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These bacteria contain drug-resistant genes. It is the spread of bacteria among both animal and human populations that then creates superbugs.

By Rob Minto

The global superbug crisis is a complicated, long-term problem. The video below explains how it starts, spreads and its impact. But there are many other—sometimes surprising—aspects to this crisis.

There is one key way in which superbugs start. Whether it is in animals or humans, the initial point is where antibiotics kill off drug-susceptible bacteria, leaving drug-resistant bacteria to multiply.


These bacteria contain drug-resistant genes. It is the spread of bacteria among both animal and human populations that then creates superbugs.

These superbugs don’t respond to our available antibiotics. The end result is that many standard procedures—from caesarean sections to chemotherapy—may become too risky to undertake. It is projected that millions of people may die of what were once treatable infections.

1. Humans aren’t the biggest problem.

Although overuse of antibiotics in the human population is a problem for creating drug-resistant bacteria, humans aren’t the only creatures given antibiotics.

In fact, livestock is a much bigger problem. Around 70 percent of antibiotics in the U.S. are consumed by animals.

The consumption of antimicrobials by animals is projected to rise by 53 percent from 2013 to 2030, according to a paper published in Science: from an estimated 131,000 tonnes to 200,000 tonnes.

As the chart below shows, the main increase will be in China, unless measures are taken to prevent the overuse.


Antimicrobial consumption in food animal production.Science

2. We aren’t spending enough.

While throwing money at a problem is no guarantee of results, it is an indicator of how seriously governments and policymakers take it. Antimicrobial resistance (AMR) can be prevented by simple solutions such as better sanitation and sensible use of antibiotics, measures that cost comparatively little. However, AMR and drug-resistant genes require research too—into the development of new drugs, the spread of bacteria and other measures that could be costly.

Comparing worldwide estimated deaths from diabetes, cancer and AMR-related illnesses to spending by the U.S. National Institutes of Health research from 2010–2014, there is a direct trendline. Cancer research spending of $26.5bn dwarfs the $5bn and $1.7bn spent on diabetes and AMR respectively. But should AMR’s estimated deaths increase to 10 million, the current levels of spending look woefully inadequate.


Research spending and estimated deaths.AMR Review

3. Drug resistant infections are very expensive to treat.

Take tuberculosis (TB) as an example. Treating a drug-resistant strain of TB can cost nearly 30 times more than TB that responds to conventional medicine. The full treatment can also take up to two years and 14,000 pills, as well as six months of daily injections.


Cost per patient with TB.CDC, TB Alliance

4. Infectious diseases isn’t attracting new doctors.

According to AMR Review, the number of applicants for U.S. medical residencies and fellowships in infectious diseases (the area of medicine most relevant to combat superbugs) is below the number of places—at 0.8 applicants per place.

This is partly due to the fact that doctors in this area are paid less: according to the most recent Medscape compensation report 2017, in the U.S. doctors working in cardiovascular disease, radiology or plastic surgery are all paid around $400,000 per year; in comparison those working in infectious diseases get around $230,000.


Applicants per vacancy in different medical disciplines.AMR Review

5. Developing new antibiotics doesn’t pay off.

As the chart below shows, antibiotic research doesn’t start to pay off until year 23 of developing a new drug. After that point, the drug patent soon runs out and off-patent sales mean profits are much lower.

If the process is fruitless at any point before year 23, the company will make a loss.

Creating the right incentives to make new antibiotics is another crucial area for combating AMR.


Cumulative Profits from Antibiotic Research.AMR Review

6. The impact on the world will be unequal—and hit poorer regions harder.

Every area of the world will be affected by superbugs—but in terms of population impact, as the chart shows Asia and Africa will not only suffer more deaths, but more deaths per population.


AMR deaths per region and mortality rate.AMR Review, UN

Reposted with permission from our media associate The Bureau of Investigative Journalism.

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By Madlen Davies and Sam Loewenberg

Many of the world's leading drug manufacturers may be leaking antibiotics from their factories into the environment, according to a new report from a drug industry watchdog. This risks creating more superbugs.

By Madlen Davies and Sam Loewenberg

Many of the world’s leading drug manufacturers may be leaking antibiotics from their factories into the environment, according to a new report from a drug industry watchdog. This risks creating more superbugs.

The report surveyed household-name pharmaceutical giants like GSK, Novartis and Roche as well as generic companies which make non-branded products for the NHS and other health systems.


None of the 18 companies polled would reveal how much antibiotic discharge they release into the environment, according to the independent report from the not-for-profit body, the Access to Medicine Foundation. Only eight said they set limits for how much could be released in wastewater.

Only one disclosed the name of its suppliers—a move which is seen as important as it would make companies accountable for their environmental practices.

Commenting on the report, Dr. Mark Holmes, a veterinary scientist at the University of Cambridge, said, “Antibiotic resistance is complex but if we are to deal with this challenge every sector must do their bit. The pharmaceutical industry has been a key player in improving public health but a failure to address environmental impacts of antibiotic pollution could undo much of their good work.”

Changing Markets, an NGO which has campaigned on the issue of pharmaceutical waste, said, “Pharmaceutical companies have a clear responsibility to tackle pollution in their supply chains, not least because of the considerable human health impacts associated with untreated waste from pharma manufacturing, prime among the creation of drug-resistant bacteria. From our own research in India and China, where most of the world’s generic drugs are made, we know this is an ongoing problem and that very little progress is happening on the ground.

“As the report also highlights, there is a crying lack of transparency about pharmaceutical supply chains which means that we know practically nothing about where our drugs are made. This is a scandal and pharmaceutical companies will face increasing calls to do something about it.”

Antibiotic waste from pharmaceutical manufacturing leaking into the environment is a neglected driver of antimicrobial resistance—or AMR—according to a global report published in 2016 by ex-finance minister Lord Jim O’Neill. This is because residues of antibiotics in the environment expose bacteria to levels of the drugs that fuel the emergence of resistance. The “superbugs” that form as a result can spread all over the world. To tackle the problem, Lord O’Neill called for regulators to set minimum standards around the release of waste and for manufacturers to drive higher standards through their supply chains.

AMR has been described as one of the greatest health problems facing the world. Without effective antibiotics, infections become more difficult to treat and common medical procedures like joint replacements, C sections and chemotherapy care for cancer—which rely on the drugs to kill infection—could become too risky to carry out.

Last year the Bureau of Investigative Journalism reported on a study which revealed “excessively high” levels of antimicrobial drugs—as well as superbugs—in wastewater from a major drug production hub in the Indian city of Hyderabad. The quantities found were strong enough to treat patients, scientists said. This followed an earlier report of resistant bacteria in the wastewater of a factory there which supplies the NHS with antibiotics.

The Antimicrobial Resistant Benchmark 2018 report—released Wednesday at the World Economic Forum conference in DAVOS—evaluated how a cross-section of the pharmaceutical industry are responding to the threat of AMR.

It found none disclosed their actual discharge levels—information the authors said is “valuable and vital” as it could allow governments and researchers to understand the relationship between discharge and the development of superbugs.

Three generic drug companies—Cipla, Lupin and Sun Pharma—did not show any evidence of a strategy to minimize the impact of their antibiotic manufacturing on the environment, the report found, although Cipla promised to develop one this year.

Of particular concern were external companies that work for the main drug companies. Third-party companies manufacture and supply most drug firms with the key components of antibiotics, known as active pharmaceutical ingredients (APIs); and external waste treatment plants, which many drug companies use to process their discharge from antibiotic manufacturing. Some companies have on-site wastewater treatment.

Only eight companies set discharge limits for antibiotic waste, and for half the companies these limits only apply to their own sites, rather than their suppliers’ too. Only two companies—GSK and Novartis—require their external waste treatment plants to follow their limits. Sanofi and Roche, for example, do not monitor the discharge made by their external waste treatment plants, the report noted.

The Medicines Company was the only one willing to identify its third-party manufacturers, a move the report said would enable governments and researchers to assess the impact of individual manufacturers on antibiotic resistance. The report noted that pharmaceutical companies that sell antibiotics “may be able to exert considerable influence over the environmental risk management of their suppliers.”

The large pharmaceuticals polled were GSK, Johnson and Johnson, Merck & Co, Novartis, Pfizer, Roche, Sanofi and Shinogi. The generic companies were Aspen, Aurobindo, Cipla, Dr Reddy’s, Fresenius Kabi, Lupin, Macleods, Mylan, Sun Pharma and Teva.

Access to Medicine is an Amsterdam-based NGO that receives funding from the UK Government, the Bill & Melinda Gates Foundation and the Dutch Ministry of Foreign Affairs.

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Digitally-colorized scanning electron microscopic image of Enterococcus faecalis. Pete Wardell / CDC

A breakthrough in antibiotic resistance was reported last week. Scientists had re-engineered the drug vancomycin—used against extremely resistant infections including MRSA—to make it stronger and stop bugs becoming immune to it. Vancomycin has been prescribed for 60 years and is a highly effective antibiotic—yet in some countries bacteria are developing resistance.

Professor Dale Boger, of the Scripps Research Institute, California, had previously managed to make two tweaks to the drug in the lab to make it more potent. Last week, his team announced a final tweak, which when combined with the previous two would make it 1,000 times stronger than it was in its original form, and bacteria would no longer be able to resist it.

A breakthrough in antibiotic resistance was reported last week. Scientists had re-engineered the drug vancomycin—used against extremely resistant infections including MRSA—to make it stronger and stop bugs becoming immune to it. Vancomycin has been prescribed for 60 years and is a highly effective antibiotic—yet in some countries bacteria are developing resistance.


Professor Dale Boger, of the Scripps Research Institute, California, had previously managed to make two tweaks to the drug in the lab to make it more potent. Last week, his team announced a final tweak, which when combined with the previous two would make it 1,000 times stronger than it was in its original form, and bacteria would no longer be able to resist it.

In a press release announcing the breakthrough, Boger called vancomycin “magical” for its proven strength against infections, and said his team’s modifications had given the drug “superpowers.” The release described the breakthrough as “an advance that could eliminate the threat of antibiotic-resistant infections for years to come.”

Reporting on the story, British media outlets used similar language. A Daily Express headline announced the new vancomycin “could spell end of antibiotic resistant infections.” The Sun said scientists believed the breakthrough could “hold off the threat of antibiotic resistance.”

So does the development of this new drug really mark the end of superbugs? Professor Peter Wilson, a consultant microbiologist at University College London Hospital, is doubtful. The new vancomycin is only effective against one family of bacteria called “gram-positives,” he pointed out, which only account for some of the infections seen in hospitals. Most of these infections are not resistant to standard antibiotics and so the “super” vancomycin would have very little effect, he said.

What is antibiotic resistance and why is it so dangerous?

Both vancomycin-resistant enterococci (VRE) and VRSA feature on the World Health Organization’s list of bugs posing the greatest risk to mankind because there are so few drugs that can work against them. If scientists were able to make the new vancomycin into a drug it would be “fantastic” and doctors would welcome it, said Dr. Tim Jinks, head of drug resistant infections at the Wellcome Trust. Yet in practical terms the drug could only be used against a handful of infections.

Gram-positive infections include enterococci—bugs commonly found in the gut which can sometimes cause an infection, especially in patients already unwell with other illnesses. In the study, the beefed-up vancomycin was tested and found to be effective against normal enterococci and vancomycin-resistant forms of the bug. Other gram-positive infections treated with vancomycin include Staphylococcus aureus and its resistant types: methicillin resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA). VRSA is exceedingly rare in the UK.

Both Wilson and Jinks agreed that another family of bacteria—known as “gram-negatives”—pose a greater threat in the UK. Gram-negative infections—such as E.coli and Klebsiella—are a major cause of blood poisoning and are more likely to become resistant to antibiotics. E.coli is the most common cause of bloodstream infections in the UK. There were 38,000 bloodstream infections from E.coli in 2016 in England, compared to 1,099 in 2015/16 from MRSA. The new vancomycin would not work against a number of serious and life-threatening infections, both experts agreed.

It is also important to note the changes made to vancomycin were carried out in the lab. There were 30 steps involved to achieve the modified version. In order for the new drug to become available in hospitals and nursing homes, scientists would have to find a way to engineer—or synthesize it—with fewer steps and en masse.

Then, it would have to go through trials in order to become licensed and be tested for efficacy and safety on humans. That could take at least five years, said Jinks. The results are encouraging but there remains a desperate need for continued research and innovation to create new antibiotics, he said.

The Bureau asked Boger for comment but he declined to respond.

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