To help tackle the growing problem of antibiotic resistance, scientists have come up with more than 8,000 new antibiotic combinations that have proved surprisingly effective at tackling harmful bacteria.
It's surprising because mixing multiple drugs together often has less of an impact rather than more: they can cancel each other out, or provide very little extra benefit in fighting infection.
However, biologists from the University of California in Los Angeles (UCLA) have used a methodical testing system to identify these thousands of new mixes, combining four or five drugs at a time. It's early days but this method could buy us some time in the fight against antibiotic-resistant bugs.
"There is a tradition of using just one drug, maybe two," says one of the team, Pamela Yeh. "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."
The researchers started with eight antibiotics and ran through every four and five-drug combination to test its effectiveness against Escherichia coli. In total they experimented with 18,278 separate combinations, including varying doses of each drug.
In the list of four-drug combinations, 1,676 performed better than expected; a total of 6,443 five-drug combinations also exceeded expectations in fighting E. coli.
By comparison, 2,331 of the four-drug combinations and 5,199 of the five-drug combinations were less effective at fighting the infection than the scientists anticipated.
"I was blown away by how many effective combinations there are as we increased the number of drugs," says one of the researchers, Van Savage.
"People may think they know how drug combinations will interact, but they really don't."
Part of the reason, the scientists think, is that different drugs attack bacteria in different ways. The eight drugs they picked cover six different mechanisms for tackling E. coli, and in some cases that seems to be more effective than a single approach.
"Some drugs attack the cell walls, others attack the DNA inside," says Savage. "It's like attacking a castle or fortress."
While the study offers new hope in tackling the problem of antibiotic resistance, actual treatments could still be years off – this research only shows potential effects in a laboratory setting, and only against E. coli.
And it's not just a question of throwing together any type of drug: they need to be carefully and systematically chosen to treat particular problems, the researchers say.
Previous research has found that using multiple antibiotics at once can backfire, making bacteria even more aggressive – so while this new research is encouraging, it should be noted that it needs to be used with caution.
With health organisations around the world continuing to sound serious warnings about the threat of antibiotic resistance, it's clear we need all the help we can get. If we can't find new antibiotic fixes for common bugs, they might claim as many as 10 million lives a year by 2050, the World Health Organisation reports.
According to Michael Kurilla, director of the Division of Clinical Innovation at the National Institutes of Health, who wasn't involved in the latest study, the new research can be used as a foundation for further research into multi-drug combinations.
"With the spectre of antibiotic resistance threatening to turn back health care to the pre-antibiotic era, the ability to more judiciously use combinations of existing antibiotics that singly are losing potency is welcome," says Kurilla.
The research has been published in npj Systems Biology and Applications.