Antibiotic apocalypse: doctors sound alarm over drug resistance

The frightening prospect that even routine operations will be impossible to perform has been raised by experts alarmed by the rise of drug-resistant genes

Scientists attending a recent session of the American Society for Microbiology reported they had uncovered a highly disturbing trend. They revealed that bacteria containing a gene known as mcr-1- which bestows resistance to the antibiotic colistin- had spread round the world at an alarming rate since its original discovery 18 months earlier. In one area of China, it was found that 25% of hospital patients now carried the gene.

Colistin is known as the” antibiotic of last resort “. In many parts of the world physicians have turned to its use because patients were no longer responding to any other antimicrobial agent. Now resistance to its employ is spreading across the globe.

In the words of England’s chief medical officer, Sally Davies:” The world is facing an antibiotic apocalypse .” Unless action is taken to halt the practices that have allowed antimicrobial resistance to spread and routes are found to develop new types of antibiotics, we could return to the days when routine operations, simple wounds or straightforward infections could pose real threats to life, she warns.

That scaring prospect is likely to be the main points of a major international conference to be held in Berlin this week. Organised by the UK government, the Wellcome Trust, the UN and several other national governments, the session will be attended by scientists, health officers, pharmaceutical chiefs and politicians. Its undertaking is to try to accelerate measures to halt the spread of drug resistance, which now threatens to remove many of the major weapons currently deployed by doctors in their war against disease.

The arithmetic is stark and disturbing, as the conference organisers make clear. At present about 700,000 people a year die from drug-resistant infections. However, this global figure is growing relentlessly and could reach 10 million a year by 2050.

The danger, say scientists, is one of the greatest that humanity has faced in recent times. In a drug-resistant world, many aspects of modern medication would just become impossible. An instance is provided by graft surgery. During operations, patients’ immune systems have to be inhibited to stop them rejecting a new organ, leaving them prey to infections. So doctors employ immunosuppressant cancer drugs. In future, however, these may no longer be effective.

Or take the example of more standard operations, such as abdominal surgery or the removal of a patient’s appendix. Without antibiotics protecting children during these procedures, people will die of peritonitis or other infections. The world will face the same dangers as it did before Alexander Fleming discovered penicillin in 1928.

” Routine surgery, joint replacings, caesarean section, and chemotherapy also depend on antibiotics, and will also be at risk ,” says Jonathan Pearce, head of infections and immunity at the UK Medical Research Council.” Common infections could kill again .”

As to the causes of this growing threat, scientists point to the widespread misuse and overuse of antibiotics and other drugs and to the failure of pharmaceutical companies to investigate and develop new sources of general medicines for the future. Western doctors are over-prescribing antibiotics to patients who expect to be given a drug for whatever complaint they have. In many countries, both land and fish farmers use antibiotics as growth promoters and haphazardly pour them on to their livestock. In the latter case the end outcome is antibiotics leaching into creeks and rivers with alarming results, particularly in Asia.

” In the Ganges during pilgrimage season, there are levels of antibiotics in the river that we try to achieve in the bloodstream of patients ,” says Davies.” That is very, very disturbing .”

The creation of these soups of antibiotic-laden water and banks of drug-soaked clays is ideal for the development of “superbugs”. Rare strains that are resistant to antibiotics start to thrive in farm animals that are raised in these artificial environments and emerge as highly potent infectious agents that then spread across the planet with startling speed. Instances of this involves tuberculosis, which was once easily treated but which, in its modern multi-drug-resistant form, known as MDR-TB , now claims the lives of 190,000 people a year.

Another even more uncovering instance are offered by colistin.” Colistin was developed in the 50 s ,” says Matthew Avison, reader in molecular biology at Bristol University.” However, its toxic side-effects built it unpopular with physicians. So it was taken up by vets and used in animals. But as resistance- in humen- to other antibiotics has spread, doctors have returned to colistin on the grounds that it was better than nothing .”

Levels
Levels of antibiotics in major rivers such as the Ganges are cause for alarm, says England’s chief medical officer, Sally Davies. Photograph: Alamy

But the antibiotic’s widespread employ as a growth promoter for poultry and swine in Asia had- by this time- encouraged the evolution of resistant stress and these have now spread to humen.” Colistin was a drug we disposed and devoted to the veterinarians and now, all of a sudden, we expect that we can take it back again ,” said Avison.” However, the genie is already out of the bottle .”

The position is summed up by Lance Price, an antibiotic researcher at George Washington University in Washington DC.” Superbugs are gaining strength because we continue to expend these precious medications through overuse in human medication and as cheap production tools in animal agriculture .”

Bans on the agricultural use of antibiotics like colistin are being imposed in Asia but have come far too late to be effective, a number of problems acknowledged by Lord Jim O’Neill, whose report to the UK government on antimicrobial resistance was published last year.” When we were putting our report together, colistin resistance was considered to be a problem that would not affect us for some time. Now we find it has already spread all over the place .”

The report that was overseen by O’Neill- who will be speaking at this week’s seminar in Berlin- put forward a number of proposals to stop antibiotic resistance from overwhelming health services. In particular, it argued that narcotic companies should now foot the bill for the drafting of new antibiotics and that patients should not be allowed to get them without a test to ensure they are needed.

” I find it incredible that doctors must still prescribe antibiotics based only on their immediate assessment of a patient’s symptoms, just like they used to when antibiotics first entered common use in the 1950 s ,” O’Neill said in the report, adding that the development of rapid diagnostic tests on patients- which would establish whether an antibiotic was necessary and, if so, which kind- must now be an urgent priority.

The proposal- to be debated at the conference the coming week- is popular, although Professor Alastair Hay of Bristol University advised caution.” It is a very good notion, but we should note that a new type of diagnostic exam like this will also add period and work for our already overburdened health service ,” he points out.

Then there is the issue of travel, one of the biggest problems we face over the spread of antimicrobial resistance, according to Davies, who has spearheaded Britain’s part in the battle to fight its spread around the world.

” One Swedish analyse followed a group of young backpackers who went off on holiday to different parts of the world. None had resistant bacteria in their intestines when they left. When they returned a quarter of them had picked up resistant bugs. That shows the permeating nature of the problem we face ,” she said.

Tourism, personal hygiene, farming, medical practice- all are affected by the issue of antibiotic resistance, and it will be the task of the conference to highlight the most effective and speedy solutions to tackle the crisis.

” In the end, the problem posed to the planet by antimicrobial resistance is not that difficult ,” says O’Neill.” All that is required is to get people to behave differently. How you achieve that is not so clear, of course .”

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From Viagra to Valium, the drugs that were discovered by accident

From Alexander Fleming onwards, the lives of millions have been transformed and saved by treatments that scientists were not even looking for

When scientists in New Zealand discovered that a meningitis vaccine fortuitously protects against gonorrhoea, they were benefiting from an unpredictable force responsible for some of history most striking medical breakthroughs: serendipity.

So many things have been discovered by chance. The German writer, scientist and all-round polymath Johann Wolfgang Goethe, a discoverer himself, wrote: Discovery requires luck, invention, intellect none can do without the other.

Viagra

In pharmaceutical giant Pfizers laboratories in Kent, a failed treatment for angina accidentally became a billion-dollar erectile dysfunction blockbuster, and the worlds most well known blue pill.

During early clinical trials of sildenafil , now better known by its trade name Viagra, male volunteers taking the pills consistently reported unprovoked, long-lasting erectings. After further investigation, it turned out that Viagra, designed to relax blood vessels around the heart to improve blood flow, was having the same effect on arteries within the penis. Since its commercial release in 1998, it has been used to improve the sexuality lives of millions of men worldwide.

Incidentally, the 2007 Ig Nobel Prize, awarded annually for that years most useless research, was awarded to three Argentinian scientists who discovered that Viagra helped hamsters regain faster from jet-lag.

Penicillin

Returning to work after a month-long Scottish vacation in 1928, pathologist Alexander Fleming made a discovery in a discarded culture dish, which he had unintentionally left open to the elements on a window sill in his laboratory at St Marys Hospital in London.

In Flemings absence, the dish, growing the dangerous bacteria staphylococcus aureus, had become contaminated with an air-borne mould a type of fungus. Fleming “ve noticed that”, near the blue-green strands of fungus, growth of the bacteria had been stopped in its tracks.

Fleming had unknowingly stumbled across the first antibiotic, which he called penicillin.

For his accidental discovery, he shared the Nobel prize for medicine in 1945 with Florey and Chain, Oxford chemists who perfected the process of penicillin mass production in time to treat infected battlefield injuries sustained in the second world war.

When I woke up just after dawn on 28 September, 1928, I surely didnt plan to revolutionise all medicine by discovering the worlds first antibiotic, or bacteria murderer, Fleming subsequently remembered. But I suppose that was exactly what I did.

Heart pacemaker

New York engineer Wilson Greatbatch fabricated the worlds first implantable heart pacemaker but he didnt mean to.

While trying to build a device to record heartbeats in 1956, he accidentally installed the incorrect type of resistor into his prototype which promptly began to emit regular electrical pulses.

Realising these heartbeats were recapitulating the electrical activity of a normal heartbeat, Greatbatch instantly assured the potential of his device. After two years of refinements, his design for a pacemaker that could be implanted into the heart was patented in 1960 and soon went into production. Life-saving descendants of this first device now improve the lives of over half a million patients with slow heartbeats every year.

Stomach ulcers

In the 1980 s, two Australian doctors were ridiculed for suggesting that belly ulcers were caused not by business lunches and stress, but by infection with a common bacteria. Barry Marshall, a gastroenterologist and his pathologist colleague in Perth, Robin Warren , noticed that stomach biopsies taken from their ulcer patients all contained the same spiral-shaped bacteria, called helicobacter pylori.

To demonstrate their hunch, Marshall intentionally downed a pint of foaming helicobacter broth that hed grown in his lab after isolating it from the stomach of one of his patients. Within a week, he had rampant stomach inflammation when it was completely reversed by taking antibiotics.

Their discovery has also entailed the virtual eradication of a type of belly cancer caused by helicobacter infection.

For their work( and presumably Marshalls courage ), Marshall and Warren were awarded the 2005 Nobel prize for medicine.

Antidepressants

Several classes of antidepressants owe their discovery to chance, from iproniazid, which was initially used to treat tuberculosis in the 1950 s, to the tricyclics of the 1960 s, which stemmed from an experimental therapy for schizophrenia and the most recent breakthrough involving the use of ketamine.

Valium

The entry-level benzodiazapine was developed in the 1950 s by a Polish immigrant in the US, Leo Sternbach, from disposed chemical compounds he had synthesised 20 years earlier in Poland when he was working on experimentations to create new dyes.

The dyes were a failing. The benzodiazapines speedily became the more popular prescription drugs in the US.

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