Just 65 years ago Dr David Livermore’s paternal grandmother died after an operation to remove her appendix. It didn’t go well, but it wasn’t 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 few 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, in August posed the question itself, revealing the rapid spread of multidrug-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.
The discovery of NDM 1
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 the powerful, last-line group of antibiotics called carbapenems.
A recent paper revealed that NDM 1 is widespread in India and arrived there 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 said. “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 heart medicines, people take the drugs for a week rather than for life and because resistance means the drugs become useless after a while, there just isn’t much money in it.
Livermore, whose grandmother died for lack of infection-killing drugs in 1945, is far from sanguine about the future. “A lot of modern medicine would become impossible if we lost our ability to treat infection,” 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 isn’t just an issue in advanced medicine. Antibiotics are vital to abdominal surgery. “You safeguard the patient from bacteria leaking into the body cavity,” he said. “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.
Finding effective antibiotics
It may not be over yet, he said, but “we are certainly scraping the bottom of the barrel to find antibiotics that are effective against some of the infections caused by bacteria.”
Studies show 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% to 40%. 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 in the United Kingdom. Hospital patients were picking up Staphylococcus aureus infections that were resistant to the hitherto powerful antibiotic methicillin.
All-out war, led by the UK government’s former chief medical officer Sir Liam Donaldson, 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 improved 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 that has spread in the United States (and in Israel and Greece) that also gives bacteria resistance to the carbapenems, the most powerful group of antibiotics we (once) had.
“It is a war of attrition. It is naive to think we can win,” said Livermore.
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 Richard James, the director of the centre for healthcare associated infections at the University of Nottingham in central England, warned 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,” said James. “There probably is some need for public education about infection and, for instance, kitchen hygiene.”
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 said. Carbon trading was dreamed up to try to conserve oil and reduce its pollutant effects.
There have now been a few papers suggesting a Pigouvian tax — which he defined as one levied on an agent causing an environmental problem as an incentive to mitigate that problem — for antibiotics.
Like oil, he said, antibiotic usefulness is finite. And the cost of drug resistance is not reflected in the price of the drug.
Such a tax 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,” said James.
In the battle for survival of the fittest between humans and bacteria, it looks as though the best we are going to get is a draw — if we are lucky. —