Alexander Fleming’s serendipitous discovery of penicillin in 1928 was one of the most important medical breakthroughs of the 20th century. While antibiotics have since saved hundreds of millions of lives, the emergence of antibiotic resistant bacteria, or “superbugs” is now threatening to change the future of medicine.
The Conversation recently ran a nine-part series examining the rise of antibiotic-resistant superbugs and what we can do to avoid a return to the pre-antibiotic age.
Frank Bowden, Professor of Medicine at Australian National University and Senior Staff Specialist Infectious Diseases at ACT Health, opened the series with a reflection on the history of hand hygiene and how poor compliance among Australian doctors is putting patients at risk:
Infections, like taxes, are inevitable (to paraphrase Benjamin Franklin). Most are acquired in the community and the dangerous ones are, in the main, very difficult to prevent. But many infections are preventable and, regrettably, most of these occur as a consequence of hospitalisation.
It has been estimated that around 180,000 hospital-acquired infections occur in Australia each year and these infections result in almost two million additional days in hospital.
About ten years ago, health systems belatedly acknowledged that the means of reducing the transmission of infection in hospitals was right before our eyes: on our hands, to be precise.
John Iredell, NHMRC Practitioner Fellow and Head of the NHMRC Centre for Research Excellence in Critical Infection at University of Sydney, looked at the battle between naturally occurring and antibiotic-resistant bacteria in human ecology:
At the beginning of the 20th century, around one in three children in countries such as Australia and the United States died of infection before the age of five. But since Howard Florey first described the power of penicillin in 1947 and antibiotics became widely available, we have come to expect that life-threatening bacterial infection can be easily managed.
Early antibiotic therapy still means the difference between life and death for a previously healthy young person with a severe blood infection. However, we have long known that bacteria can quickly adapt to overcome the antibiotics that used to kill them. These antibiotic-resistant bacteria are often referred to as “superbugs”.
Trent Yarwood, Infectious Diseases Physician at Queensland Health and Associate Lecturer at University of Queensland, discussed the drivers of antibiotic resistance:
Antibiotic resistant bacteria are becoming a major problem. Calls to action on increasing rates of resistance have been made by the World Health Organization, the US Centers for Disease Control (CDC), and by the Australian Societies for Infectious Diseases (ASID) and the Australian Society for Antimicrobials (ASA).
And the media regularly features articles about superbugs and mega-superbugs. So why, if everyone is aware of the problem, are we still not winning the fight?
Antibiotic resistance is caused by excessive antibiotic use. If bacteria aren’t exposed to antibiotics, there’s no impetus for them to become resistant. But much modern medicine would be impossible without antibiotics (most surgery, for instance) so they are a necessary “evil”.
Darren Trott, Senior Lecturer of Veterinary Microbiology at University of Adelaide, outlined the hunt for superbugs in Australian livestock and companion animals:
Australia has some of the world’s most conservative restrictions on using antimicrobial drugs in livestock. Possibly as a consequence, we have some of the lowest rates in the world of antibiotic resistance in the bacteria (such as Salmonella and Campylobacter) that cause food poisoning.
Australian producers do not use broad-spectrum antibiotics such as fluroquinolones or gentamicin in livestock production. The antibiotic ceftiofur is governed by strict label requirements.
However, Australia is increasingly importing fresh food, including vegetables, from countries where these antimicrobial drugs are used indiscriminately in both animals and humans. Australia’s primary producers are under great pressure. They have to compete with cheap imported products that are often of inferior quality and may come from countries where the use of antibiotics in livestock is not so tightly regulated.
Bernd Becker, Senior Research Officer at University of Queensland and Matthew Cooper, Professor, Institute for Molecular Bioscience at University of Queensland, examined the strongest of the superbugs and the forgotten antibiotic that can fight them:
New Dehli metallo-beta-lactamase 1, or NDM-1 bacteria as they’re commonly known, are among the most dangerous superbugs to have emerged in recent years. They’re resistant to almost all the antibiotics we’ve discovered to date.
NDM-1 was first described in 2009 in a Swedish patient who’d been in New Dehli, India. It’s a gene that can be transferred between bacteria, which allows them to produce a very powerful enzyme that destroys what was previously our last line of defence – the carbapenem antibiotics (distant cousins of penicillin that were the last standard antibiotics still able to kill some of the earlier superbugs).
Now there’s only one antibiotic left that really works against this new generation of superbugs – a forgotten antibiotic called colistin.
Matthew Cooper, Professor, Institute for Molecular Bioscience at University of Queensland and David Shlaes, Anti-Infectives Consulting, looked at the issues blocking the antibiotic development pipeline:
Most experts considering the subject agree that the antibiotic development pipeline is not sufficient by a long shot. The days when there was always a new antibiotic just around the corner to treat the latest superbug are long gone.
Still, fixing the antibiotic pipeline is not rocket science. The main difficulty lies in finding molecules that enter the bacterial cell, stay there and inhibit growth of the bug without being toxic to us. What prevents us from overcoming this difficulty is that the number of people working on the problem has shrunk to historically low levels.
Marc Pellegrini, Researcher at the Walter and Eliza Hall Institute, pondered what we could learn from the past to avoid a future with no useful antibiotics:
History not only shows us our errors but also predicts our future. So, we don’t need to speculate about what a world full of superbugs and useless antibiotics would look like, we just need to recall the pre-antibiotic era (before the 1930s).
Our trajectory into the past is compounded by an ageing population that’s more susceptible to infections, overcrowded hospitals where infected and uninfected patients share facilities, a complacency toward basic hygiene principles and globalisation and its attendant increase in medical tourism that provides a free flight for any superbug seeking a new home.
Dyani Lewis, Sexual health researcher at University of Melbourne, examined the possibilities of poo transplants to restore balance in gut ecosystems:
Antibiotics joined our growing arsenal of weapons in the fight against disease over seventy years ago. Their target – the bacterial infections that putrefied our wounds, filled our lungs with pneumonia, and made our genitals less than appealing to our lovers. Bacteria were worthy opponents, and with antibiotics, the war against infection seemed ours to win.
But gradually, two facts have become abundantly evident. The first is that not all bacteria are foe. There are billions of bacteria – many of them essential to our health – that call us home. We’re each colonised by trillions of microbes forming communities that occupy every imaginable niche in our body.
Mark Butler, Senior Research Fellow at the Institute for Molecular Bioscience at University of Queensland and Matthew Cooper, Professor, Institute for Molecular Bioscience at University of Queensland, concluded the series with a look at what new and improved antibiotics are in the pipeline in the fight against superbugs:
Bacteria are one of the most successful colonisers of the planet. They can be found in almost all environments we know – from the deepest oceans to acid lakes, and inside and on our bodies. And the history of medicine is the struggle to defeat them.
One of the reasons for the success of bacteria is their rapid growth (some divide every 20 minutes) and ability to quickly mutate and exchange their genetic code (their DNA). These factors facilitate rapid evolution, which today has led to the emergence of drug resistance in bacteria. These bacteria eventually evolve into multi-drug resistant (MDR) bacteria, or “superbugs”, that are almost impossible to control. Some bacterial infections are so difficult to eradicate that amputation is the only option available to physicians.