Combining 4 or 5 antibiotics may help kill deadly bacteria

In a promising find, a team of biologists at the University of California-Los Angeles has discovered thousands of four-and five-drug combinations of antibiotics that are more effective at killing harmful bacteria than the prevailing views suggested. The findings, published in the journal npj Systems Biology and Applications, could be a major step toward protecting public health at a time when pathogens and common infections are increasingly becoming resistant to antibiotics.
Scientists have traditionally believed that combining more than two drugs to fight harmful bacteria would yield diminishing returns. “There is a tradition of using just one drug, maybe two,” said Pamela Yeh, one of the study’s senior authors.
“We’re offering an alternative that looks very promising. We shouldn’t limit ourselves to just single drugs or two-drug combinations in our medical toolbox. We expect several of these combinations, or more, will work much better than existing antibiotics,” added Yeh, Assistant Professor of Ecology and Evolutionary Biology.
Working with eight antibiotics, the researchers analysed how every possible four-and five-drug combination, including many with varying dosages— a total of 18,278 combinations in all — worked against E. coli. They expected that some of the combinations would be very effective at killing the bacteria, but they were startled by how many potent combinations they discovered.
For every combination they tested, the researchers first predicted how effective they thought it would be in stopping the growth of E. coli. Among the four-drug combinations, there were 1,676 groupings that performed better than they expected. Among the five-drug combinations, 6,443 groupings were more effective than expected.
“I was blown away by how many effective combinations there are as we increased the number of drugs,” said Van Savage, the study’s other senior author. On the other hand, 2,331 four-drug combinations and 5,199 five-drug combinations were less effective than the researchers expected they would be, said Elif Tekin, the study’s lead author who was a UCLA postdoctoral scholar during the research.
Yeh said although the results are very promising, the drug combinations have been tested in only a laboratory setting and likely are at least years away from being evaluated as possible treatments for people. The researchers are creating open-access software based on their work that they plan to make available to other scientists next year.