce risk to human health, is to reduce fish biomass, whilst the present push from aquaculture companies and the Scottish Government is to massively increase biomass to increase markets and profitability. A local example is Marine Harvest, in North and South Carradale now wish to increase the maximum fish biomass on each farm by 50% from 2,500 tonnes to 3,750 tonnes. We already know that in just 2017, 108 kg oxytetracycline and almost 29kg tetracycline, two broad spectrum antibiotics active against a wide range of infections in fish and humans, were used in the Carradale salmon farms. The larger the total tonnage of biomass and stocking density in a salmon farm the greater the risk of infections, whether by viruses or bacteria or parasites such as sea lice, all of which encourage treatments potentially serious for the ecosystem and those that depend on it, be it microfauna, shellfish, dolphins or us. An aim should be to reduce our propensity to disinfect as much as possible whether justified or not. At least 3 Scottish Salmon Company farms in Loch Fyne have applied to increase biomass (tonnes) on their farms and this week two have been granted planning permission by Argyll and Bute Council. The other is still with SEPA. It has to stop!

Already it is known that in the sediment catchment of fish farms, both freshwater and marine, there is a wide prevalence of resistant genes in bacteria, which can spread from one to another bacterium. Salmon farmers will ask? Why do we need to act, where is the proof? We know enough to say there is a hazard, which poses unintended consequences for the ecosystem, and an unclassified, as yet, risk and threat. Are we as a society to move into a post antibiotic-era? Do we not need to safeguard intergenerational equity? We all need to understand that unintended consequences for us and the wider ecosystem are becoming urgent and critical. Like DDT before and diclophenac, both stories of unintended consequences, it is no good saying “where is the proof of danger?” Use the Precautionary Principle, call for action from the Scottish Government, SEPA, Marine Scotland and the multinational industry. Beware of the prevalent silo mentality…not proven, costs too much, employment, world markets, lobbying power of multinational salmon aquaculture etc etc, and proceed to demand 3 preliminary conditions
• Look at potential adverse effects
• Evaluate scientific data available
• Examine the extent of scientific uncertainty

Further, stakeholders, including communities, must be involved in forming a 25-year plan for water quality and the containment of microbial resistance. Community participation must include a push for evidence and reduce chemical contamination of our marine environment. Local Councillors must be educated in risk. We all also add to it, with pills and potions. This is a legacy issue, what do we leave for our grandchildren and our ecosystem? Will our great grandchildren need urgent surgery to drain middle ear infections or risk deafness, unlike my M&B tablets which killed the infection? We have failed as a society in that this slowly emerging crisis in antibiotic resistance has reached the environment without action. Our ecosystem health is at risk. It is up to us to demand remedial action now!

Dr Sally Campbell is a marine scientist and resident of the Isle of Arran
April 2018