As interest lost in new antibiotics, infections only growing stronger
Forget COVID-19, monkeypox and other viruses for the moment and consider another threat troubling infectious disease specialists: common urinary tract infections, or UTIs, that lead to emergency room visits and even hospitalizations because of the failure of oral antibiotics.
There’s no Operation Warp Speed charging to rescue us from the germs that cause these infections, which expanded their range during the first year of the pandemic, according to a new Centers for Disease Control and Prevention report. In the past year, the FDA declined to approve two promising oral drugs — sulopenem and tebipenem — to treat drug-resistant UTIs, saying it needed more evidence they work as well as current drugs.
In the meantime, some UTI patients “have to get admitted and get an IV treatment for a bladder infection that typically would be treated with oral antibiotics,” said Dr. Sarah Doernberg, an infectious disease specialist at the University of California-San Francisco Medical Center.
Rebecca Clausen, an office worker in Durham, North Carolina, was prescribed several courses of a cheap oral antibiotic for a persistent UTI earlier this year, but it “just seemed to keep coming back,” she said. Doctors considered a six-week treatment with an intravenous drug, ertapenem, that would have cost her about $2,000 out-of-pocket, but decided it probably wouldn’t help. For now, she’s simply hoping the infection won’t worsen.
While specialists say they are seeing more urinary tract infections that oral antibiotics can’t eliminate, the problem is still thought to be relatively rare (federal health officials don’t directly track the issue). However, it’s emblematic of a failure in the antibiotics industry that experts and even U.S. senators say can be fixed only with government intervention.
The CDC report, released July 12, showed that after mostly declining during the previous decade, the incidence rates of seven deadly antimicrobial-resistant organisms surged by an average 15% in hospitals in 2020 because of overuse in COVID-19 patients. Some of the sharpest growth occurred in bugs that cause hard-to-treat UTIs.
Although nearly 50,000 Americans — and about 1.3 million people worldwide — die of resistant bacterial infections each year, the FDA has not approved a new antibiotic since 2019. Big Pharma has mostly abandoned antibiotics development, and seven of the 12 companies that successfully brought a drug to market in the past decade went bankrupt or left the antibiotics business because of poor sales.
That’s because of a central paradox: The more an antibiotic is administered, the quicker bacteria will mutate to get around it. So practitioners are aggressively curbing use of the drugs, with 90% of U.S. hospitals setting up stewardship programs to limit the use of antibiotics, including new ones. That, in turn, has caused investors to lose interest in the antibiotics industry.
A pipeline of new drugs is vital, given the implacable capacity of bacteria to mutate and adapt. But while resistance is an ever-present danger, some 90%-95% of fatal infections involve microbes that are not multidrug-resistant but difficult to treat for other reasons, such as the delicate condition of the patient, said Dr. Sameer Kadri, head of clinical epidemiology at the National Institutes of Health Clinical Center’s Critical Care Medicine Department.
“As bad as antibiotic resistance is, it’s bad against a minority of people,” said
Jason Gallagher, a professor and infectious diseases pharmacist at Temple University Hospital in Philadelphia. Since clinicians usually can’t quickly determine a bug’s resistance level, they start with the old drug most of the time. “That makes antiinfectives a pretty tough investment from a drug company perspective,” he added. “You’re going to develop your drug and people are going to do their best to not use it.”
As antibiotics companies disappear, so does their scientific expertise, said Dr. David Shlaes, a retired pharmaceutical industry scientist. Should a particularly deadly pattern of resistance develop with no drug pipeline, it could cause destruction on a hair-raising scale, he said.
“Antibiotics are an essential part of civilization,” said Kevin Outterson, a Boston University law professor who leads a public-private fund that helps companies develop antimicrobials. “They must be renewed every generation or we will slip back into the pre-antibiotic era.”
The roadblocks to approval of the UTI drugs tebipenem and sulopenem illustrate the complexity and regulatory challenges of the antibiotics arena.
In a big clinical trial completed last year, Iterum Therapeutics’ sulopenem was far better than an older drug, ciprofloxacin, at reducing UTI symptoms, but it didn’t seem as adept at killing bacteria, which the FDA considered to be an equally important measure of success. At a June 3 workshop, FDA officials indicated they might be willing to change their standard in future trials.
Another company, Spero Therapeutics, published what looked like a successful trial for oral tebipenem in the New England Journal of Medicine in April. But FDA officials rejected Spero’s application for licensure because a species of bacteria included in the analysis was deemed irrelevant to the drug’s efficacy.