TEDMED: Andrew Read’s Five Tips For Keeping Superbugs At BayResearchers may like to think they’re pretty smart, but you could argue that bacteria have also got some bragging rights. Every day, microbes develop resistance to even the most powerful antibiotics scientists have developed.
“Picking a fight without Darwin is like going to the moon without Newton,” Read added. “We are in the dark ages when it comes to evolutionary management.”
Read, director of Penn State University’s Center for Infectious Disease Dynamics, sat down with me on Thursday and shared a few principles he thinks the scientific community should keep in mind in order to keep antibiotic resistance in check. Here are his five tips for would-be superbug slayers.
Get smart with the drugs you’ve already got.
“We can’t rely on a continual supply of new drugs,” Read said. Many firms have already exited antibiotic research, he notes. “You can see that the markets aren’t good enough right now to drive innovation,” since new antibiotics are precious and used only for patients’ most severe infections rather than being prescribed widely. Read says firms should continually evaluate dosing and combination strategies with established drugs in order to stave off resistance. “I’m not saying we shouldn’t discover new antimicrobials,” Read stressed. “In some situations, like malaria, it’s really critical. But we don’t want to put all our eggs in that basket.”
Learn from what works.
“I think magic bullets are the exception rather than the rule,” Read says. But researchers should focus on why wildly successful therapies were so. “Why was that pathogen unable to get around the smallpox vaccine? Why is chloroquine still working against some malarias in some parts of the world when it’s has failed miserably in others?” Read asked.
Make the right matches for combination therapies.
Read notes that some antimalarial drug combinations have consisted of drugs with markedly different half-lives. In effect, once the first drug has left the human body, all that’s left is the other drug, a monotherapy. “And that’s dangerous,” a breeding ground for resistance, Read cautions. “You want to be combining drugs that have similar half-lives.” Researchers should also think about whether their antibiotics become more lethal to microbes when used in combination, or less lethal, Read says. Evidence suggests that less lethal is better, he says. According to work from Roy Kishony’s lab at Harvard Medical School, if an antibiotic combo is less lethal, once resistance develops to one drug (call it drug A) in the pair, then drug B can kick in, stronger than before, to kill off microbes that remains.
Consider your consequences.
Approaches that tame pathogens’ toxins haven’t yet reached the market, but are an active area of research (Nature Rev. Microbiol., DOI: 10.1038/nrmicro1818). “From an evolutionary point of view, they are extraordinarily interesting drugs, but possibly quite dangerous,” Read says. Why? Well, “it could go one of two ways,” Read explains. “The bacterial might not bother with the toxin, which would be good. Or it could try to overproduce and overwhelm the new drug, which would be bad.”
Invest in evolution management.
Antibiotic drug development, like development of any new drug, is a long, expensive slog, and Read thinks some of the resources could use redirection. “We get this thing at the end that’s taken us 12 years and a gazillion bucks. How much money did we put into figuring out how to make the damn thing work for much longer- maybe one tiny grant?” he says. “The work’s only just begun when you’ve got the drug.”