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To eradicate infection in a polymicrobial setting, higher doses are required

To eradicate infection in a polymicrobial setting, higher doses are required

A study showed that antibiotics needed to kill bacterial infections of the airways are more effective than those used for other microbes. This helps to explain why respiratory infections can persist in patients with lung diseases like cystic fibrosis, despite treatment.

In the study, published today The ISME JournalResearchers have found that even a small amount of one type can have a profound influence on the response of other microbes to antibiotics.

These results demonstrate the importance of considering the interactions between different types of microbes when treating infection with antibiotics.

“People with chronic infection often have co-infections with multiple pathogens. However, we don’t take this into consideration when deciding how many antibiotics to use. Our findings might help explain why these people aren’t getting the antibiotics they need,” said Thomas O’Brien who conducted the research for his PhD at the University of Cambridge’s Department of Biochemistry. He is also the joint first author of this paper.

It is very difficult to treat chronic bacterial infections like those in the airways. These infections are often caused by one pathogenic species. However, many other microbes are present at the same time.

Most treatment options focus on the pathogen and do not consider co-habiting species. These treatments are often unsuccessful in eradicating the infection. Scientists have not been able to understand why this happens.

To achieve their results, the team designed a simplified model for the human airways that contained artificial sputum (“phlegm”), which was chemically identical to the real phlegm produced by an infection.

They were able to grow a variety of microbes, including pathogens in a stable manner for several weeks using this model. This is very unusual, as most pathogens will outgrow each other quickly and ruin the experiment. Researchers were able to reproduce and study multiple microbes in the laboratory, a technique known as ‘polymicrobial infections’.

The bacteria, the yeast and the microbes were used in the experiment. Pseudomonas aeruginosa And Staphylococcus aureus, The fungus Candida albicans – a combination commonly present in the airways of people with cystic fibrosis.

The researchers used colistin, an antibiotic that is very effective in killing bacteria, to treat the microbial mix. Pseudomonas aeruginosa. However, the other pathogens were also present Pseudomonas aeruginosa, The antibiotic didn’t work.

We were shocked to discover that an antibiotic we know could clear an infection Pseudomonas In other words, it didn’t work in the lab model even though there were other bugs.

Wendy FigueroaChavez (University of Cambridge’s Department of Biochemistry), was the first author of the paper.

The same effect happened when the microbial mix was treated with fusidic acid – an antibiotic that specifically targets Staphylococcus aureus, Fluconazole and fluconazole Antibiotic that targets specific groups Candida albicans.

Researchers found that antibiotics needed to kill bacteria in poly-microbial infections required significantly higher amounts of each antibiotic than when there were no other pathogens.

Martin Welch (Professor of Microbial Physiology and Metabolism at the University of Cambridge and senior writer of the paper) stated that “all three species-specific antibiotics were less effective against the target when three pathogens existed together.”

Antibiotics are currently only laboratory tested against the pathogens they are intended to treat. This allows for the determination of the lowest effective dose. This study explains why the same dose of antibiotics is not effective in treating infection in people. The new model system will allow potential new antibiotics to test against a variety of microbe species.

People with cystic fibrosis are more likely to have poly-microbial infections in the airways. These infections can persist long-term despite being treated with high doses antibiotics. Polymicrobial infections of the airways are common in asthmatics and people with chronic obstructive or pulmonary disorder (COPD).

The genetic code of the human genome can be viewed. Pseudomonas The researchers were able identify specific mutations that lead to antibiotic resistance by analyzing bacteria in the lab-grown mixture. These mutations occurred more often when other pathogens were present.

Comparison with the genetic codes of 800 samples Pseudomonas These mutations were also discovered in human patients who had been infected by the virus. PseudomonasColistin is used to treat them.

“The problem is that once you use an antibiotic to treat any microbial infection, the microbes will develop resistance to that antibiotic. Since colistin was introduced in the early 1990’s, this has been what has happened. This is yet more evidence of the need to find new anti-infectives to treat human infections,” said Welch.

Source:

Journal reference:

O’Brien, T.J., et.(2022). Decreased effectiveness of antimicrobial agent in a polymicrobial milieu. The ISME Journal. doi.org/10.1038/s41396-022-01218-7.

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