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article imageThree-drug cocktail could overcome antibiotic resistance

By Karen Graham     Jul 22, 2016 in Health
An interesting new study, using a combination of techniques from biology to mathematics has found that overcoming antibiotic-resistant bacterial infections could be achieved by using a three-drug cocktail, or combination of antibiotics.
Every year, according to the CDC, at least 2 million people in the U.S. become ill with antibiotic-resistant infections, and of that number, almost 23,000 people die. Worldwide, the figure is close to 700,000 deaths every year from these pathogens.
In the study conducted by UCLA life scientists and published in the journal Royal Society Interface, it was found that a combination of three different antibiotics often overcame the bacteria's resistance, even when on their own, or even in combinations of two, the antibiotics weren't effective.
Pamela Yeh  Elif Tekin and their UCLA colleagues plan to offer open-access software based on their w...
Pamela Yeh, Elif Tekin and their UCLA colleagues plan to offer open-access software based on their work that would let other scientists choose the most effective combinations of antibiotics.
UCLA
The research team grew Escherichia coli bacteria in the laboratory and treated samples with different combinations of one, two or three antibiotics from a core group of 14 commonly used antibiotics. The researchers studied and recorded the results from every possible drug combination used to kill the bacteria, and how effective they were.
According to Pamela Yeh, the paper’s senior author, and a UCLA assistant professor of ecology and evolutionary biology, some of the drug combinations killed 100 percent of the bacteria. This included 94 of the 364 three-drug groupings tested in the study. Yeh added that the success rate could have been even higher if they had used higher doses of antibiotics.
The paper's lead author, Elif Tekin, a UCLA graduate student, helped to create the mathematical framework that helped the scientists to decide when adding a third antibiotic was producing new effects that two-drug combinations were not achieving. And this elaborate framework is essential to helping clinicians to determine which combination of antibiotics will work best, the team found out.
"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."
Using antibiotic mechanisms is the key
Most people may not realize that not all antibiotics attack bacteria in the same way. Antibiotics are divided into three classes, based on the mechanism used to kill bacteria. One class that includes amoxicillin, kills bacteria by preventing them from making cell walls. This is called Cell Wall Synthesis.
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Ortho Bullets
The second class of antibiotics that includes Fluoroquinolones, and Ciprofloxacin, disrupt the tightly coiled DNA of bacteria. Drugs in this class are called DNA Synthesis Inhibitors. The third class of antibiotics inhibits the bacteria's ability to make proteins. This class includes drugs like Gentamycin and Tetracyclines.
"People tend to think that you don't need to understand interactions beyond pairs," said Van Savage, a co-author of the paper and a UCLA associate professor of ecology and evolutionary biology and of biomathematics. "We found that isn't always so."
The choice of the right combination of antibiotics is crucial, and must be a rational decision, says the research team. They found that some combinations didn't work at all, while other combos with just two antibiotics worked far better than if a third antibiotic was added.
The study concludes: We need a sound policy to stop the overuse of antibiotics, doctors to prescribe antibiotics wisely, agriculture to stop overusing antibiotics and researchers to develop new antibiotics. We need to attack this problem from all sides. We think our contribution will buy time for researchers to better leverage existing drugs and for policymakers to develop a better policy about the use of antibiotics.
The research team will be making available open-access software that would let other scientists and clinicians decide which combinations of antibiotics will be most effective.
The study, "Enhanced identification of synergistic and antagonistic emergent interactions among three or more drugs." was published in the Journal of the Royal Society Interface.
More about Antibiotic resistance, threedrug combo, disruption of mechanisms, interactions, major public health risk
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