Apocalypse Now: The advance of drug-resistant bacteria threatens global health – what’s being done to protect us?
Imagine a world where simple surgeries carry the risk of death. Where common infectious diseases – which previously posed no threat – could kill you, and where giving birth becomes life-threatening.
Before the invention of antibiotics, this was the perilous existence of our ancestors. We could, however, be returning to those dark ages, as the overuse of antibiotics brings with it the very real worldwide scourge of antimicrobial resistance (AMR).
“The threat is very serious,” said microbiologist Dr Jessica Blair PhD, of the Institute of Microbiology and Infection at the University of Birmingham. “Multi–drug resistant infections currently kill 700,000 people annually and this figure is rising every year. If this rise continues at current rates then it is predicted that by 2050 there will be 10 million deaths every year due to multi-drug resistant infections.”
The lack of novel drugs in development to replace those we can no longer use, due to resistance, means that Chief Medical Officer for England Professor Dame Sally Davies’ warning of an “antibiotic apocalypse” was no exaggeration.
“The use of antimicrobials underpins modern medicine,” added Dr Blair. “Without action now many simple infections will once again become untreatable.”
AMR threatens the effective prevention and treatment of a continually expanding range of infections caused by microorganisms such as bacteria, parasites, viruses and fungi.
AMR occurs when these microorganisms alter after being exposed to antimicrobial drugs including antibiotics, antifungals, antivirals and antimalarials. Sometimes referred to as ‘superbugs’, microorganisms that develop AMR are rendering antimicrobial medicines ineffective, meaning that infections persist, increasing the risk of an infection – with nothing to fight it. New resistance mechanisms are now emerging all the time and spreading across the world, threatening global public health.
AMR is compromising the fight against diseases including tuberculosis (TB), HIV and malaria and – without antibiotics that work – the successful outcomes of minor and major surgery, and cancer chemotherapy will be seriously compromised.
Figures from the World Health Organisation (WHO) show that 480,000 people develop multi-drug resistant TB each year. According to Dame Sally’s foreword to a report on AMR, from Lord Jim O’Neill and the Institute and Faculty of Actuaries, 50,000 people are dying every year in Europe and the US from infections that antibiotics have simply lost the power to treat. She warned that the death toll could increase worldwide and that our ever-increasing life spans may end up falling.
“The projected figures are much more worrying. It is quite possible – and perhaps even likely – that the recent era of material mortality improvements will give way to many years of material mortality worsening,” Dame Sally warned.
One study concluded that 70% of bacteria around the world have already developed resistance to antibiotics, including colistin, which is described as the last resort of antibiotics, due to its side effects.
It’s not just the over–use and misuse of antibiotics by humans which has contributed to the crisis; the growth of factory farming is linked with the development of AMR bacteria. Indeed, two-thirds of antibiotic consumption in the EU occurs in animal farming.
The human – as well as the economic cost – of AMR is massive, and until new medicines are developed, it can only grow. But there are exciting new developments afoot, giving hope to a world currently under considerable threat.
Antibiotic Guardian campaign
The Antibiotic Guardian campaign from Public Health England is asking the public, students, educators, farmers, the veterinary and medical communities and professional organisations to choose ‘one simple pledge’ about how they will make better use of antibiotics to slow resistance. Go to antibioticguardian.com
In September 2016, 193 countries signed a landmark UN Declaration agreeing to combat AMR. Signed at the United Nations General Assembly in New York, the agreement followed a worldwide campaign led by Dame Sally and Health Secretary Jeremy Hunt to highlight the threat posed by resistance to antibiotics.
The nations duly committed to tackling drug-resistant infections as a priority, and agreed to develop surveillance and regulatory systems on the use and sales of antimicrobial medicines for humans and animals, encourage innovative ways to develop new antibiotics and improve rapid diagnostics. They will also carry out awareness-raising activities to educate healthcare professionals and the public on how to prevent drug resistant infections.
At the time, Dame Sally said: “We need governments, the pharmaceutical industry, health professionals and the agricultural sector to follow through on their commitments to save modern medicine.” The UN Secretary General is to report back on progress within two years.
Meanwhile, Dr Blair is spearheading a national campaign – Antibiotic Action. It is a public awareness initiative of the British Society for Antimicrobial Chemotherapy (BSAC) and works to inform everyone about drug resistance – including members of the public, scientists, HCPs and politicians.
“We need to make people aware of the issue of antibiotic resistance and try to help people understand the threat,” said Dr Blair. “The main messages are to urge everyone to use existing antibiotics wisely and promote the importance of infection prevention and control.” Go to antibioticaction.com
Discoveries in 2016
1. The European Commission (EC) granted marketing authorisation for AstraZeneca’s new combination antibiotic Zavicefta (ceftazidime-avibactam), developed for the treatment of patients with serious gram-negative bacterial infections, which require hospitalisation.
2. Scientists at Germany’s University of Tubingen discovered that people with the bug Staphylococcus lugdunensis (S. lugdunensis), present in their nostrils, were less likely to also have Staphylococcus aureus (S.auresus), including the superbug strain MRSA. Researchers identified the single gene that contained the instructions for building a new antibiotic which could treat superbug infections and named it lugdunin. Tests on mice showed that it could treat MRSA, as well as Enterococcus infections.
3. Life scientists at UCLA discovered that combinations of three different antibiotics from a group of 14 drugs can often overcome bacteria’s resistance to antibiotics, even if they are ineffective on their own or when combined with one other.
4. Symcel partnered with Colzyx to test 25 different new collagen VI derived anti-microbial peptides, analysing their capability to kill bacterial growth in different ways.
Wake up call
The ‘golden era’ of antibiotics research and development – when new medicines were being discovered – is toast. The old model, where pharma companies developed a new drug, then sold as much as possible of it, is no longer working, as old medicines lose their ability to fight infection. New products, therefore, must be used sparingly to avoid a repeat.
In his report, Lord O’Neill proposed a new way of repaying pharma companies for new antimicrobial medicines, through a ‘market entry reward’ payment of around $1.3bn (£890m) to the company that develops an effective new antibiotic for an ‘unmet need’.
Dr Jessica Blair is currently undertaking research to gain an understanding of the mechanisms of drug resistance in gram-negative bacteria. “By understanding the mechanisms we are better placed to target them with new drugs,” she said.
Dr Blair’s research involves efflux pumps – molecular pumps in the membrane of bacterial cells. “Efflux pumps are able to pump the antibiotic molecules straight back out of the cells allowing bacteria to survive the antibiotic treatment,” she explained. “Through this research we hope to be able to develop inhibitor molecules against these pumps that could be administered with existing antibiotics to restore sensitivity to these drugs.”
Dr Bjorn Herpers, clinical microbiologist at the Regional Public Health Laboratory in Haarlem in the Netherlands, said: “As all traditional antibiotics have eventually led to resistance, developing ‘new’ antibiotics of the traditional type isn’t the answer.”
The use of endolysins presents another new strategy. These are special enzymes that cleave the bacterial cell wall – a mechanism with no risk of generating resistance. “This resolves the doctor’s dilemma of not wanting to withhold a potential beneficial treatment to an individual patient, but having to be restrictive with antibiotics because of the risk of resistance induction,” added Dr Herpers.
Together with the Technical University of Zurich and the Dutch biotech company Micreos, he has successfully tested Staphefekt, the first endolysin available to the public for use against the bacteria Staphylococcus aureus, including the resistant type MRSA.
In further developments, Dame Sally Davies launched a new initiative at the London School of Hygiene and Tropical Medicine (LSHTM), in December 2016, to address the challenge of AMR. Giving the keynote speech at the launch of the School’s new Antimicrobial Resistance Centre, Dame Sally said: “We have a duty of solidarity to sort this, we cannot step back and watch it happen – we have to work out how to make a difference.”
The exciting research and development currently underway – along with action at local, national and international level – presents new hope that this potential global disaster can be averted.