A team of UCLA scientists has identified a cocktail of three different drugs that, while unable to treat resistant bacterial infections on their own, could be combined to overcome resistance of these life-threatening pathogens to antibiotics, according to a recently-published study.

In fact, they tested the effectiveness of various one, two and three-drug combinations in treating lab-grown E. coli bacteria, and found that 94 out of 364 three-drug groupings killed 100% of the bacteria, senior author Pamela Yeh, an assistant professor of ecology and evolutionary biology at UCLA, and her colleagues reported in the Journal of the Royal Society Interface.

Furthermore, in a statement, Yeh’s team reported that the success rate of the three-drug combos may have been even more effective had they tested higher doses of the medications. Even so, the findings provide new hope for the nearly 700,000 people who die each year due to infection from drug-resistant bacteria, including carbapenem-resistant Enterobacteriaceae such as E. coli.

“Three antibiotics can change the dynamic,” said lead author Elif Tekin, a graduate student at the university. “Not many scientists realize that three-drug combinations can have really beneficial effects that they would not have predicted even by studying all pairs of the antibiotics together.”

One piece of the puzzle, but other steps still need to be taken

Tekin, Yeh and their fellow researchers selected their antibiotic combinations from a group of 14 different drugs, choosing each using a sophisticated framework that allowed them to determine if adding a third drug into the mix produced new effects that two-drug pairings could not achieve.

Since different classes of antibiotics combat bacterial infections using different mechanisms, the team used both biological and mathematical techniques to discern which combinations would be the most effective. The three medications had to be selected “systematically and rationally,” Yeh said, and required determining if adding a third drug made the treatment more or less effective.

She also noted that three-drug combinations could allow doctors to prescribe lower doses of each antibiotic, which would reduce the risk of side effects in the patients. However, Yeh also warned that, while her team’s findings could help combat antibiotic resistance, other steps still needed to be taken in order to fully battle the increasing risk of these drug-resistant superbugs.

“We need to attack this problem from all sides,” she explained. “We need sound policy to stop the overuse of antibiotics, doctors to prescribe antibiotics wisely, agriculture to stop overusing antibiotics and researchers to develop new antibiotics,” Yeh added. On the plus side, however, she and her colleagues “think our contribution will buy time for researchers to better leverage existing drugs and for policymakers to develop better policy about the use of antibiotics.”

The researchers plan to release open-access software that will enable other scientists and doctors to review their methods and determine which antibiotic combinations will most effectively treat individual patients. They added that their approach could also be adapted to review the how four different medications interact, and could even be altered for use in non health-related fields.

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