For the first few decades after penicillin’s introduction, bacterial adaptation and drug discovery leapfrogged each other, keeping antibiotics’ ability to treat infections in front of pathogens’ skill at evading them. But by the 1970s, that midcentury burst of innovation had faded. Making antibiotics is hard: the drugs have to be nontoxic to humans but lethal to bacteria, and they must use mechanisms that dangerous bacteria haven’t yet evolved defenses against. But moving from antibiotics produced in nature to synthesizing compounds in a lab was even harder.
Resistance, meanwhile, leaped ahead. Overuse in medicine, agriculture, and aquaculture spread antibiotics through the environment and allowed microbes to adapt. Between 2000 and 2015, use of the antibiotics that have been reserved for the most lethal infections almost doubled worldwide. Levels of resistance differ by organism, drug, and location, but the most comprehensive report done to date, published in June 2021 by the WHO, shows how fast the situation has changed. Among the strains of bacteria that cause urinary tract infections, one of the most common health problems on the planet, some were resistant to a common antibiotic up to 90% of the time in certain countries; more than 65% of the bacteria causing bloodstream infections and more than 30% of the bacteria causing pneumonia resist one or more treatments as well. Gonorrhea, once an easily cured infection that causes infertility if left untreated, is rapidly developing resistance to all the drugs used against it.
At the same time, resistance factors—the genes that control bacteria’s ability to protect themselves—are traveling the globe. In 2008, a man of Indian origin was diagnosed in a hospital in Sweden with a strain of bacteria carrying a gene cluster that allowed it to resist almost all existing antibiotics. In 2015, British and Chinese researchers identified a genetic element in pigs, pork in markets, and hospital patients in China that allowed bacteria to defuse a drug called colistin, known as an antibiotic of last resort for its ability to tackle the worst superbugs. Both those genetic elements, hitchhiking from one bacterium to another, have since spread worldwide.
In the face of drug development’s difficult economics, antibiotic research has not kept up. In March, the Pew Charitable Trusts assessed the global pipeline of new antibiotic compounds. Though the group found 43 somewhere in preclinical or clinical research stages, it determined that only 13 were in phase 3, only two-thirds of those would be likely to make it through to licensure—and none possessed the molecular architecture to work against pathogens that are already the most difficult to treat.
Lessons from Warp Speed
So what would an Operation Warp Speed for antibiotic resistance look like?
The antibiotic pipeline needs a boost in several key areas: basic research, trial design, and post-approval incentives. Fortunately, the global response to covid created precedents for all three.
The first step would be supporting basic research in the long term. The Moderna and Pfizer-BioNTech vaccines were ready to go less than a year from the first recognition of human infections. But that readiness came from 10 years of basic research with no specific disease in mind. Once covid appeared, Warp Speed brought the Moderna vaccine to the finish line with extra research funding. (Pfizer didn’t receive research support from Warp Speed, but both companies got funds for manufacturing and production.)