Students walk in front of the Pauley Pavilion on the campus of UCLA in Los Angeles. Photo by John Schreiber.
Students walk in front of the Pauley Pavilion on the campus of UCLA in Los Angeles. Photo by John Schreiber.

Combinations of three different antibiotics can often overcome bacteria’s resistance to antibiotics, even when none of them drugs on their own — or even two of the three together — is effective, according to a study released Thursday by UCLA life scientists.

Each year, about 700,000 people die from drug-resistant bacterial infections. The results of the study, reported in the journal Royal Society Interface, could be a major step toward combating those infections, according to UCLA.

The researchers 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 percent of the bacteria, including 94 of the 364 three-drug groupings the researchers tested.

According to Pamela Yeh, the paper’s senior author and a UCLA assistant professor of ecology and evolutionary biology, the success rate might have been even greater if the researchers tested higher doses of the drugs.

Elif Tekin, the study’s lead author and a 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 couldn’t achieve.

“Three antibiotics can change the dynamic,” she said. “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.”

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, according to the UCLA team.

“People tend to think that you don’t need to understand interactions beyond pairs,” said Van Savage, a UCLA associate professor of ecology and evolutionary biology and of biomathematics. “We found that isn’t always so.”

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 revealed that adding a third antibiotic sometimes made the drug combination less potent — sometimes much less so, she said.

–City News Service

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