How compounds are being used as an adjuvant to energize conventional antibiotics, and make them more effective

Drug-resistant microbes are becoming a global crisis. Last week, Eureka featured a story about the spread of Candida auris, a lethal yeast infection, in hospitals.  The microbe is both difficult to detect and to treat, and with more than 600 cases reported in the US alone, the US Centers for Disease Control and Prevention considers the emerging fungus a serious global health threat.

The threats don’t stop there. We are awash in bugs that we don’t know how to control. Experts predict that by 2050, about 10 million people a year will die of antibiotic-resistant infections. Children are particularly vulnerable. A recent study published last year in the Journal of the Pediatric Infectious Diseases Society, found that 3 out of 5 children admitted to hospitals already had an antibiotic-resistant infection, suggesting these infections are spreading more often in the community right now.

But the elderly and peoples with conditions that compromise their immune systems are perhaps the most vulnerable.

On the plus side, researchers are making real headway in the search for next-generation solutions. One such idea is using novel compounds, called antibiotic resistance breakers (ARBs), with conventional antibiotics to restore the potency of the drug.  A recent article appearing in the journal Future Drug Discovery describes how the biopharmaceutical company Helperby Therapeutics Group Ltd is using this strategy to combat drug resistance.

In an interview with the journal, Anthony Coates, a founder of the company, said they have developed an ARB-antibiotic combination effective against three pathogens that the World Health Organization considers among the most dangerous—Acinetobacter baumanniiPseudomonas aeruginosa and Enterobacteriaceae—and they currently have two combinations in mid- to late-stage clinical trials. “Antimicrobial resistance is one of the most pressing global threats to medicine,” Coates told Future Drug Discovery. “Without effective antibiotics, much of the success of modern medicine, such as the levels of unprecedented survival rates from major surgery or chemotherapy treatment, would be severely compromised.”

ARBs are not antibiotics. They are compounds that when co-administered with antibiotics act to block resistance or enhance antimicrobial activity, in the same way that adjuvants boost the potency of vaccine candidates.  With the development of new antibiotics not occurring fast enough, this strategy is seen as a way of recharging older antibiotics whose effectiveness has waned against deadly pathogens. Coates recently began collaborating with Pamela Yeh’s lab at UCLA, which independently has found that combinations of four and even five drugs can potentially  help protect the public against resistant infections. A primary goal of the collaboration is to explore commercial opportunities.

Coates told Future Drug Discovery that he believes that using ARBs will not only increase efficacy of antibiotics, they will broaden the spectrum of treatments against tough-to-treat pathogens. “In my opinion, I think this could be the most important breakthrough in the fight against antibiotic resistance.”

There are also other strategies afoot to combat drug-resistant infections. Phage therapy, the subject of a three-part series on Eureka in January 2018, uses bacteria-eating viruses as an alternative treatment for certain infections. Other strategies target resistance mechanisms, such as enzyme inhibitors and inactivating the genes that encode for resistance mechanisms. The development of preventive vaccines is also an active area of research.

Will we eradicate the germs? Unlikely. Drug-resistant bugs will keep marching on, but with the proper weapons maybe some of them will capitulate like the GOT’s Night King.