Have some pity for your ancestors. Prior to the remarkable medical advances of the past hundred years or so, life was nasty, brutish, short and utterly terrifying — it’s a wonder anybody ever left the hovel. Sexually transmitted diseases were incurable and often fatal, up to 25 percent of mothers died in childbirth and a scrape could lead to a deadly infection. Thankfully, the Age of Antibiotics dawned in 1928 when Alexander Fleming fooled around with some mold juice at a London hospital and ended up with penicillin, transforming medicine and vastly improving the lives of billions. But humanity now is teetering on the edge of a new era: the Age After Antibiotics, as increasing numbers of bacteria develop resistance to increasing numbers of drugs.
The overprescription of antibiotics and their use in animal husbandry to promote growth have both contributed to the problem: Bacteria that survive unnecessary or improper antibiotic use can mutate into strains that drugs can’t touch. In the U.S. alone, 2 million infections and 23,000 deaths annually are directly attributable to drug-resistant bacteria — “and both of these are conservative estimates,” says Jean Patel, director of the Centers for Disease Control and Prevention’s Office of Antimicrobial Resistance. One of the “urgent threats” identified by the CDC is a family of bacteria called CRE (technically, carbapenem-resistant Enterobacteriaceae), which is developing resistance to colistin, the “drug of last resort,” Patel says. Oh, and don’t expect big pharma to bail us out: Drug manufacturers are reluctant to plow money into developing new antibiotics when the targeted bugs are likely to develop resistance to them within months.
Are you scared yet? The medical community is. Scientists are scrambling to find solutions to this urgent public health concern, and some new research suggests a surprising potential solution: even more antibiotics.
A team of UCLA researchers led by Elif Tekin, a Ph.D. graduate student, and Pamela Yeh, an assistant professor of ecology and evolutionary biology, found that certain combinations of three or more antibiotics can work together to kill bacteria more effectively than just one or two of the drugs. These so-called “emergent synergistic interactions” are “something very novel that we didn’t expect,” Yeh says, and “might be especially relevant and especially useful” in the fight against antibiotic resistance. What’s more, Tekin explains, it’s not just about overcoming drug resistance; it’s also about increasing the efficiency of individual drugs at lower concentrations in order to reduce or eliminate side effects.
Multidrug cocktails might not sound synonymous with good health, but they’re already an established treatment for HIV and other viral infections, designed to decrease the chances that some of the virus might survive the pharmacological onslaught. Antibacterial drugs, meanwhile, “have traditionally been so incredibly potent that combinations of antibiotics, although not unheard of, are certainly not the norm,” says Gerry Wright, professor of biochemistry and biomedical sciences at McMaster University in Hamilton, Ontario. Wright’s research focuses on how molecular compounds can team up with antibiotics to tackle infections even more effectively.
“We really don’t understand in many cases how antibiotics work at the molecular level,” Wright says, which is somewhat surprising given how central these drugs are to modern medicine. So it’s difficult to know which combinations will work and why. Tekin and Yeh’s research includes a mathematical model to analyze precisely how these combinations of antibiotics collaborate, which eventually may help drug manufacturers predict the interactions in cocktails of three or more drugs. Researchers do know that antibiotics attack bacteria in different ways, one of which is to make it more difficult for them to build new cell walls as they replicate and grow. One synergistic one-two punch, then, involves a cell wall-inhibiting drug that lets another drug sneak into bacterial cells more easily.
It could be that the problem is going to get worse before it gets better.
Jean Patel, director, CDC Office of Antimicrobial Resistance
But we’re not about to launch the Age of Antibiotics 2.0, at least not yet. Tekin and Yeh are quick to note that “we are not physicians.” Indeed, the UCLA team’s research took place in a petri dish, far from any patient. “Testing just one E. coli organism in a test tube is not predictive of what happens in the real world,” says Dr. Lee Riley, professor of epidemiology and infectious diseases at the University of California, Berkeley School of Public Health. Indeed, there are a great deal of complications that can come with turning drugs that are promising in the lab into a safe and effective pill for humans, including making sure that the chemicals arrive at the infection in the right concentration. That challenge becomes even more difficult when the treatment includes administering two, three or four drugs at once.
And what happens if antibiotic cluster bombs eventually create super-duper-resistant bacteria? “It’s a fair concern,” says Wright, but “I think we have to calibrate that against the fact that we don’t have a big cupboard full of fancy new drugs to address [resistance] in another way. You can never forestall evolution completely, but you can buy yourself a significant amount of time.”
And indeed, across the medical community, all sorts of research are zeroing in on this issue, including the development of antibacterial vaccines, novel therapies such as controlling viruses to kill bacteria and new preventative treatments that harness the power of the beneficial bacteria living in your gut. In the end, it’s a race to see which, if any, of these new treatments will be ready to fight the resistant bugs emerging today. For the CDC’s Patel, “it could be that the problem is going to get worse before it gets better.”