‘We have arrived in the post-antibiotic era’: WHO warns of too few new drugs for deadly superbugs

Late last year, one of Dr. Vance Fowler’s patients — a man in his 60s who’d returned to North Carolina from visiting his family in Nepal — died of a bacterial infection. He’d been treated at a top U.S. hospital with access to the strongest antibiotics. But the infection, a drug-resistant strain of E. coli, surged on.

“Antibiotic resistance is a real problem that, with little or no warning, can affect the lives of any of us at any time,” said Fowler, an infectious disease specialist at Duke Health. “We don’t have enough drugs.”

Health officials have warned the public about antibiotic resistance for decades. That’s become more urgent in light of an upcoming World Health Organization report tallying only a handful of new antibiotics in development.

Preliminary data from the report, released by the WHO this month, paint a dire picture: Just 27 new antibiotics for the most threatening infections are in the clinical trial stage of drug development. In contrast, there were more than 1,300 cancer drugs in clinical trials in 2020, according to a report from the trade organization Pharmaceutical Research and Manufacturers of America.

Of the antibiotics in trials, the WHO considers only six of them innovative enough to overcome antibiotic resistance, and just two capable of targeting the most resistant bacteria. Agency officials will present the full report during the European Congress of Clinical Microbiology and Infectious Diseases next month.

There’s no telling whether this handful of new drugs in clinical trials will work, either. Between 2017 and 2021, just one new antibiotic, cefiderocol, was approved that could treat the superbugs on WHO’s most critical list, including strains of Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae. These pathogens can cause a range of potentially severe infections in the lungs, urinary tract, ears, blood, open wounds, or even the brain and the spinal cord.

Resistance on the rise

Drug-resistant bacteria are growing more common. In the United States alone, the Centers for Disease Control and Prevention estimates more than 2.8 million people develop drug-resistant infections each year, and more than 35,000 people die as a result. Certain drug-resistant strains of gonorrhea are on its list of urgent superbugs, as is Clostridioides difficile, or C. diff, which can cause life-threatening diarrhea and colon inflammation. The CDC estimates 12,800 people die of C. diff each year.

One of the most common superbugs in the U.S., methicillin-resistant Staphylococcus aureus, or MRSA, kills 9,800 people each year. MRSA can spread rapidly in long-term care facilities and hospital settings, where cases spiked 13% during the first year of the Covid pandemic.

Infections from the drug-resistant Shigella bacteria, often resulting in severe diarrhea and stomach pain, have been climbing at an alarming rate, too. In February, the CDC warned that last year, 5% of Shigella infections were “extensively drug-resistant” — meaning they didn’t respond to a number of antibiotics — up from zero percent in 2015. Shigella can spread through sexual contact, particularly among men who have sex with men.

Bacteria aren’t the only culprit. In the U.S., antifungal drug-resistant infections from the fungus Candida auris increased 60% in 2020, according to the CDC.

The WHO has identified 12 resistant superbugs deemed “priority pathogens,” and the CDC tracks a list of 18 drug-resistant bacteria and fungi.

Globally, more than 5 million people die from antibiotic resistance, outnumbering deaths from HIV, tuberculosis and malaria combined, said Valeria Gigante, the team lead of WHO’s antimicrobial resistance division.

“Antimicrobial resistance is one of the top global health threats facing humanity,” she said. “We shouldn’t call it a silent pandemic anymore. We should be loud and clear: it is indeed a pandemic.”

Bacteria and fungi are more likely to develop resistance the more they’re exposed to antibiotics or antifungals. In the case of Fowler’s patient, the specific E. coli bacteria strain had a gene that makes a protein called NDM-1, which can break down even the strongest, last-resort antibiotics, called carbapenems. Right now, most E. coli strains — there are more than 700 — aren’t deadly. But beyond E. coli, several strains of Klebsiella, Enterobacter and Acinetobacter already have this gene, and according to Fowler, more may soon acquire it.

“They don’t need a passport to travel,” Fowler said. And bacteria can swap DNA “kind of like baseball cards.”

“Maybe five or 10 years down the road, the U.S. will be facing resistance patterns reasonably similar to what we’re facing in India or Greece,” said Dr. Venkatasubramanian Ramasubramanian, president of the Clinical Infectious Diseases Society of India. Both countries have seen outbreaks of bacteria resistant to the strongest, last-resort antibiotics. “It’s a matter of time.”

The WHO says the rate of antibiotic resistance is accelerating. From 1970 to 2000, the average time it took for resistance to develop to new antibiotics was just two to three years, down from the 11-year average from 1930 to 1950. Resistance skyrocketed during the early days of the pandemic when many health systems overused antibiotics, which have no impact on Covid because it is caused by a virus, not a bacterium.

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