Not ‘if’ but ‘when’: Antibiotic resistance poses existential threat for modern medicine

In some ways, Melanie Lawrence is living a future that awaits us all.

She’s resistant to nearly every antibiotic and allergic or intolerant to the rest.

Now when she gets an infection, which she does every few months, she has to hope her immune system can fight it without much help from modern medicine.

Despite more than a century of antibiotic research and development, the world is quickly running out of these lifesaving drugs.

Antibiotics, either found in nature or developed intentionally, are designed to kill bacteria. But bacteria have been evolving for more than 3 billion years and have learned to change themselves to survive. The more we use them, the more they adapt.

In 2019, the last year data is available, more than 2.8 million Americans had antimicrobial-resistant infections and more than 35,000 died, according to the Centers for Disease Control and Prevention. Worldwide, deaths already top 5 million a year and are expected to grow into the tens of millions within a few decades.

“We are truly right now in the midst of this crisis,” Brenda Wilson, a Professor of Microbiology at the University of Illinois said in a recent American Society for Microbiology talk.

The U.S. was making solid progress against antibiotic resistance before the pandemic. Thanks to improved infection prevention and control and better stewardship, deaths from antimicrobial resistance declined by 18% overall and 30% in hospitals from 2012 to 2017.

But the pandemic pushed hospitals and other health care facilities near their breaking point in 2020, leading to an increase in antibiotic use, trouble following infection prevention and a significant increase in resistant infections in U.S. hospitals, the CDC found. Resistant hospital-onset infections and deaths both increased at least 15% that year, although data outside hospitals is lacking.

Overuse, both among people who would have recovered without the drugs and in livestock who get them to promote growth not treat illness, helps drive resistance.

Dealing with antibiotic-resistant infections already costs about $5 billion a year, said Brian Ho, who co-wrote a book with Wilson called “Revenge of the Microbes.”

And there’s a tremendous human cost, in addition to the financial one.

“A lot of what we do in medicine relies on our ability to handle bacterial infections that occur along the way,” said William Hanage, who co-directs the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health.

Minor injuries can become life-threatening without antibiotics.

Many surgeries wouldn’t be able to happen without knowing there were antibiotics to prevent any later infections.

Patients need antibiotics if they’re being treated with steroids or for cancer, rheumatoid arthritis, or other conditions that limit their immune response, as do people like Lawrence, who has cystic fibrosis, which makes her vulnerable to every passing bug.

“We want to be able to handle these things,” Hanage said.

Urging action

Lawrence, 43, traveled to Washington, D.C., earlier this month from her home in Fairhaven, Massachusetts, an hour south of Boston, to lobby the Senate for more funding and attention for antibacterial resistance.

She and others are encouraging Congress to pass a bill called the Pioneering Antimicrobial Subscriptions To End Up surging Resistance (or PASTEUR) Act, named for Louis Pasteur, the 19th-century Frenchman often considered the “father” of germ theory and modern microbiology. The bill was first introduced in 2020.

It would create new incentives for drug companies to discover and develop antibiotics.

Right now, there’s no financial incentive for a company to spend as long as a decade and upward of $1.5 billion developing an antibiotic that someone will use only for a week or two ‒ limiting the amount a company can charge ‒ and which might be obsolete in four or five years as bacteria become resistant.

“The market is broken because it’s focused on volume. Antibiotics should not be used in high volume,” said Dr. Helen Boucher, dean of the Tufts University School of Medicine, who also testified in favor of the PASTEUR Act. “PASTEUR reimburses for value, regardless of volume.”

Other places already have implemented similar financial models.

In the U.K., the government this month signed contracts with drugmakers Pfizer and Shionogi, guaranteeing them a fixed annual fee of up to $13 million for the next decade for two new antibiotics. Rather than paying the companies based on the volume of drugs sold, the new subscription model removes any incentive for overuse.

Also on the horizon are tests that help doctors quickly distinguish between an infection caused by a virus, which won’t benefit from an antibiotic, and one caused by bacteria, which might.

Earlier this month, the Food and Drug Administration cleared a test from Lumos Diagnostics of Australia that can rapidly identify a bacterial infection. And a July 13 study found The Karius Test, commonly used in hospitals, could distinguish among 700 types of microbes, including bacteria, viruses and fungi, in just one day.

Still, Lawrence thinks the world needs “more science, more attention to outsmarting these bacteria because we’re losing the race at this point.”

Careful use

Resistance develops when a small group of bacteria is different enough from the rest to survive an antibiotic onslaught. These remaining microbes then reproduce, taking over the infection, which is now unaffected by or resistant to the antibiotic.

“We should not be taking antibiotics unless it’s absolutely necessary,” said Dr. Adi Shah, an infectious disease specialist at the Mayo Clinic in Minnesota. “Giving an antibiotic for unclear or unnecessary reasons is like sending bacteria or a fungus to a gym to work out and form stronger defenses.”

To limit the overuse of antibiotics, doctors are now prescribing them less often and for shorter periods. Where someone 30 years ago might have been prescribed 10 days of antibiotics, and someone 15 years ago would have gotten a five-day prescription, they’re now getting the drug for two days.

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