Combinations of three different antibiotics can overcome bacteria’s resistance to antibiotics, even when none of the three drugs on their own – or even two of the three together – is effective, scientists have found.
Each year, approximately 700,000 people die from drug-resistant bacterial infections, researchers said. They grew E coli bacteria in a laboratory and treated the samples with combinations of one, two and three antibiotics from a group of 14 drugs.
The biologists studied how effectively every single possible combination of drugs worked to kill the bacteria. Some combinations killed 100 per cent of the bacteria, including 94 of the 364 three-drug groupings the researchers tested.
According to Pamela Yeh from the University of California, Los Angeles (UCLA), the success rate might have been even greater if the researchers tested higher doses of the drugs.
Elif Tekin, UCLA graduate student, helped create a sophisticated framework that enabled the scientists to determine when adding a third antibiotic was producing new effects that combinations of just two drugs could not achieve.
“Three antibiotics can change the dynamic. Not many scientists realise that three-drug combinations can have really beneficial effects that they would not have predicted even by studying all pairs of the antibiotics together,” she said. Different classes of antibiotics use different mechanisms to fight bacteria. One class, which includes amoxicillin, kill bacteria by preventing them from making cell walls. Another disrupts their tightly coiled DNA.
A third inhibits their ability to make proteins. But there had been little previous research indicating that combinations of three antibiotics might be more potent together than any two of them.
“People tend to think that you don’t need to understand interactions beyond pairs. We found that is not always so,” said Van Savage, a UCLA associate professor. The researchers combined techniques from biology and mathematics to determine which groups of antibiotics would be most effective. “The three antibiotics must be chosen systematically and rationally,” Yeh said.
In addition to identifying certain combinations that were more potent than the researchers expected, the analysis showed that adding a third antibiotic sometimes made the drug combination less potent – sometimes much less so, she said.
Yeh said the findings could be one weapon to fight what has become a major public health risk, but overcoming drug resistance will require a full arsenal.
The study was published in the journal Royal Society Interface.