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A cocktail of antibiotics could be more than the sum of its parts in the fight against drug-resistant bacteria. New study reveals that mixing three to five types of antibiotics can increase efficiency … sometimes.
More than 8,000 combinations of four and five drugs tested in the new study were more effective than expected based on their individual actions. Despite this, "antagonistic interactions" – that combined drugs were less effective than expected – became more frequent as the number of combination drugs increased.
Studying how only two drugs combine to interact "is very complicated, so people have not really examined these higher order interactions," said Pamela Yeh, professor of ecology and psychology. Evolutionary Biology at the University of California at Los Angeles. and co-author of the study. [6 Superbugs to Watch Out For]
The new research shows that interactions involving three, four or five drugs are more important than previously thought, Yeh said.
Beat the superbugs
However, it is unclear whether multi-drug cocktails will be a real solution for infections that are resistant to traditional antibiotic treatments. The research studied antibiotics only in laboratory dishes, and she did not ask important medical questions such as how side effects of the drugs might change depending on the number of antibiotics used.
The goal was to use bacteria and antibiotics as a small controlled ecosystem to study the interactions between stressors, said study co-author Van Savage, professor of ecology and evolutionary biology. at UCLA. In a real-world ecosystem, stressors can be a combination of factors such as precipitation, temperature changes, invasive species and more. In combination, each of these factors could affect others, and the interactions are not always intuitive, said Savage Live Science.
"It's easy to take things apart and study them," said Savage. "It makes sense as something to do, but when you gather them together, you have to make sure to put them together in the right way."
The researchers tested eight antibiotics: ampicillin, cefoxitin, sodium salt, ciprofloxacin hydrochloride, doxycycline hyclate, erythromycin, sodium salt of fusidic acid , streptomycin and trimethoprim. These were chosen because they all have different ways of attacking bacteria. All combos of two, three, four and five drugs were mixed with E. colibacteria in laboratory dishes at several different doses, for a total of 18,278 separate experiments.
The researchers used bacterial growth rates to evaluate the effectiveness of the combinations. If two or more antibiotics did not interact with each other, the impact on the bacterial growth rate would be the same as the multiplication of the effects of each antibiotic between them; For example, two antibiotics would work twice as effectively, and three antibiotics would work three times more effectively. If the antibiotics worked synergistically, the impact on the growth rate would be greater than this reference level; if they oppose each other antagonistically, the impact would be less.
In 1,676 cases with four drugs and 6,443 with five drugs, the antibiotics proved to be synergistic. The drugs killed the bacteria more efficiently than one would have expected if they simply worked side by side without interaction.
Complex interactions
The researchers expected that the more drugs enter the mix, the less the additional interactions matter, Savage said. Essentially, they expected the first interactions between drugs to be the most important. But that's not what they've seen.
"When we look at three, four or five drugs, new things happen [that are different] than what you expect based on what you see in pairs, "said Savage.
But more and more antibiotics were not always better, even though they attacked bacteria in different ways. As the number of drugs has increased, antagonistic interactions have increased. As a result, some of the drug combinations gave lower than expected results for individual drugs.
Bacterial resistance is a big problem in the real world, so Dr. Yeh said researchers hope their work will have an impact on future medical research. Bacteria evolve into defenses when they are exposed to antibiotics. The weakest strains are eliminated, while the resistant strains thrive.
As a result, disease control and prevention centers are identifying three drug-resistant strains of bacteria that pose an urgent threat to human health: Clostridium difficilewhich can cause life-threatening inflammation of the colon; carbapenem resistant Enterobacteriaceae, which primarily infects inpatients and nursing home residents; and drug resistant Neisseria gonorrhoeae, a sexually transmitted infection. A dozen antibiotic-resistant bedbugs are considered serious threats, according to the CDC.
The results of the new study are important because they show that the effect of the mixture of antibiotics is not always intuitive, according to the researchers. Combinations of medications may be less effective than one, or they may exceed expectations based on the expected results of adding the effects of each.
"We need to be very careful at all times when you are facing multiple stressors as they interact, and they do not interact exactly as we expected," Yeh said.
The results were published on September 3 in the journal npj Systems Biology and Applications.
Originally published on Science live.
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