Combating drug-resistant bacterial infections

Every year, around 700,000 people die from drug-resistant bacterial infections. A recent study by UCLA life scientists could be a major step toward combating drug-resistant infections.
The study found that combinations of three different antibiotics can overcome bacteria's resistance to antibiotics, even when none of the three antibiotics on their own--even two of the three together--is effective. The scientists 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. The success rate might have been even greater if the researchers tested higher dose of the drugs. 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. 

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. 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 with less potent -- sometimes much less. The results could be one weapon to fight what has become a major public health risk, but overcoming drug resistance will require a full arsenal.

We need sound policy to stop the overuse of antibiotics, doctors prescribe antibiotics wisely, agriculture to stop overusing antibiotics and researchers to develop new antibiotics. We need to attack this problem from all sides. This contribution will buy time for researchers to better leverage existing drugs and for policy makers to develop better policy about the use of antibiotics.

Another benefit of three-drug combinations is that they could allow doctors to prescribe lower doses of each antibiotic, which could reduce side effects. The researchers plan to make available open-access software that would let other scientists and clinicians decide which combinations of antibiotics will be most effective.