Hey readers,
Two years ago, the CDC made a disturbing prediction: that without radical change to antibiotic use practices, drug-resistant pathogens, which at that point were estimated to cause 700,000 deaths globally every year, could kill 10 million people per year by 2050.
A recent report published in The Lancet, however, found that the toll from antibiotic resistance is worsening even faster than expected.
Last month’s Global Research on Antimicrobial Resistance (GRAM) report estimates that in 2019, about 1.27 million people died directly due to antimicrobial resistance (AMR), which means cases where the patient wouldn’t have died had their infection been treatable with standard antibiotics.
Another 4.95 million deaths were associated with a drug-resistant infection, meaning that a patient died while having an identified antibiotic-resistant infection, but it wasn’t clearly the immediate cause of death.
The new numbers mean that AMR is now one of the leading causes of death worldwide, exceeding the toll of HIV/AIDS (860,000 deaths in 2019) and malaria (640,000 deaths). But while HIV research attracts close to $50 billion a year in funding, “global spending on addressing AMR is probably much lower than that,” as Ramanan Laxminarayan of the Center for Disease Dynamics, Economics, and Policy noted in a commentary published along with the Lancet study.
The overuse of antibiotics, whether in human patients or in livestock, results in bacteria adapting to the drugs, leading them to become less effective over time. If the pace of resistance isn’t halted — whether through more judicious use of the drugs or through the development of new classes of antibiotics — it will likely lead to soaring deaths from common infections and surgical complications, sending us back to a world where a minor cut could potentially once again be lethal.
We can avoid this fate, but it will require coordinating a global response before it’s too late.
Antibiotic resistance, explained
Antibiotics are drugs that kill or prevent reproduction of disease-causing bacteria, without directly harming the patient’s cells. The invention of the first antibiotics in the 1930s changed everything, offering nothing short of a miraculous cure for severe pneumonia or wound infections that otherwise might have left patients dead.
But due to their ability to reproduce rapidly — staphylococcus, for example, can double every two hours when colonizing the human nose — and to directly exchange fragments of genetic code, bacterial pathogens evolve far more rapidly than multicellular organisms like ourselves.
When a mutation arises that conveys resistance to an antibiotic, a large population of resistant pathogens can rapidly result, and the mutation can then be shared with other lineages of pathogen if they come into contact with each other.
Resistance can develop with remarkable speed. Methicillin-resistant staphylococcus aureus, or MRSA, was first documented in 1961, just one year after the antibiotic methicillin was introduced.
Every time a patient is treated with antibiotics while a given pathogen is present leads to a roll of the dice for a new resistance mutation to emerge. This isn’t just for human patients; the use of antibiotics for disease prevention and faster growth of livestock, which may account for an estimated 70 percent of antibiotics in the US alone, is also a major contributor to AMR.
How to resist antibiotic resistance
The Lancet study identifies three ways to slow the march of antibiotic resistance: more selective use of antibiotics, tighter infection control measures, and rapid investment in new treatments.
While the best practices for antibiotic usage in medicine are well established, they’re not always followed. Antibiotics are only effective against bacterial infections — meaning they’ll do nothing for a viral illness like influenza — and should be given only when medically necessary for an identified bacterial infection. However, a recent study estimates that 30 percent of the antibiotic prescriptions given in clinic visits are unnecessary, and this rises to around half for upper respiratory conditions (which are usually viral).
Treatment should always start with the most narrow-spectrum antibiotic, saving for later the “big guns” — broad-spectrum antibiotics, which are important to keep in reserve so they remain effective with the sickest patients, as well as newer drugs with less established resistance.
Once treatment is started, it’s important for patients to finish the full course; incomplete treatment can result in a surviving population of the disease pathogen, selected for resistance, which can then infect others and spread.
Cutting down on the use of antibiotics in farming is also essential. The low-dose, prolonged regimens given to increase the rate of growth in farm animals creates ideal conditions for pathogens to evolve resistant strains, at which point these pathogens can spread to affect humans.
Denmark has been a world leader here, drastically restricting non-therapeutic use of antibiotics in healthy animals solely for disease prevention and faster weight gain, but the US has yet to follow suit.
Preventing the transmission of infections within hospitals is also an essential measure to minimize the death toll from resistant bacteria; hospital-acquired infections are a major concern, with an estimated 650,000 cases annually in the US alone, and drug-resistant pathogens are much harder to treat, so maintaining isolation measures and the appropriate use of protective equipment is key.
These control measures can buy time for pharmaceutical research companies to invest in developing new generations of antibiotics to replace existing treatments as pathogens acquire resistance to them. But progress on new antibiotics has been slow.
Truly novel options — not simply tweaks on existing drugs — are what is most needed to stop drug-resistant pathogens, but the last entirely original class of antibiotics, lipopeptides, came out in the late 1980s.
New drugs required
The challenge is that successfully developing an effective and non-toxic new antibiotic is a long and complex process; since 2014, more than half of the drugs being tested were discontinued before reaching the approval stage. According to a 2017 estimate, a single successful antibiotic costs $1.5 billion to bring to market, whereas the expected annual revenue per drug is less than $50 million per year.
Since the most powerful antibiotics are held in reserve as much as possible and then prescribed only as short-term treatment for acute infections, they bring in much less revenue than drugs for chronic conditions such as high blood pressure or Type II diabetes.
Governments and other funders can respond by implementing financial incentives for companies, funding academic research, or making other significant changes to the current regulatory framework. And there is some good news on the antibiotic resistance front. The use of animal antibiotics decreased by 3 percent between 2019 and 2020, and the EU recently banned antibiotic administration to healthy animals. But much more is needed.
Antimicrobial resistance has been a hidden epidemic, less front-and-center than Covid-19, but the world cannot afford to wait to act until it reaches a crisis point.
—Miranda Dixon-Luinenburg
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