Growing rates of antimicrobial resistance could leave us without effective drugs to treat serious infections – “the end of modern medicine as we know it”, according to the WHO’s Margaret Chan.
November 14-18 was World Antibiotic Awareness Week and Dr Siouxsie Wiles at Te Pūnaha Matatini planned an awareness campaign about antimicrobial resistance: InfectedNZ. It was postponed because of the Kaikoura earthquake and is running this week.
The Science Media Centre asked Dr Wiles and other experts to take part in a Q&A about antimicrobial resistance. Follow along with InfectedNZ blogs on Sciblogs.co.nz.
Q&A with Dr Siouxsie Wiles
Acting deputy director, Te Pūnaha Matatini
What is antimicrobial resistance and what is causing it?
“Antimicrobials are chemicals that kill or stop the growth of microbes. But as microbes is the generic term for a multitude of life forms which differ in their genetic make-up, life-styles and habitats, so antimicrobials can be divided into different categories depending on what they target. Some antimicrobials work against all microbes, but others are more specific. Antivirals only work against particular viruses, antifungals only work against particular fungi and antibiotics only work against particular bacteria.”
“Antimicrobial resistance is when microbes develop the ability to stop antimicrobials from affecting them. As most microbes replicate themselves and their genetic material fairly rapidly (some can divide in just a few minutes), and they can grow to large numbers (easily reaching population sizes in the billions if they have the right conditions), there are plenty of opportunities for resistant mutants to arise purely by chance. These mutants can then grow quite happily in the presence of the antimicrobial. This happens wherever microbes encounter antimicrobials – so in human and veterinary medicine, in agriculture, but also in sewage systems and out in the wider environment. More worryingly is when microbes gain the ability to share resistance between each other, on mobile bits of genetic material. Then they don’t even need to be in the presence of the antimicrobial agent – they just need to meet the right kind of resistant microbe!
“A major factor in the development of resistance is the misuse and overuse of antimicrobials. So being used when they aren’t needed, or not being used correctly. Another worry is the use of similar antimicrobials in human medicine and in agriculture. For example, a fungus commonly found in soil has become resistant to the antifungal pesticides used in gardening and agriculture. Because similar antifungals are used in human medicine, these resistant fungi are now able to cause almost untreatable infections in some vulnerable hospital patients. And these patients can become infected just by being in a bed next to open window that looks out onto a garden!”
Is antimicrobial resistance something we should be worried about?
“Yes. Experts predict that within the next decade we will run out of antimicrobial medicines to treat many common infections. Part of the reason we are in this position is that most of the pharmaceutical industry pulled out of antimicrobial research decades ago, so the medicine cupboard is basically empty. Similarly, the vast majority of government and charity funding around the world has gone on researching non-communicable diseases. Any new antimicrobial compound discovered today could take a decade of development and testing before it would be available for doctors to use. The situation is a catastrophe on a par with global warming.”
What are the most concerning examples of resistant strains of infectious diseases?
“The major resistant bacteria that are circulating around the world are extended-spectrum beta-lactamase (ESBL) expressing strains of Escherichia coli and Klebsiella pneumoniae, which are of particular concern in hospitals, and some strains of Mycobacterium tuberculosis which causes the lung disease TB. There are an increasing number of strains of these bacteria that are sensitive to just one or two antibiotics, and some strains that are pretty much untreatable. Another resistant organism of growing concern globally is Neisseria gonorrhoeae which causes gonorrhoea. While most men with gonorrhoea will have symptoms when they have the disease, half of women can be asymptomatic so won’t know they are infected. Importantly, untreated gonorrhoea can lead to infertility.”
How is New Zealand’s situation – are there particular areas of concern here?
“The extremely resistant strains of E. coli, K. pneumoniae and M. tuberculosis we see in New Zealand are mainly coming into New Zealand from countries like India, China and those in south-east Asia. This is going to be an area to watch, especially given the importance of countries like China for trade and tourism in New Zealand.”
“N. gonorrhoeae is another one for us to watch as highly resistant strains have been reported in Australia. In New Zealand, gonorrhoea is not a notifiable disease so the only data we have is based on the voluntary provision of the numbers of diagnosed cases from laboratories and sexual health and family planning clinics. In 2014, that number was 3,038, with 977 of these cases in young people under the age of 19. Less than half of sexually active young people report using condoms which would protect them from infection. If we end up with a completely untreatable strain of N. gonorrhoeae taking hold in New Zealand this could have a huge impact on our future fertility.”
“The last organism of concern here is Methicillin Resistant Staphylococcus aureus (also known as MRSA) which is very much a problem of our own making. Over the last few years there has been a huge increase in the number of skin and soft tissue infections caused by S. aureus in New Zealand. Alongside this, there has been a huge increase in prescriptions for a topical antibiotic called fusidic acid. As a consequence, one of the major clones of S. aureus now causing disease in New Zealand is an MRSA clone which is resistant to fusidic acid.”
What are some major misconceptions about antibiotics?
“There are a number of major misconceptions about antibiotics. Lots of people don’t know that bacteria and viruses are very different life-forms. This means that antivirals don’t work on bacteria, and antibiotics don’t work on viruses. In countries where antibiotics are available without prescription, many people confuse antibiotics with pain-killers, so will take antibiotics for things like a headache!”
“Another common misconception is that it is us that become resistant to antibiotics, rather than the microbes. Perhaps this is a misunderstanding between how antibiotics work (by killing the bacteria directly), versus what happens when we are vaccinated (our immune system is primed to recognise and fight off the invader).”
“But the biggest misconception is that people who don’t take antibiotics, or who take them very rarely, won’t be affected by antibiotic-resistant bacteria – that the antibiotics will still work for them. It doesn’t matter if you’ve never had a course of antibiotics, or if you’ve had several, it all depends on the bacteria you get infected with. Similarly, healthy people who have never had a course of antibiotics could still have antibiotic-resistant superbugs living happily up their noses or in their guts. They can easily spread from person to person, or can be picked up while traveling overseas.”
What does a future without antimicrobials look like?
“A future without antimicrobials will affect us all; rich and poor, young and old. In a world without antimicrobials, previously treatable infections will once again become deadly, or may require amputation to stop them in their tracks. Because antimicrobials are also used to prevent infection in vulnerable people, it will also become life-threateningly risky to do routine operations like caesarean sections and joint replacements, and treatments like chemotherapy for cancer.”
“Margaret Chan, Director-General of the World Health Organization, called antimicrobial resistance “…the end of modern medicine as we know it”. In a series of reports commissioned by the UK’s former Prime Minister David Cameron, economist Sir Jim O’Neill has estimated that without urgent action, antimicrobial resistance will kill 10 million people a year by 2050, more than will die from cancer. O’Neill has also put an economic cost on the issue, estimating that inaction will cost the world’s economy 100 trillion USD by 2050.”
What should we be doing to combat AMR?
“Combatting AMR requires a global effort to stop the overuse and misuse of antimicrobials in human and veterinary medicine, and in agriculture. It also requires governments, philanthropists, charities and industry to invest serious money into antimicrobial discovery and development and research into new ways to combat infectious diseases. Finally, we need quicker and better ways to diagnose infectious diseases so that patients can receive the right treatment as soon as possible.”
Are there any promising areas of research?
“Despite the lack of funding, there are plenty of researchers working in this area in New Zealand, like Dr Heather Hendrickson at Massey University who is hunting for phage, which are viruses that infect and kill bacteria, and Associate Professor David Ackerley at Victoria, who is searching for the genes that soil microbes use to make novel antibiotics.
“In my lab at the University of Auckland, we’re collaborating with my chemist colleague Associate Professor Brent Copp, and Landcare Research fungi expert Dr Bevan Weir to find new antibiotics from New Zealand fungi.”
Watch a video about the University of Auckland fungi project.
Q&A with Professor Pauline Norris
Professor of social pharmacy, University of Otago
How well does the general public understand antibiotics and when to use them? Does this affect their use?
“We have done research with a range of ethnic groups, occupational groups and the general population and found that misunderstandings about antibiotics are very common. Overseas research has also found this.
“Some common misconceptions that lead to over-use of antibiotics are:
- Many people think that antibiotics will cure illnesses like colds and flu. This is not true because these are caused by viruses, and antibiotics do not work on viruses (they only kill bacteria).
- Many minor bacterial infections will get better on their own and so taking antibiotics is unlikely to make a difference for these.
- Some people misunderstand what antibiotics are or what they do, so they may take them to treat all kinds of conditions that they are not helpful for.”
What role can or do doctors and pharmacists play in ensuring appropriate antibiotic use?
“Doctors can advise people about whether their illness is likely to be caused by bacteria and whether antibiotics would be useful. However, sometimes doctors feel that patients really want antibiotics so they prescribe them even when they might not be needed. So, if you would prefer not to take antibiotics it’s a good idea to tell your doctor this.
“Doctors and pharmacists can advise people how to take their antibiotics, for example, to finish the whole course and not stop when they feel better. This is important for making sure that all the bacteria are killed and reduce the development and spread of resistance.
“Pharmacists can also help with symptom management for colds and flu, because there is some evidence to suggest that symptoms like very sore throats lead to people requesting antibiotics.”
Is there any research to suggest ways to improve antibiotic use?
“Yes, there is lots of research exploring different ways to improve antibiotic use. What seems to work best is a combination of a variety of approaches together, such as patient education, feedback to prescribers and appropriate regulation. What works in one country may not work in another country: partly because the problems are different in different countries. For example, in many countries antibiotics are available without prescription and this leads to very high use.”
How does antibiotic understanding and use in New Zealand compare with other countries you’ve worked in?
“New Zealand has much better controls on availability of antibiotics than anywhere else I know of. As far as I know, it’s impossible to buy oral antibiotics in New Zealand without a prescription. In most countries, it’s illegal, but it happens. The quality of medicines is good in New Zealand, and this is also helpful. In some countries substandard medicines are common and this is likely to increase resistance because people are inadvertently taking only small doses.
“However, antibiotic use is high in New Zealand compared with other OECD countries. It has climbed dramatically between 2006 and 2014, and this is very worrying.
“I think it is common for people to have misconceptions about what antibiotics are and what they do in all countries.”
Q&A with Professor Kurt Krause
Director of the Webster Centre for Infectious Diseases, University of Otago
What is antimicrobial resistance and what are the most concerning examples?
“Antimicrobial resistance occurs when bacteria that are normally susceptible to the use of antibiotics develop the ability to resist the effect of these drugs. Physicians have been dealing with low levels of resistance to antibiotics for decades, almost since the beginning of antibiotic usage.
“However, in the past decade resistance has increased in frequency, severity and location. By increasing frequency I am referring the percentages of certain bacteria that are resistant. In some cases they are reaching 60-70% or even higher. By severity increasing, I am referring to the number of drugs to which a given bacteria is resistant. There are now bacterial resistant to essentially all antibiotics. By location increasing,I am actually referring to the increase in geographic area that is affected. For example, it used to be that MRSA – methicillin resistant staphylococcus aureus was a bacterium encountered in hospitals and ICUs – now it is found in the community.
“A most concerning example involves the group of organisms called the ESKAPE group that are resistant to almost all antibiotics. If resistance in this group spreads or increases, it will interfere with being able to effectively deliver medical care. Another particularly concerning group are the multi-drug resistant tuberculosis strains, which are very, very difficult to treat and they cause infections almost 1/2 million times each year.”
Are there any promising areas of research to help combat antimicrobial resistance? What should we be doing to combat AMR?
“We should be adopting a multi-point plan to help combat antimicrobial resistance:
1. Husband our current antibiotics by only taking them when needed. And when they are needed, by taking them fully and completely to avoid creating resistant strains
2. Carefully keeping track of current levels of resistant organisms and where they are located, and providing this information to clinicians to help them prescribe antibiotics appropriately. Antibiotic stewardship programs in our hospitals that assist in the management of infectious diseases need support. We need a well-trained and microbiologically savvy workforce.
3. Restrict antibiotic use in our animals to the treatment of infection, not for weight gain or growth.
4. Support research aimed at developing new antibiotics. New classes of antibiotics are urgently needed and scientific research must be undertaken now to discover the best new ways to combat infection. This kind of basic research will underpin the development of the next generations of antibiotics, which will lead to new treatments for infected patients.
5. Lastly we need to rethink our relationship with bacteria. Most bacteria are not ‘the enemy’. Most bacteria are not even pathogenic, and there are many more bacteria living in and on us, than our own cells! We need to learn more about what groups of bacteria promote health and what groups have potentially deleterious effects. Maintaining a healthy microbiome could turn out to be a vital new tool for global health.”
Q&A with ESR scientists
How do we monitor antibiotic use in New Zealand?
Antibiotic consumption in New Zealand is monitored by looking at the number of subsidised antibiotic prescriptions that are dispensed in the community. This data is collected by PHARMAC (the National Pharmaceutical Management Agency) and has been summarised by ESR in a recent report commissioned by Ministry of Health, Antibiotic Consumption in New Zealand, 2006-2014. The report provides information on antibiotic usage according to age, sex, ethnicity and region (District Health Board).
Antibiotic usage is expressed as the number of defined daily doses (DDDs) per 1000 persons per day. This allows usage of different classes of antibiotics (with different doses) to be compared consistently.
What trends have there been in antibiotic use?
Antibiotic Consumption in New Zealand, 2006-2014 noted some key trends in antibiotic consumption:
- A significant increase (49%) in antibiotic consumption over the period 2006–2014 (from 17.3 to 25.8 DDD per 1000 persons per day)
- The increase occurred across all age groups, in both sexes, amongst all ethnic groups and across all District Health Boards
- Age, ethnic and geographic differences in antibiotic consumption were marked, particularly for the penicillins (consumption of penicillins was generally highest in young children, in the upper North Island and in Pacific peoples)
- The top three most commonly prescribed antibiotics in 2014 were: doxycycline (25% of total consumption), and the penicillins, amoxicillin (25%) and amoxicillin-clavulanate (18%)
- Total antibiotic consumption in New Zealand was higher than 22 out of 29 European countries participating in antibiotic consumption surveillance in 2013.
How do we monitor antimicrobial resistance?
Most of the information we have on antimicrobial resistance in New Zealand comes from routine testing of bacteria undertaken in microbiology diagnostic laboratories. The bacteria are isolated from specimens taken from patients who have an infection, for example, a urinary tract infection. The patients may be in hospital or patients who present to their GP with an infection.
The results from this testing (which is called ‘antimicrobial susceptibility testing’) are used to calculate what proportion (usually percentage) of bacteria are resistant to an antibiotic. For example, from this testing we know that about 90% of Staphylococcus aureus, a bacterium that causes infections such as boils and abscesses, are resistant to penicillin, the first antibiotic to be discovered. On the other hand, this testing tells us that only about 8% of Staphylococcus aureus are resistant to flucloxacillin, the antibiotic now most commonly used to treat infections with this bacterium.
ESR collates the antimicrobial susceptibility testing results from diagnostic laboratories throughout New Zealand to estimate national rates of resistance and also to monitor changes in rates. In addition, ESR often collects the bacteria themselves from the diagnostic laboratories and undertakes more extensive antimicrobial susceptibility testing and specialist testing to determine the genetic basis of resistance.
Are there particular resistant bacteria that are of most concern in New Zealand?
Rates of antimicrobial resistance are relatively low in New Zealand compared with many other countries, including some of our near neighbours in Southeast Asia. However, resistance is generally increasing in New Zealand. Of particular concern is the high rate of resistance among Staphylococcus aureus to fusidic acid that has emerged following years of high use of topical preparations of this antibiotic. Also of concern are so-called ESBL-producing bacteria, especially when they cause infections in patients in the community who need to be treated with oral antibiotics. Given the range of antibiotics these bacteria are resistant to, there are very few oral treatment options available.
How do we detect emerging antimicrobial resistance?
New types of antimicrobial resistance, in particular multidrug-resistance or even pan-resistance (ie, resistance to all antibiotics), usually emerge in overseas countries where controls on the use of antibiotics are far less stringent than here in New Zealand. Therefore we essentially get ‘advance warning’ of the next threat on the horizon. This gives our laboratories, including our national reference laboratory here at ESR, time to ensure we have methods in place to detect multidrug resistance and new resistance mechanisms. In addition, hospitals ensure their infection control protocols are kept up-to-date to identify patients who are at risk of carrying or being infected with an emerging type of resistance. Such patients include those that have been in, and especially hospitalised in, countries where the resistance is common. Once identified, the patient would be placed in a single room “isolation” and screened for various resistant bacteria to prevent spread to other patients