San Diego
Each year, more than 2 million people in the United States get antibiotic-resistant infections, according to the Centers for Disease Control and Prevention. At least 23,000 of them die. Unless breakthroughs are achieved, that toll will keep rising.
If a new version of an antibiotic of last resort lives up to its promise, that date with doom may be averted. A study on this bolstered form of vancomycin by scientists at the Scripps Research Institute was released Monday.
Researchers led by Dale Boger, co-chair of Scripps’ Department of Chemistry, introduced three modifications to vancomycin, all lethal to bacteria and independent of each other. Superbugs need to overcome all three changes to survive, which is extremely unlikely, the study said.
The study was published in the Proceedings of the National Academy of Sciences. Boger was senior author and Akinori Okano, also of Scripps, was first author. Research funding was supplied by the National Institutes of Health.
While fear of losing antibiotics has made doctors restrict their use, Boger and colleagues contend that doesn’t solve the problem, it just slows the process. Better science is the solution, they say, to engineer antibiotics to anticipate and thwart resistance from the start.
The modified vancomycin needs further development so it can be tested in people to prove its safety and efficacy. Moreover, Boger’s team made the drug through a lengthy, 30-step process, which limits yield. He and colleagues are working on shortening that process.
Even with the current synthesis method, the new vancomycin should be medicinally useful, the study said. It’s more than 10 times as potent as an earlier version that introduced two lethal modifications.
With the third lethal change, the altered vacomycin is more than 1,000 times as potent as standard vancomycin.
Bacteria exist in astronomical numbers, mutate often and freely swap genes with others, even between species. So when they’re confronted with antibiotics, Darwinian evolution by natural selection ensures that when resistance occurs even once, it rapidly spreads.
Vancomycin foiled this evolution for decades because it indirectly attacks bacteria by removing oligopeptide, a substance needed for their survival. But even so, some bacteria have developed resistance.
This process has spurred the rise of vancomycin-resistant enterococci, or VRE, three letters that strike fear into hospital staffs the world over.
VRE has spread relentlessly, despite the best efforts of medical professionals.
Given the power of natural selection, the emergence of VRE and other resistant organisms appears inevitable.
So doctors have become more cautious in prescribing antibiotics, hoping to reduce the pressures of natural selection that fuel resistance.
Boger and colleagues say in the study that approach is too defeatist.
“Although sounding attractive, the effort to restrict antibiotic use seems counter to their importance, introduces guilt into even their most legitimate of uses, challenges the prevailing practices of initial empirical best guess therapy and prophylaxis deployment, and produces additional disincentives to antibiotic development,” the study says.
Moreover, restricting antibiotic use doesn’t do anything to generate greater understanding of how resistance arises and how it might be thwarted, it said.
And the study posed a question:
“As an alternative to championing the restricted use of antibiotics or conceding that bacteria will always outsmart us, can durable antibiotics be developed that are capable of continued or even more widespread use?”
The modified vancomycin provides a positive answer, the authors say, not only by itself, but also as an approach to generating other more durable antibiotics.