SPOTLIGHT: Meet the York resistance fighters leading the war against superbugs

Penned by bestselling crime writer Val McDermid, Resistance opens at a music festival in the North-East of England. A mystery illness erupts, and then starts spreading. As the three-part drama unfolds, the disease becomes an uncontrollable epidemic.

It is a chilling account of Armageddon, says Jeremy Howe, Radio 4’s commissioning editor for drama. “Listener – you have been warned,” he says.

If you tune in you may find it terrifying. And you should. Because the epidemic it portrays is all-too plausible.

We thought we’d more-or-less conquered bacterial disease after Sir Alexander Fleming discovered penicillin in 1928. A whole range of antibiotics have been developed since. And infections that had been life-threatening suddenly became easy to treat.

The trouble is, we became complacent. We stopped developing new antibiotics. We began routinely using the antibiotics we have to treat comparatively minor infections, such as coughs and colds. And then we discovered that bacteria were evolving.

Over the last 10 to 15 years, more and more strains of bacteria have evolved which are resistant to antibiotics. MRSA is just one. Hospitals and health services across the UK and around the world are struggling to cope.

Eighteen months ago Dr Neil Todd, a consultant microbiologist at York Hospitals Trust, said it was no exaggeration to compare the threat of antibiotic resistance to that of global warming. “I’m extremely worried,” he said. “This is causing enormous problems for health services globally.”

Dr Neil Todd (left) with Prof Colin Garner and Ashley Burgess of Antibiotic Research Uk

The problem hasn’t gone away in the 18 months since. If anything, it is getting worse. Some forms of coliform bacteria that can cause cystitis and gut and kidney infections are becoming resistant to virtually all the antibiotics we have available, Dr Todd says. Cystitis was once easily cleared up by a course of antibiotics. But a patient with cytistis caused by a resistant bacterium now needs hospital treatment.

Quite common infections that cannot be treated can easily become more serious, leading to potentially fatal conditions. “We’re going to face very severe problems,” Dr Todd says.

Many in the medical profession now talk of a coming “post antibiotic age”, in which we will no longer be able to rely on antibiotics to treat infections.

What might that be like?

Modern medicine as we know it would no longer be possible, according to Professor Colin Garner, the former director of the Jack Birch cancer research unit in York, who has now turned his attention to the question of tackling antibiotic resistance.

The enemy: staphylococcus aureus

Simple operations – hip replacements or even tooth extractions – would become much more risky, because of the risk of infection. Transplants would become almost impossible. Cancer treatments, which suppress the body’s immune response, could lead to serious infections and death. Even childbirth would become more risky.

Even with advances in hygiene, a world in which we could no longer use antibiotics would be grim.

It already is. Professor Garner says that about 5,000 people die in the UK every year from antibiotic resistant infections. And if anything, that is an underestimate. Because of the way we record deaths, many are being attributed to conditions such as pneumonia or sepsis, without the presence of a resistant strain of bacteria being noted. So antibiotic resistance is probably already causing far more than 5,000 deaths a year in the UK.

The thing everyone is really frightened of, however, is a global pandemic – a rapid spread of disease caused by a virulent strain of resistant bacterium against which antibiotics don’t work. Just the kind of thing envisioned in Val McDermid’s radio drama, in fact.

Resistance is growing: Electron micrograph of E. Coli bacteria

If that ever happened for real, Prof Garner says, we could expect an appalling toll of deaths – as many as 250,000 people in the UK alone, according to some estimates.

So why aren’t we developing new classes of antibiotic? For the big pharmaceutical companies, the economics don’t stack up (see panel below). And while in the UK the government says it is making antibiotic resistance a priority, there has been no increase in research funding, Prof Garner says. There are just too many other priorities.

So there is, he says, a real danger that we are sleepwalking to disaster.

Where Big Pharma or national governments won’t take the lead, perhaps small charities can step in.

Professor Garner heads a national charity – Antibiotic Research UK, or ANTRUK for short – which is dedicated to finding ways of dealing with the threat of antibiotic resistance.

Instead of developing expensive new antibiotics, however, the charity is trying to do something much more cost-effective – find ways of making those we already have more effective.

There is evidence that by using antibiotics in combination with other, existing drugs, their potency may be revived, so that they can once again kill bacteria that had become resistant.

Lab workers studying bacterial resistance at the University of Warwick

Eighteen months ago, ANTRUK set out to test common antibiotics in combination with 1,600 other drugs already in everyday use.

It commissioned two private medical research companies – Evotec, which has labs in Manchester and Toulouse, and LGC Ltd, with labs in Cambridge – to test the antibiotic/ drug combinations against highly resistant strains of bacteria especially developed in the lab.

Drops of the drug combinations were added to cultures of bacteria under controlled conditions, and the cultures were observed after 24 and 48 hours to see if the bacteria had stopped growing.

The results have been encouraging. Thousands of drug combinations have so far been tested, and with testing not yet quite completed Prof Garner says 10 combinations have already been found which are effective in killing the bacteria.

In other words, ANTRUK has identified at least ten potentially effective new combination therapies, at a fraction of the cost of developing new medicines.

Resistant Enterobacteria cultured in a lab dish

So far, the testing has cost £125,000. The next stage will be to test the ten or more combination therapies in the lab on resistant bacteria taken from actual patients. The charity needs to raise £55,000 for that stage.

Stage three of the process will then involve testing the drugs on real patients, in a proper clinical trial. That will require a further £500,000. But at the end, there is a real chance that ANTRUK will have identified at least one, and possibly more, drug combinations that can be used against resistant bugs.

The beauty of the idea is that, because it uses already existing drugs, there is no need to get new drugs licensed.

“If we find something that’s effective in clinical trials, all we have to do is tell clinicians to use two drugs together,” Prof Garner says.

ANTRUK’s aim was to produce one such effective treatment by the early 2020s. It is well on track.

But even if it finds more, Prof Garner admits, this approach is only a stopgap.

Ultimately, if we’re to eliminate the threat of antibiotic resistance in the long term, we’re going to need to start developing entirely new antibiotics.

Which will mean Governments and big pharma throwing serious research money at the challenge.

If you’re sceptical about whether that would be money well spent – well, just listen to Resistance on your radio.

• Resistance, Radio 4, begins tomorrow at 2.15pm.

FROM RESEARCH TO EDUCATION AND SUPPORT

The charity headed by Prof Garner aimed initially only to try to develop new anti-bacterial therapies by using existing antibiotics in combination with other common drugs.
It has now broadened its aims, however, and plans to develop educational programmes as well as an online support network for patients who have suffered an antibiotic-resistant infection.
One of the reasons that antibiotic resistance is developing so quickly is that antibiotics are often prescribed – sometimes under pressure from a patient – for comparatively minor conditions such as coughs and colds.
This means that bacteria are exposed to antibiotics – and more quickly evolve to become resistant.
ANTRUK’s education programmes will aim to educate both members of the public and members of the health profession to use antibiotics only when really necessary.
The charity also aims to set up a support network via its Facebook page. 
“We find people are contacting us saying that they have got an infection, and asking us what we can do and if they can take part in a clinical trial,” Prof Garner says. “So we think we should be playing a role in helping them with information and support.”
ANTRUK is now looking to recruit volunteers – both health professionals who would be willing to give educational talks, and members of the public who would help with behind-the-scenes roles such as IT support, and with fundraising.
Several fundraising events are already lined up, including:

• Garden hog roast at Ebberston, near Pickering, with Charlie Heap and his birds of prey, Sunday July 9
• A day at Beverley Races, Yorkshire Day, August 1
• Cocktails and canapés at Bishopthorpe Palace, Thursday November 16, 6pm

For more details, visit antibioticresearch.org.uk/ or contact jenniferhildyard@talktalk.net

WHY DRUG FIRMS AREN'T DEVELOPING NEW ANTIBIOTICS

There is a reason why big pharmaceuticals companies haven’t been taking the lead in developing new antibiotics: money.
The economics were spelled out by Dr Patrick Vallance, president of Pharmaceuticals Research and Development at GlaxoSmithKline (GSK) in a talk at the University of York.
Speaking at the opening of the university’s new biology teaching and learning building, Dr Vallance said it would cost hundreds of millions of pounds to develop a new class of antibiotic. But the problem was that, once it was ready, we wouldn’t be able to use it.
That’s because once a new antibiotic is used, it will be exposed to bacteria – and resistant strains will begin to develop. 
So any new class of antibiotic should ideally be “put on a shelf” and kept until it was really needed – when there was a major epidemic caused by resistant bacteria, Dr Vallance said. 
“But that’s not a brilliant economic model, to spend £1 billion and then put it on a shelf until the patent has expired and anybody can use it,” he said.