Around the world, microbes are outsmarting drugs. If antibiotics against disease don’t work, bacteria could end up killing more people than COVID-19.
A girl suspected of suffering from drug-resistant typhoid receives medical treatment at a hospital in Hyderabad, Pakistan, 23 February 2018. (EPA-EFE/NADEEM KHAWER)
There is another epidemic raging alongside COVID-19. This epidemic claims 700,000 lives annually and costs global healthcare systems billions.
And we are still a long way from finding a way to halt its deadly progress.
The ungainly name of this second epidemic is antimicrobial resistance, or AMR. Simply put, it is the rise of bacteria impervious to antibiotics.
Across the globe, the microscopic pathogens that cause infections such as pneumonia and tuberculosis are evolving defences against our pharmacological weapons faster than we can develop new ones.
“Antimicrobial resistance has now reached epidemic proportions but remains out of sight for most of the general population,” wrote Dr. Ramanan Laxminarayan, Director of The Center for Disease Dynamics, Economics & Policy, in the preface to the CDDEP’s 2021 report on AMR.
Drug-resistant bacteria could kill many more than COVID-19.
When it arrived on the scene in the 1940s, penicillin seemed almost like a miracle cure to many doctors, who could previously do little to treat serious infections beyond hoping patient immune systems would kick in and kill the invaders.
Some miracles, though, have time limits.
Nearly 93 years after Sir Alexander Fleming discovered penicillin and 80 years since policeman Albert Alexander became the first patient to be injected with it, we may face a future in which broad-spectrum antibiotics are useless against most infections.
“Antibiotics probably, realistically, if we carry on with the trajectory which we are on, are only going to last for another 20-25 years,” Cambridge microbiology professor Dr. Stephen Baker, who spent 12 years studying AMR in Southeast Asia, said in an interview.
AMR will not rack up the rapid body count of the Spanish Flu or even COVID-19. But over the years to come, it will kill millions before their time, particularly the elderly and those with weakened immune systems.
“Overall, drug-resistant bacteria in the next 50 years are going to kill more people than COVID ever will,” Dr. Baker said. “It’s going to get worse and worse, given the kind of trajectories (we see) and how resistant these things get.”
Antibiotics in agriculture pose a threat.
In an interview, Dr. Laxminarayan cautioned against taking too bleak a view of the future and said estimates in a 2019 report by the Interagency Coordination Group on Antimicrobial Resistance of 10 million AMR-related deaths per year by 2050 likely overstated the case.
“It is not true that we will go back to a pre-antibiotic era, where millions of people died in the absence of antibiotics, because many other things were different at that time,” he said. “But that said, it is going to be a tragedy for many people, particularly the older age groups.”
In the past, poor infection control, hygiene, water quality and sanitation meant bacterial infections were more common. Deficient nutrition made for weaker immune systems. There have been improvements in much of the world since, but Dr. Laxminarayan believes much more can and should be done.
In a post-antibiotic era, diseases now easily cured will become debilitating or deadly again, while surgery, transplants, chemotherapy and other life-saving measures will carry a far greater risk if antimicrobials cannot be used to prevent and treat infections.
For bacteria, evolving resistance to antibiotics is a natural survival mechanism. The more antimicrobials are used, the more pressure microbes face to develop defences. Unfortunately, overuse of antibiotics is rampant throughout the world.
Livestock producers use them not just to prevent and treat infections in animals, but to boost growth — and hence profits. Dr. Laxminarayan said it is urgent that this practice should stop.
“We have to decide. Do we want to use antibiotics as an industrial input into agriculture, or do we want to use them to save lives? And I think the world has a choice to make,” he said.
‘The business model doesn’t work.’
Overuse is also far too common in human populations, particularly in lower- and middle-income countries, and global understanding of the dangers that poses is limited.
Slow progress on new treatments has helped resistant bacteria gain a foothold. The public and private sectors are not investing enough in research and development, and the pipeline of promising treatments may take up to 25 years to reach patients, Dr. Baker said.
Pharmaceutical firms are reluctant to stump up the kind of cash needed for breakthroughs in anti-infection drugs, which they cannot sell in sufficient quantities or at high enough prices to generate the kinds of returns they produce treating chronic conditions. Patients stop treatment once cured of infection, and there are limits to how much they will pay.
“The business model doesn’t work,” said Dr. Baker.
Some governments are investing in the handful of public-private partnerships focused on solving the AMR crisis, such as the Global Antibiotic Research and Development Partnership (GARDP) in Geneva. But far more targeted spending is needed.
The other factor contributing to the rise in resistance is societal inequality. AMR is more common in lower- and middle-income countries with poor water quality and sanitation, limited access to new antibiotics and vaccines, and weak healthcare infrastructure.
Progress has been slow.
In 2015, the World Health Assembly launched a Global Action Plan for defeating AMR. A year later, the United Nations General Assembly made a sweeping commitment to work on the problem together. But these pledges have yet to translate into widespread changes to public spending or policies.
“Overall progress has been slow,” said Dr. Laxminarayan, noting that global leadership, accountability, governance and the commitment of resources have all been lacking.
“It’s unfortunate, but five years after that UN resolution, with the exception of a few countries that were energized to do things on their own, progress has been largely missing in most parts of the world.”
Any solution to AMR must involve changes to how we approach human, animal and planetary health.
Infection control must improve across the world to curb the overuse and misuse of a dwindling stock of effective antimicrobials. Agriculture must phase out the use of antibiotics for animal growth.
In lower- and middle-income countries, spending must increase on water quality, sanitation, healthcare infrastructure and access to vaccines and affordable antibiotics. And substantial resources must be channelled into new therapies.
COVID-19’s lessons could help.
The battle against AMR may get help from an unlikely quarter, however.
While both Dr. Laxminarayan and Dr. Baker believe hospital-borne bacterial infections and antibiotic overuse may actually have increased during COVID-19, some in the scientific community hope the pandemic’s hard lessons about the economic and social consequences of incurable diseases may convince governments to take AMR more seriously.
COVID-19 has also made people more conscious of hygiene measures such as hand-washing. Perhaps most importantly, the massive spending that went into the hunt for a vaccine has prompted technological breakthroughs that may pave the way for new methods of infection prevention.
“COVID has pushed us into a new technological era on vaccine development,” Dr. Baker said. “I think that if you asked any biologist, they’d be very excited about the Pfizer and the Moderna platforms of developing RNA vaccines.”
We need to outsmart pathogens.
Vaccines are only one of a slate of promising potential alternative infection treatments. The others include monoclonal antibodies and other forms of immunotherapy that train the immune system to recognise certain pathogens, bacteriophages — bacteria-killing viruses — and antibiotics targeted at specific microbes.
But Dr. Baker believes the world is unlikely to see another broad-spectrum antimicrobial that offers the big bang solution penicillin did 80 years ago.
“Maybe, but I doubt it,” he said. “And if it does, drug resistance is inevitable. The moment we come up with a new compound that kills bacteria, the bacteria will learn how to become resistant to it.”
The best way to defeat pathogens that keep getting smarter about the weapons science levels against them is to get smarter about the pathogens themselves. Science must focus less on the quest for broad-spectrum antibiotics and more on developing what Dr. Baker terms “personalised microbiology.”
“There’s no magic bullet that’s going to come and kill everything,” Dr. Baker said. “What we need to do is go back to the drawing board or look at the ideas that we’ve got already, and then work out which ones are likely to be the technologies that we can begin to focus on over the next 25 years.”
Three questions to consider:
- What are the main reasons behind the rise in resistance to antibiotics?
- Why have pharmaceutical companies underinvested in the search for new drugs to treat infections?
- Why is it dangerous for farmers to use antibiotics to promote growth in livestock?
Sarah Edmonds has been a journalist for three decades. She spent 27 years with Reuters in seven countries on three continents, variously as a correspondent, news editor, bureau chief, regional managing editor and news operations manager.
Optimizing Genomic Testing for Antibiotic Resistance: Performance of the Unyvero HPN by Opgen.Inc was evaluated against standard of care (SoC) microbiological testing for detection of bacterial pathogens in lower respiratory tract specimens obtained from hospitalized COVID-19 patients with a clinical suspicion of secondary bacterial infection. Final results of this study have now been published in the European Journal of Clinical Microbiology & Infectious Diseases and found that the Unyvero HPN panel provides accurate detection of common agents of bacterial pneumonia with an overall high negative predictive value of 99.8% for pathogen detection. This could potentially allow for reduction in unnecessary antibiotic use and supporting antibiotic stewardship efforts.