Are you ready for a world without antibiotics?

[Guest guest]

Are you ready for a world without antibiotics?

Antibiotics are a bedrock of modern medicine. But in the very near future, we're

going to have to learn to live without them once again. And it's going to get

nasty. Boseley, Guardian, 12 August 2010

Just 65 years ago, Livermore's paternal grandmother died following an

operation to remove her appendix. It didn't go well, but it was not the surgery

that killed her. She succumbed to a series of infections that the pre-penicillin

world had no drugs to treat. Welcome to the future.

The era of antibiotics is coming to a close. In just a couple of generations,

what once appeared to be miracle medicines have been beaten into ineffectiveness

by the bacteria they were designed to knock out. Once, scientists hailed the end

of infectious diseases. Now, the post-antibiotic apocalypse is within sight.

Hyperbole? Unfortunately not. The highly serious journal Lancet Infectious

Diseases yesterday posed the question itself over a paper revealing the rapid

spread of multi-drug-resistant bacteria. " Is this the end of antibiotics? " it

asked.

Doctors and scientists have not been complacent, but the paper by Professor Tim

Walsh and colleagues takes the anxiety to a new level. Last September, Walsh

published details of a gene he had discovered, called NDM 1, which passes easily

between types of bacteria called enterobacteriaceae such as E. coli and

Klebsiella pneumoniae and makes them resistant to almost all of the powerful,

last-line group of antibiotics called carbapenems. Yesterday's paper revealed

that NDM 1 is widespread in India and has arrived here as a result of global

travel and medical tourism for, among other things, transplants, pregnancy care

and cosmetic surgery.

" In many ways, this is it, " Walsh tells me. " This is potentially the end. There

are no antibiotics in the pipeline that have activity against NDM 1-producing

enterobacteriaceae. We have a bleak window of maybe 10 years, where we are going

to have to use the antibiotics we have very wisely, but also grapple with the

reality that we have nothing to treat these infections with. "

And this is the optimistic view – based on the assumption that drug companies

can and will get moving on discovering new antibiotics to throw at the bacterial

enemy. Since the 1990s, when pharma found itself twisting and turning down blind

alleys, it has not shown a great deal of enthusiasm for difficult antibiotic

research. And besides, because, unlike with heart medicines, people take the

drugs for a week rather than life, and because resistance means the drugs become

useless after a while, there is just not much money in it.

Dr Livermore, whose grandmother died for lack of infection-killing drugs in

1945, is director of the antibiotic resistance monitoring and reference

laboratory of the Health Protection Agency. Last year, the HPA put out an alert

to medical professionals about NDM 1, urging them to report all suspect cases.

Livermore is far from sanguine about the future.

" A lot of modern medicine would become impossible if we lost our ability to

treat infections, " he says. He is talking about transplant surgery, for

instance, where patients' immune systems have to be suppressed to stop them

rejecting a new organ, leaving them prey to infections, and the use of

immuno-suppressant cancer drugs.

But it is not just an issue in advanced medicine. Antibiotics are vital to

abdominal surgery. " You safeguard the patient from bacteria leaking into the

body cavity, " he says. " If you lose the ability to treat these infections, far

more people would die of peritonitis. " Appendix operations would carry the same

risk as they did before Fleming discovered penicillin in 1928.

It may not be over yet, he says, but " we are certainly scraping the bottom of

the barrel to find antibiotics that are effective against some of the infections

caused by bacteria. "

Running out is not the only issue, he says. When somebody has a severe infection

– say blood poisoning – causing a high fever, a hospital clinician will dispatch

blood samples to the lab to find out exactly what he is dealing with. But that

takes time. " He will start you on antibiotics because that will kill infection

within 48 hours, " says Livermore. " So during 48 hours, you are being treated

blind. The more resistant your bacteria are, the less likely the antibiotic is

going to work. "

Studies have shown, he says, that the chances of dying from hospital pneumonia

or septicaemia (blood poisoning) are twice as high if the bacteria are

drug-resistant, rising in the case of pneumonia from 20-30% to 40-60%.

For a long time now, doctors have known they were in a race to stay a few steps

ahead of the rapidly growing resistance of bacterial infections to antibiotics.

Ten years ago, the so-called superbug MRSA caused front-page panic. Hospital

patients were picking up Staphylococcus aureus infections that were resistant to

the hitherto powerful antibiotic methicillin. All-out war, led by the

government's former chief medical officer Sir Liam son, against MRSA and

also C. diff (Clostridium difficile) has reduced the threat of what are known as

Gram-positive bacteria. Hospital hygiene has been massively stepped up and, in

response in part to public anxiety, pharmaceutical companies have put money into

finding new antibiotics for those infections.

But it's like putting a finger in a hole in the dam, only to find the water

surges out somewhere else. Bacteria are great survivors. The biggest threat now,

experts believe, is from multi-drug-resistant Gram-negative bacteria, such as

NDM 1-producing enterobacteriaceae and an enzyme called KPC which has spread in

the US (and in Israel and Greece) which also gives bacteria resistance to the

carbapenems, the most powerful group of antibiotics we (once) had.

" The emergence of antibiotic resistance is the most eloquent example of Darwin's

principle of evolution that there ever was, " says Livermore. " It is a war of

attrition. It is naive to think we can win. "

So the game now is to keep bacteria at bay. Hygiene is an obvious weapon. Better

cleaning, hand gels and stern warnings to staff and public alike have helped

reduce infection rates in hospitals. But Professor , director of

the centre for healthcare associated infections at the University of Nottingham,

warns that bugs don't stay in hospitals (indeed, the NDM 1- producing bacteria

appear to be widespread in the community in India, passed on through

contaminated water, in which people bathe, wash clothes and also defecate).

" The worry is once these organisms are out in the community, " says . " There

probably is some need for public education about infection and, for instance,

kitchen hygiene when you are cooking. People of my generation were taught a lot

about washing your hands before every meal. It was automatic that it was done. A

lot of that has gone. " There are some innovative ideas about, he says, on ways

of teaching children in school to wash their hands – in the hope that they will

then go home and pester their parents to do the same.

Beyond that, there is a real need to conserve those antibiotics we have. " To me,

it has many parallels with the problems of energy in economies around the

world, " he says. Carbon trading was dreamed up to try to conserve oil and reduce

its pollutant effects. There have now been a couple of interesting papers

suggesting a Pigouvian tax – which he defines as one levied on an agent causing

an environmental problem as an incentive to mitigate that problem – for

antibiotics.

Like oil, he points out, antibiotic usefulness is finite. And the cost of drug

resistance is not reflected in the price of the drug. " If you consider

antibiotic sensitivity as a resource like oil, you want to maintain that by

introducing a tax, " he says. It would be worldwide and the proceeds could fund

new drug development.

But should you tax life-saving drugs, especially in poor countries? " If you

don't do anything, there won't be any antibiotics anyway, " says starkly.

" At least it is a suggestion of something that could be done. "

If anybody had doubted it for a moment, Walsh's paper shows that neither the UK

nor any other country can pull up the drawbridge. " This report shows that the

battle to control the emergence of antibiotic-resistant superbugs through

appropriate use of antibiotics must be fought at an international level, " says

Kerr, consultant microbiologist at Harrogate district hospital. " It

illustrates the importance of considering health issues as a world issue – how

antibiotics are prescribed and controlled in one part of the world can very

rapidly have consequences elsewhere, " says , professor of

molecular genetics at the University of Birmingham.

" ly, pharmaceutical companies as well as governments and the European

Commission need to really get their act together, " says Walsh, who has been

urging co-ordinated efforts across the world to put in place good surveillance

systems to find out what resistance is developing and where, and then look for

interventions. He had Columbia, Mexico, Thailand and India all willingly on

board for one surveillance scheme, but the European Commission would not fund

it. " What we need is for somebody to give us something like €3m [£2.5m] a year.

It's not a lot of money. "

The fact is that many people have still got their heads in the sand. But soon we

will start seeing patients in NHS hospitals whose infections won't clear up. In

the battle for survival of the fittest between human beings and bacteria, just

now it looks as though the best we are going to get is a draw – if we are lucky.

After antibiotics: what happens when the drugs don't work

• Transplant surgery becomes virtually impossible. Organ recipients have to take

immune-suppressing drugs for life to stop rejection of a new heart or kidney.

Their immune systems cannot fight off life-threatening infections without

antibiotics.

• Removing a burst appendix becomes a dangerous operation once again. Patients

are routinely given antibiotics after surgery to prevent the wound becoming

infected by bacteria. If bacteria get into the bloodstream, they can cause

life-threatening septicaemia.

• Pneumonia becomes once more " the old man's friend " . Antibiotics have stopped

it being the mass-killer it once was, particularly among the old and frail, who

would lapse into unconsciousness and often slip away in their sleep. Other

diseases of old age, such as cancer, have taken over.

• Gonorrhea becomes hard to treat. Resistant strains are already on the rise.

Without treatment, the sexually transmitted disease causes pelvic inflammatory

disease, infertility and ectopic pregnancies.

• Tuberculosis becomes incurable – first we had TB, then multi-drug-resistant TB

(MDR-TB) and now there is XDR-TB (extremely drug resistant TB). TB requires very

long courses (six months or more) of antibiotics. The very human tendency to

stop taking or forget to take the drugs has contributed to the spread of

resistance.

http://www.guardian.co.uk/society/2010/aug/12/the-end-of-antibiotics-health-infe\

ctions