There are only two major options to fight “superbugs” that laugh off available antibiotics: prevent those infections in the first place, or come up with new antibiotics.
The United States was making some progress on the first strategy before 2020, but the pandemic delivered at least a temporary setback. And efforts to encourage the second face significant hurdles: a Colorado senator’s bill to give drug companies incentives has stalled in Congress, and a different type of treatment being researched in Boulder is years away from reaching patients.
Bacteria, fungi and viruses are constantly evolving to get around the antibiotics used to kill them in people and livestock. While that might seem like an abstract concern, it has the potential to affect almost everyone: if there aren’t drugs that treat common infections, surgeries and immune-suppressing procedures like chemotherapy become much riskier.
While most bacteria are still susceptible to at least one antibiotic, resistant infections killed an estimated 35,000 people nationwide in 2019, according to the Centers for Disease Control and Prevention. That’s roughly the number of people who died of Parkinson’s disease that year.
The number may actually be higher, since the U.S. relies on several incomplete systems for counting the number of drug-resistant infections, and death certificates may simply note the person died of complications of another condition.
The Colorado Department of Public Health and Environment found 1,721 cases of drug-resistant bacteria or fungi between 2013 and 2019, but that’s almost certainly incomplete. Some infections are only recorded if they’re found in someone who’s hospitalized or living in a long-term care facility, while others are only tracked in the Denver area.
“Antibiotics can be life-saving, but it is important to use them appropriately,” Dr. Christopher Czaja, manager of the state health department’s health care-associated infections and antimicrobial resistance program, said in a statement. “The Colorado Department of Public Health and Environment has several programs to track antibiotic-resistant bacteria and stop the spread of those bacteria. We also work diligently with hospitals statewide to ensure appropriate antibiotic use.”
Drug-resistant infections were first identified as a problem in the 1970s, but there’s very little public awareness of them, said Anushree Chatterjee, who co-founded the Antimicrobial Regeneration Consortium at the University of Colorado Boulder. Member labs are testing new ideas to fight infections, with a pledge to donate the rights if they come up with something viable.
“It’s a silent pandemic,” she said.
“A complete market failure”
In 2019, the CDC identified five bacterial and fungal infections as “urgent”: drug-resistant gonorrhea; Candida auris, a fungus that resists multiple drugs; C. difficile, which causes severe diarrhea; and two types of bacteria that primarily spread in health care settings. In a report, then-Director Robert Redfield urged the public to stop referring to a “coming” post-antibiotic era.
“It’s already here,” he wrote. “You and I are living in a time when some miracle drugs no longer perform miracles and families are being ripped apart by a microscopic enemy. The time for action is now and we can be part of the solution.”
Dr. David Hyun, director of the Pew Charitable Trusts’ antibiotic resistance program, said that developing a new antibiotic can take more than 10 years and an average investment of about $1.3 billion.
Antibiotics don’t typically command high prices, though, and patients typically only need them for days or weeks. Major drugmakers have shifted their focus to more-lucrative drugs for chronic conditions, and several startups focused on antibiotics folded in recent years, Hyun said.
“The return on investment is just not there,” he said.
A bill sponsored by Sen. Michael Bennet, a Colorado Democrat, would attempt to make the economics work by committing the government to “subscriptions” for antibiotics. It has the unwieldy name Pioneering Antimicrobial Subscriptions to End Upsurging Resistance Act, abbreviated to PASTEUR. (Louis Pasteur was a French scientist who invented a process for sterilizing liquids and developed the first rabies vaccine.)
“We have a complete market failure in the United States and globally,” Bennet said at an event hosted by The Hill in May.
The bill would allow the government to guarantee between $750 million and $3 billion to companies that produce new FDA-approved treatments for the top threats. The payment size would depend on how novel the treatment is, and the money would be spread out over five to 10 years. Any purchases by federal agencies, like Medicare, would be deducted from the subscription amount so the government doesn’t pay twice. States and private health facilities would order and pay as they normally do.
Bennet and Sen. Todd Young, an Indiana Republican, introduced the bill in 2020 and again in 2021. It has Republican and Democratic supporters in the House of Representatives, but hasn’t made it to the Senate floor for a vote. Its chances are looking increasingly slim as the election nears, since Congress is typically less productive during campaign season.
A Bennet aide declined to discuss the bill on the record when contacted by The Denver Post.
Just providing financial incentives to pharmaceutical companies may not be enough to make a significant dent in the problem, though, Chatterjee said. If they develop antibiotics that are too close to existing ones, the bacteria will quickly become resistant, so it’s important to try new approaches, she said.
Chatterjee’s lab in Boulder is working on a nanoparticle to try to keep existing antibiotics working a little longer. Some bacteria essentially shut themselves down temporarily when certain antibiotics are present, meaning they don’t metabolize the drug and can reawaken once it’s out of the patient’s system. The nanoparticles keep the bacteria from shutting down, allowing the existing antibiotics to do their jobs, at least in petri dishes. So far, it’s proven safe in mice, but they have to test it in larger animals before considering human trials, she said.
Given the long time horizon, it’s vital to invest in ideas to combat resistance now, so they’ll be ready when they’re needed, Chatterjee said. If researchers hadn’t started looking into mRNA vaccine technology until COVID-19 hit, we still wouldn’t have the highly effective Pfizer and Moderna vaccines, she said.
“Things are going to keep getting worse,” she said. “I don’t think we should wait that long.”
COVID-19 set back prevention
The U.S. health care system was making some progress on reducing deaths from resistant bacteria before the pandemic, according to a 2019 report from the CDC. It estimated deaths had fallen about 18% since 2013, though that’s based on less-than-precise data.
Much of the work has been in hospitals, where measures like handwashing and regularly cleaning surfaces can prevent resistant bacteria from spreading between patients. Some hospitals were able to keep up their work on infection control and proper antibiotic prescribing after COVID-19 hit, but others essentially shut down those programs temporarily while they dealt with the crisis in front of them, Hyun said.
“The COVID pandemic response has really stretched the resources of some of these hospitals,” he said.
A study of about 5,000 COVID-19 patients hospitalized between February and July 2020 found about half received antibiotics, which aren’t effective against viruses. Only about a third of the patients who received antibiotics had confirmed or suspected bacterial pneumonia and 14% had a urinary tract infection, though it’s possible some others had different infections caused by bacteria. Bacteria may have settled into lungs already compromised by COVID-19 as a secondary infection, but the UTIs were most likely an unrelated problem.
It’s important to only prescribe antibiotics when patients need them, because bacteria will start evolving resistance as soon as they encounter a new drug, Hyun said. That’s going to require a change in how patients and doctors think, because prescribing antibiotics has typically been considered the “safe route,” though they can have significant side effects, he said. A recent study found children who received inappropriate antibiotics experienced more side effects than those who didn’t, ranging from rashes to infections with C. difficile, which can take over the intestines when beneficial bacteria are killed off.
The CDC has asked the public to be understanding if a doctor doesn’t think antibiotics are necessary, and if they are prescribed, to take the full course. Stopping antibiotics halfway through treatment gives bacteria with less-than-complete resistance a chance to keep evolving and multiplying.
Other measures ordinary people can take include preventing infections by getting all recommended vaccines, washing your hands and preparing food safely.
But one of the biggest things people can do is push their representatives for more action, Chatterjee said. Producing new antibiotics is going to take investment and streamlining of the process to bring them to market, she said.
“If there is a demand, the government will act,” she said. “When people stand up for something, change happens.”
