eedwood House Farm is easy to miss. Only a small sign - the bright pink image of a pig - suspended from a fence post hints at anything of significance down the one-way track that leads off the main road. After a few hundred metres of bouncing over mud and gravel, it is the pungent smell that smacks you first. Then, the sound; the squealing, grunting and growls of 5,000 pigs crammed into this corner of rural Staffordshire.A hundred or so piglets are excitedly clambering over each other or snuffling around the muddy floor of the gated outdoor enclosure where they are waiting to be transported for slaughter. Inside the great barns, 500 sows lie side-by-side in pens while their offspring fight for space at their teats.The air hangs heavy with ammonia, so thick it stings the lungs.
This is the flagship operation of Midland Pig Producers, which runs nine farms across the country producing 80 tonnes of meat a week to supply leading supermarkets including Tesco, Marks and Spencer and Asda. It is big. But only a few miles away over the border into Derbyshire, something even bigger is planned.
A decision is expected shortly on Midland Pig’s so-called Foston Mega Farm, which will house 25,000 intensively reared indoor pigs, making it one of the largest in Europe. The proposal has attracted huge opposition, with more than 20,000 letters from across the world. Pig welfare is, of course, an emotive issue. But campaigners insist that something greater is at stake here - something that the Chief Medical Officer has referred to as one of the greatest threats of the 21st century, alongside terrorism and climate change, and which this spring, is expected to be placed on the national risk register. Such farms rely on the use of antibiotics for sick animals, but as we rush to produce industrial quantities of ever cheaper food, we have sleepwalked into a human health crisis.
National Risk Register
The government’s list of the greatest threats facing the country. Adding antibiotic resistance is being actively considered
This remains the most significant civil emergency risk. Three worldwide influenza pandemics occurred in the 20th century (1918, 1957 and 1968)
The east coast floods of 1953 were the worst peacetime disaster to hit the UK. As a result a national emergency was formally declared
Catastrophic Terrorist Attacks
Major terrorist attacks are an ongoing threat. The likelihood of terrorists obtaining effective biological or nuclear weapons remains 'not negligible'
Volcanic eruptions abroad
Volcanic eruptions abroad, such as the 2010 Icelandic ash cloud, can affect the UK. Effusive (gas-rich) eruptions are the most dangerous
A newly-assessed risk, wildfires - such as the Swinley Forest blaze in 2011, the largest in Berkshire’s history - spark massive devastation
70 per cent of the world’s bacteria have now developed a resistance to antibiotics. We have used - or are using - the drugs of last resort
As a result an invisible army of super-resistant bacteria has evolved, one that is increasingly claiming lives – currently more than 25,000 a year in Europe alone, around as many as die on the continent’s roads.
Many leading scientists and doctors and politicians are freely adopting the language of global catastrophe. Infections such as tuberculosis and septicaemia - the scourge of earlier centuries - are once again killing us at frightening rates. We have used, or are using, our so-called drugs of last resort. There is nothing left in the armoury and new drugs are not being developed. Welcome to the post-antibiotic age.
n 2012, at Needwood House Farm, a pneumonia outbreak swept through the herd. The piglets were taken off site and sows fed antibiotics with their food for six weeks. Those few that didn’t survive were incinerated. The outbreak – the first in eight years at the Farm - cost Midland Pig Producers £100,000.“Antibiotics are expensive,” says owner James Leavesley. “The last thing we want to do as a business is use them. We don’t unless we have to. It’s done because an animal – just like a human – can fall ill. If we need to stop using them on farms, can we stop using them in hospitals as well, please?”
“What we are proposing [at Foston] is going to be a cultural evolution. The whole point of the thing is to create an environment where we don’t need antibiotics.”
It is an admirable goal, but the reality is that modern British farms rely on antibiotics and on a vast scale. In 2012, some 409 tonnes of antibiotics were sold for animal use (a rise on the 346 tonnes sold the previous year), of which 85 per cent was for food-producing animals. The use of three classes of antibiotics classified by the World Health Organisation as “critically important in human medicine” has also increased. According to the latest Department for Environment Food and Rural Affairs (DEFRA) report, in 2012, 2.4 tonnes of fluroquinolone antibiotics were given to animals compared to 2.1 tonnes in 2011. Sales of the other “critically important” antibiotic classes - third and fourth generation cephalosporins (1.3 tonnes) and macrolides (40.9 tonnes) - also recorded small rises on the previous year.
“It’s getting worse, not better. It may be OK for five to 10 years but it’s not a sustainable model for the future. Otherwise we will lose our antibiotics.”Veterinary medicine accounts for around 30 per cent of antibiotics use in this country, and yet, we are one of the better regulated in the world. An EU-wide ban on the use of antibiotics as growth promoters in livestock has been in place since 2006. In Britain, only vets can prescribe antibiotics for animals, although critics say this raises an obvious conflict of interest when they also sell them. Worldwide, the majority of the 100,000-200,000 tonnes of antibiotics manufactured every year is freely used in the agricultural, horticultural and veterinary sectors to keep animals healthy on industrial-scale farms. “It’s getting worse, not better,” says Zac Goldsmith, the Conservative MP for Richmond and treasurer of the newly-formed All Party Parliamentary Group on Antibiotic Resistance. “When you concentrate a very large number of animals, particularly pigs, in very cramped conditions, you are going to create all kinds of local and environmental problems.
“History tells us you can’t keep animals in those conditions without almost daily use of antibiotics. It may be OK for five to 10 years but it’s not a sustainable model for the future. Otherwise we will lose our antibiotics. There are all kinds of implications about mega farms. I know that the total use [of antibiotics] per head per animal has gone up 18 per cent in the past 10 years.”
Goldsmith talks with a quiet urgency from the corner of a tearoom in the Houses of Parliament. For a long time, he says, he has been one of the few outspoken voices from the backbenches on antibiotic resistance. But not any longer. There is growing concern at the highest levels of Government over the seriousness of the issue. The June meeting of the Parliamentary and Scientific Committee to discuss antibiotics was standing room only in the Commons committee room. Looking down from the wall was a portrait of Lord Palmerston (prime minister 1855 to 1858 and 1859 to 1865). Once more we are engaged in gunboat diplomacy, the rhetoric of war.
The global habit that created a crisis
Six ways we have undermined a wonder drug. Click to read more
- AgricultureGlobally more than 70 per cent of antibiotics are used in animal agriculture including some of the most potent antibiotics available. In more than 100 countries antibiotics are routinely added to animal feed to promote growth. So-called mega farms, intensive meat and poultry farms where diseases can sweep through herds, are blamed in particular for overuse.
- AquacultureIntensive aquaculture (shrimp and fish farming) has led to growing problems with antibiotics routinely used to treat diseases. The industry supplies the world with 110 milllion metric tonnes of food fish per year. 75 per cent of the antibiotics fed to fish are excreted back into the water.
- VeterinaryIn Britain the veterinary sector has been criticised for irresponsible prescription of antibiotics, as vets can profit by selling the same drugs they prescribe. The government does not track the use of veterinary antibiotics in detail, with the main data available the total annual tonnage of antibiotics sold. In 2012, 409 tonnes of antibiotics were prescribed by vets in Britain.
- PrescriptionAntibiotics are commonly prescribed for respiratory infections, but most of these are caused by viruses not bacteria. Most patients are prescribed antibiotics without the doctor knowing the cause of the infection. GPs in England currently prescribe 35million courses of antibiotics a year.
- Patient pressureDoctors say they are put under huge pressure to prescribe antibiotics. Private doctors who see patients outside of hospital systems, such as those working in private offices, contribute disproportionately to the spread of antibiotic resistance. A 2012 survey in Australia, which has one of the highest rates of antibiotic use in the world, found 80 per cent of people who visited a doctor expected a prescription.
- Over the counter salesOver the counter antibiotics are available in many countries and are also easy to order over the internet. In some countries, hospitals make money from antibiotic sales. Up to a quarter of revenues in some Chinese hospitals derive from antibiotic sales. In March, the sale of antibiotics over the counter in India will be restricted for the first time.
- WaterUrban wastewater treatment plants are among the main sources of the release of antibiotics into the environment. Hospitals and drug manufacturing sites have the highest concentrations of antibiotics in their effluent, especially in developing countries where the majority of drugs are manufactured. Antibiotics have been detected in drinking water.
- SoilMany antibiotics are non bio-degradable and can persist in high concentrations in soil for a long time. An estimated 70 million tonnes of animal manure waste is spread on to agricultural land each year in Britain. Crops can take up substantial amounts of antibiotics by the roots. Antibiotics are also sprayed on to crops, such as high value fruit trees, to prevent bacterial diseases.
- WildlifeStudies are now finding antibiotic resistant bacteria among wildlife. Resistant genes have been detected in the bacteria of numerous animals ranging from gulls, crows and moths, to foxes and sharks. A study conducted in the Wirral found high levels of resistant bacteria in the faeces of forest rodents.
- TravelLast year the number of international tourist arrivals across the globe broke through the one billion barrier for the first time ever. We carry drug resistant pathogens everywhere we go. One recent study of Swedish world travellers found one in four young men were returning with antibiotic resistant bacteria present in their guts.
- MigrationMigrant workers have also led to unprecedented movement of antibiotic resistant organisms across international borders. Since 2004, more than one million migrants from Eastern Europe have arrived in Britain (around half have returned home) further spreading antibiotic resistant strains of tuberculosis. TB rates are higher than the UK in seven of the 12 accession countries.
- TradeAccording to the World Health Organisation, the growth of global trade allows resistant microorganisms to be spread rapidly to distant countries and continents through food. Global meat trade is a complex web of supply and demand. 60 per cent of the pork eaten in the UK is imported and around 40 per cent of fish produced in China is bought by EU countries.
- Patient movementMany healthcare patients now travel to foreign locations for medical treatment. Cosmetic, dental and even organ transplants are becoming more common as experienced surgeons and hospitals offer care at a fraction of Western prices. By 2015, it is predicted 3.2 million people will travel to India for cosmetic surgery or other operations.
- Hospital cleanlinessHospitals have become hotbeds for highly-resistant pathogens, like MRSA, ESBL, and CPE, increasing the risk that hospitalisation kills instead of cures. In many countries, the pharmaceutical industry is the principal source of prescribing information for doctors. Hospital patients generally have weaker immune systems and more wounds to infect.
- ProfitOnly four drug companies are left in the development of antibiotics. Antibiotics are not as profitable as other drugs taken for chronic conditions. Successful treatment with effective antibiotics takes only a few days compared to drugs for diseases like diabetes or blood pressure which people take for years.
- Difficult scienceBetween 1935 and 1968, 14 different classes of antibiotic were developed. In the 45 years since then, only five have been brought out. The pipeline for new replacement antibiotics is virtually dry. Mergers between pharmaceutical companies has reduced the number and diversity of teams seeking to discover new antibacterials.
- Complex regulationsLeading global drugmakers have said they need new incentives to stimulate research. Clinical trials are complex and cost a lot of money. The regulatory process is risk averse with high levels of bureaucracy and lack of clarity in the process.
Dame Sally and other experts say it is a practice we must stop now. “I care about my children and grandchildren, let alone my own old age,” she says. “If we don’t sort this out, not just as a nation, but globally, we risk going back to a time where people die young.
“We risk going into a post-antibiotic era, and that could start any time in the next 10 or 20 years, when modern medicine becomes impossible. Routine surgical procedures - hip replacements, caesarean sections, modern cancer treatments - all are based on using antibiotics to prevent or treat infections. Without them, people will die.
“Before antibiotics, 43 per cent of people died of infection in this country. At the moment it is seven per cent. I predict without proper conservation and new antibiotics, our death rate will steadily creep up. We risk returning to a situation like that. And the stupidity is, we don’t have to.”
o truly understand the extent of the problem, one must look beyond Britain’s borders. Compared to other countries, in particular the emerging powerhouses of India and China, we are well ahead in reducing use of antibiotics. But there is only so much we can do alone.This frustration was evident at the first evidence session of an ongoing parliamentary inquiry into antimicrobial resistance at Portcullis House which started in December. As Sharon Peacock, professor of clinical microbiology at the University of Cambridge told MPs: “Much of the resistance we see in this country is actually potentially imported from other places. We have to recognise that and understand what is happening in the bigger picture.”
Ours is a globalised world, and 70 per cent of the bacteria in it have now developed a resistance to antibiotics – including those drugs regarded as our last line of defence. Superbugs spawned in a Chinese hospital or a polluted Pakistani river cross continents quicker than we can discover them. One recent study of 100 Swedish travellers visiting countries outside of Northern Europe found one in four young men had antibiotic resistant bacteria present in their guts on their return.
How resistance breeds
Necessity negates political correctness. Only last month, Professor Ajit Lalvani, from the National Heart and Lung Institute, called for more screening tests to identify latent symptoms of TB that could be brought into the country by immigrants. For it is from distant shores where much of this bacteria comes from.
About 75 per cent of the cases nationwide occur among people born in countries where TB is more common, mostly South Asia (60 per cent of cases) and sub-Saharan Africa (22 per cent). Multi-drug resistant cases are also increasing in Eastern Europe. The complicated therapies required to treat the disease are more difficult to impose over language barriers and with vulnerable patients, resulting in unfinished courses of antibiotics; another major factor that increases resistance.
TB is by no means the only disease of concern. In November, the EU’s disease monitoring agency warned that Europe now faces a growing threat from bacteria that are resistant to the last-resort class of antibiotics known as carbapenems, with almost all European countries now having reported cases. The data from the European Centre for Diseases Prevention and Control showed that the proportion of bloodstream infections due to Klebsiella pneumoniae, a common cause of illness in hospital patients, that were resistant to carbapenems was now above five percent in 2012 in five countries - Greece, Cyprus, Italy, Romania and Slovakia. In 2009, only Greece and Cyprus exceeded that threshold.
Antibiotic consumption in Europe
Defined daily doses per 1,000 inhabitants per day
Data applies to prescriptions outside of hospitals *Country provided only total care data, which applies to community sector and hospital use
So many infections of gram-negative Acinetobacter, which causes a variety of diseases ranging from pneumonia to serious blood or wound infections, were recorded in troops in Iraq, that the disease was nicknamed “Iraqibacter”. Pathogens would also blow into soldiers’ wounds in the dust and dirt of Helmand Province in Afghanistan, causing a variety of diseases ranging from pneumonia to serious blood or wound infections. The number of cases fuelled claims that insurgents were lining IEDs with excrement or rotting animals.
And then, there are the medical tourists. Those who visit hospitals in Asia for cheap cosmetic surgery or other operations to avoid waiting lists are another main driver of the problem. In 2015, it is predicted 3.2 million people will travel to India for surgery. Here antibiotics are freely available for sale over the counter (at least until later this year when new laws come into place). “I think things have got progressively worse in Southern Asia, largely because of the medical tourism industry,” says Professor Tim Walsh, a microbiologist at Cardiff University. “If you look at the Calcutta Times, on the front page is a huge advertisement for cosmetic operations. People come from all over the world.”
“It’s almost like the perfect storm. It’s going to be very difficult for us to win this battle. In fact, I would say it’s impossible.”Walsh was part of the team that discovered NDM-1, an enzyme that confers resistance on a range of bacteria. In short, it makes already dangerous bacteria such as E.coli and cholera, far worse. The ND stands for New Delhi, where it was discovered in 2008. In the ensuing years it has claimed lives and spread panic far beyond the subcontinent. Walsh is currently assisting the UK government with estimates on the extent of antibiotic resistance by 2030-2050 and at the same time overseeing the world’s largest clinical trial in Pakistan and India looking at multi-drug infection in extreme drug resistant bacteria. The data, he says, “is quite frightening”.
“Bacteria are able to adapt, mutate, their DNA is very fluid. This is all happening in real time. We are up against a foe and it is a scenario combined with antibiotic industries around the world pumping out drugs and polluting environments, as well as overuse in our communities. Lots of countries have no idea at all about resistance rates.
“It’s almost like the perfect storm. Putting all that information together I would say it’s going to be very difficult for us to win this battle. In fact, I would say it’s impossible. Certainly it is going about it the way we are at the moment.”
One British man who, unlike the medical tourists, ended up in an Indian hospital against his will is freelance journalist Russell Cronin. In April 2011, during a meditation trip to Bihar, in northeastern India, the 49-year-old Londoner was electrocuted by a faulty shower at his hotel. He suffered horrific burns, which eventually resulted in him having his left hand amputated. After being treated at two Indian hospitals, the hotelier agreed to pay for a flight home to England, if Cronin wrote a note exonerating him from further liability. When he landed he was rushed from the plane to Bristol’s Frenchay Hospital where it was discovered, aside from the devastating injuries, that he had contracted five multi-drug resistant gram-negative bacteria carrying the NDM-1 enzyme, including a super immune strain of cholera.
“I was in a really bad way,” he says. “I didn’t know about the bugs until I came round and found myself in the isolation unit. They told me what it was but I had no idea what it all meant. I was still in a state of shock to discover that my hand had gone.”
Hospitals are increasingly being confronted with cases such as Mr Cronin, with antimicrobial resistance now costing the economy an estimated £10 billion a year. But those within the medical profession say students exhibit a staggering lack of knowledge about the issues we face. “One of the major problems we find is the lack of microbiology training that junior students have,” one consultant microbiologist says. “It is just two hours, in that time you can’t do anything. And it is now a very common practice in hospitals to use antibiotics of last resort. It’s very widespread and I have seen a lot of drug-resistant bacteria.”
In November, a Europe-wide study of final year medical students tested knowledge of antibiotic prescribing and resistance. Laura Piddock, professor of microbiology and deputy director at the institute of microbiology at the University of Birmingham and director of Antibiotic Action, describes the results as “lamentable”. “It’s not the fault of the students or the medical schools. The problem is the curriculum. What it means is we don’t get the time we would like to teach this area properly.”
ithout new drugs, there is no hope. Between 1935 and 1968, 14 different classes of antibiotic were developed. In the 45 years since then, only five have been brought out. No new classes have now been developed since 1987. The problem, is profit potential and profit depends on volume. Many pharmaceutical companies have pulled out of development altogether, focusing attention instead on drugs for chronic conditions, such as diabetes or blood pressure which patients have to take for years, rather than courses lasting just days or weeks. Professor Anthony Kessel, director of Public Health Strategy at Public Health England, says it is time to engage in a “moral debate” over the lack of new drugs, and admits rationing could now be on the horizon.“We may get to a situation where we have to think about rationing antibiotics. We are not there yet but if we really run out you can imagine that as a possibility. You can imagine a situation in the future where we have to develop a new antibiotic but not make it available straight away and keep it for emergencies. These are the type of solutions that we haven’t really talked about in great depth yet, but are possibilities.”
A history of resistance
- Antibiotic discovered
- Antibiotic resistance identified
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“A lot of companies have withdrawn from developing antibiotics. Only very few are doing it now”Payne says the difficulty is three-fold: poor profit potential; difficult science (the easier discoveries have already been made); and working around complex regulations, although he says the latter problem is now changing. According to a Chatham House report published last October, in 2004, only 1.6 per cent of drugs in development at the world’s 15 largest drug companies were antibiotics. GlaxoSmithKline is now just one of four major pharmaceutical companies left working on antibiotics.
“A lot of companies have withdrawn from this area,” Payne says. “If you go back 10 years just about every big pharmaceutical company you were aware of would have had a pretty large antibacterial discovery group. Only very few are doing that now.”
It may seem a bit rich for the global pharmaceutical industry to complain about profits when, this year, its value is expected to reach £550 billion. Yet it can cost, we are told, hundreds of millions of pounds to bring a new single drug to market. The profit imperative ensures that the drugs chosen for research are those most likely to provide high returns, while far more gets spent on marketing products than developing new ones. According to an analysis of drug company spending published in the British Medical Journal in 2012, for every £1 spent on basic research, £19 is spent on marketing.
The result is a yawning void, one that has prompted the Association of the British Pharmaceutical Industry, among others, to call for a comprehensive review of the research and development environment. The UK government’s new five-year strategy to tackle resistance does address this in part; some £4 million being allocated for a new research unit on antimicrobial resistance to be established by the National Institute for Health Research from this April. There are also plans to encourage greater public-private investment in discovery and development and promote more streamlined research and collaboration within the industry.
here is a growing political will to address a complacency that set in as far back as the 1970s and even now – without new drugs in the pipeline - better infection control has been proven to make an immediate impact on winning the fight against resistant bacteria. Health professionals point to plummeting MRSA death rates in Britain, which have fallen by around 80 per cent since 2008. Improving public awareness is also key. Around half of people in the UK still do not know that antibiotics are inappropriate to treat colds, flu and viruses, according to evidence given a few weeks ago to the Commons Science and Technology Committee.But it may yet still all prove to be too little, too late. Sir Alexander Fleming did warn us. During a speech in Stockholm in 1945 after accepting his Nobel Prize, Fleming sounded “one note of warning” over bacteria becoming resistant through inappropriate use of the drug. “The time may come when penicillin can be bought by anyone in the shops.’’ he said. The idea of his precious discovery being stockpiled by online pharmacies, used to fatten up our fish and livestock, dumped in rivers and sprayed over fields, would have baffled and horrified him in equal measure.
Today at St Mary’s – as in every other British hospital – that wonderful armoury, in which Fleming laid the first weapon, has been picked bare while the enemy has evolved. As Professor Jeremy Farrar, director of the Wellcome Trust, said in an interview last month, “We have been through a golden age and we have become complacent. We’re watching evolution happen. This will come up steadily over years and it has already started. It’s been happening for the last decade or more and will continue. It will creep up on us almost without noticing. This is getting to the tipping point where you and your families will start to see this.”
We are sleepwalking back into a time where something as simple as a grazed knee or a scratch acquired in the garden will start to claim lives. The golden age of medicine is behind us.
Author: Joe Shute
Editors: Liz Hunt, Joel Gunter, Cherrill Hicks
Designers: Mark Oliver, Scott Jones
Developer: Dan Palmer
Video: Julian Simmonds, Gregg Morgan
Title image: Alamy
Editors: Liz Hunt, Joel Gunter, Cherrill Hicks
Designers: Mark Oliver, Scott Jones
Developer: Dan Palmer
Video: Julian Simmonds, Gregg Morgan
Title image: Alamy