Antibiotics: from life-saving discovery to the next pandemic?
Tipping points in the history of medicine and veterinary medicine
The COVID pandemic currently has our full attention, but there is a potential new health crisis looming on the horizon. Antibiotics are our most effective treatment for bacterial infections, especially when it comes to seriously ill patients who are already in a fragile state. However, these life-saving drugs have been affected by the threat of antibiotic resistance - also referred to as the 'hidden pandemic' - over the past few decades. We explored the history of antibiotics with three experts.
Antibiotics are an essential part of human and veterinary health care, but they also have a downside: the use of antibiotics has contributed to the proliferation of resistant bacteria. Antibiotic resistance is on the rise around the world, exposing people and animals to a greater risk of death from relatively harmless infections.
Jaap Wagenaar originally trained as a veterinarian and currently serves as Professor of Clinical Infectiology at Utrecht ľ¹Ï¸£ÀûÓ°ÊÓ. He is also working to address the problem of antibiotic resistance outside the Netherlands on behalf of the World Health Organisation (WHO), the United Nations Food and Agriculture Organisation (FAO), and the World Organisation for Animal Health (OIE).
is a medical microbiologist, Professor of Molecular Epidemiology of Infectious Diseases and Infectious Diseases and Epidemiology Coordinator at UMC Utrecht. He also serves on the Dutch government's Outbreak Management Team (OMT).
worked as a veterinary surgeon for some time after graduating in veterinary medicine. She is currently doing a PhD at Utrecht ľ¹Ï¸£ÀûÓ°ÊÓ, where she is working to improve the measurability of antibiotic consumption in poultry farms in Indonesia in order to reduce its use.
1870 – 1945: from the discovery of microbiology to penicillin
Since the discovery of micro-organisms in 1870, we have been aware that we share almost three quarters of our infectious diseases with animals and that the health of humans, animals and the environment is closely linked. Since then, we've been more aware of the need for personal hygiene when handling animals.
British physician and bacteriologist Alexander Fleming accidentally discovered penicillin in 1928: the substance - excreted by a fungus - accidentally found its way onto his culture plate. Penicillin proved to inhibit the growth of certain bacteria and eventually became the first viable antibiotic.
World War II accelerated the development of penicillin due to the need for large-scale treatments for bacterial infections, such as wound infections. After the war, penicillin use also rapidly increased in the Netherlands.
We share almost three quarters of our infectious diseases with animals
The 1960s: A focus on resistance
As researchers soon discovered, some bacteria can become resistant to antibiotics. This is partly due to the fact that these bacteria produce an enzyme that breaks down the antibiotic. The first warnings against resistance were issued in 1969 in the form of the Swann report, entitled 'Use of Antibiotics in Animal Husbandry and Veterinary Medicine'.
The report led to a ban on penicillin in animal feed, among other measures. Some countries also started requiring prescriptions for other antibiotics that were previously freely available. Professor of Clinical Infectiology Jaap Wagenaar: 'The Swann report set off alarm bells in the Netherlands. Despite considerable improvements in human medicine, veterinary medicine initially failed to recognise the urgency of the situation. Many developing countries also failed to address the issue.
These days, antibiotic resistance is mainly diagnosed using plates with 96 'wells' filled with sequences of different types of antibiotics. Growth in a well (as shown in columns 1 to 5) means that the bacterium is growing and is resistant to these antibiotic concentrations. The absence of growth (as shown in columns 6A to 6D) indicates that the bacteria are sensitive to the antibiotic concentration in those wells. These results are used as a basis for treatment recommendations and other applications.
So where do we currently stand?
Is antibiotic resistance really the next pandemic? Wagenaar isn't so sure: 'We seem to be on the right track: people are aware of the problem and we're seeing measures in various areas, even in developing countries. Still, it's definitely an ongoing cause for concern.'
'I don't think so', Marc Bonten adds. 'Pandemics are quick and severe. Antibiotic resistance does increase, but at a much slower pace - especially in humans. Even though resistance is growing and there are fewer and fewer antibiotics available, the majority of human infections are still treatable.'
Still, understanding the interactions between animals, humans and the environment remains a challenge, Bonten continues. The resistance genes of hospital patients can spread to humans, animals and the environment through the sewage system. 'We're currently trying to find out exactly how these bacteria and resistance genes spread. We're also studying plasmids - DNA fragments that can be transferred between bacteria - in order to gather useful information about resistance. We've brought these different areas of expertise together in the NCOH.'
The chickens we eat nowadays grow more slowly, and those extra days make a big difference
The future: alternatives to antibiotics
Bonten: 'Vaccines are the most important alternative, as far as I'm concerned. Immunotherapy, which uses targeted antibodies to sensitise bacteria to certain antibiotics, could also offer a solution. While that doesn't eliminate resistance, it does allow you to use more antibiotics.'
As Wagenaar sees it, humans and animals will need different solutions and alternatives. 'We need to prevent infections. That involves increasing resistance through vaccination, but a favourable climate and good nutrition are also important.
Factory farmed chickens are a good example: here in the Netherlands, we used to mainly eat chickens that matured from chicks to chickens in just six weeks. That rapid growth took its toll on their bodies. Wagenaar: 'The chickens we eat nowadays grow more slowly, and those extra days make a big difference.' Today's chickens are much stronger and hardly need any antibiotics. We might also be able to achieve similar improvements in the pig breeding and veal calf farming sectors. However, you always need the option of antibiotic treatment to ensure animal health and welfare.'
Bonten adds: 'The development of new antibiotics is currently on the back burner because it isn't interesting to pharmaceutical companies. The current drugs are cheap, safe and still effective enough. When things get really bad, powerful forces suddenly come together to accomplish things that were virtually impossible for 20 years.
In conversation with Indonesian poultry farmers
Micro-organisms don't respect national borders. We need to focus on the rest of the world as well as the Netherlands, which can be complicated by economic and cultural differences. While certain aspects of Dutch policy can be applied internationally, it's not a one size fits all situation as researcher Rianna Anwar Sani is well aware.
Antibiotic use in both humans and animals is extremely high in lower- and middle-income countries like Indonesia, according to Anwar Sani. 'These countries are becoming increasingly prosperous due to rapid population growth and urbanisation. The more prosperous people become, the more they will eat luxuries such as meat. As a result, the animal production chain in Indonesia - which consists of close to 90% chicken - has rapidly intensified. This chain is responsible for over half of all veterinary antibiotic use in Indonesia, a figure that is only expected to increase in future.'
Anwar Sani's research aims to determine which antibiotics are being used where, and in which quantities. She will be gathering this information by interviewing poultry farmers with between 5,000 and 20,000 broiler chicks. These farmers are representative of about 70% of the overall poultry production in Indonesia. They have relatively little knowledge of antibiotics and usually rely on the recommendations of commercial broiler and animal feed suppliers.
'We're going to train poultry farmers to improve their management and anti-infection measures. This should help them to abandon the excessive preventive use of antibiotics, which is currently at around 80%. While they do recognise signs of disease in their chickens, they tend to take action at the wrong moment: either pre-emptively or when it's already too late.
'We hope the outcomes of this research will actually improve the situation on the ground. We're actively partnering with local ministries in an effort to encourage policy reform. Involving farmers and other stakeholders in that process will be absolutely crucial.