Antibiotics to treat cystic fibrosis are not as effective when a mixture of microbes are present


According to a new study, antibiotics are less effective in treating lung infections in cystic fibrosis (CF) when there are multiple types of infecting microorganisms.

“People with chronic infections are often co-infected with multiple pathogens, but the problem is that we don’t take that into account when deciding how much of a particular antibiotic to treat them with. Our findings could help explain why, in these people, antibiotics just don’t work as well as they should,” Thomas O’Brien, the study’s co-first author, said in a statement. Press release. O’Brien did research for his doctorate at the University of Cambridge.

The study, “Decreased efficacy of antimicrobial agents in a polymicrobial environmentwas published in The ISME magazine.

Cystic fibrosis is characterized by the buildup of thick, sticky mucus in the lungs and other organs. Mucus provides a comfortable haven for pathogenic microorganisms, and chronic lung infections are a common health problem in people with cystic fibrosis. Some of the microbes implicated in CF lung infections include Pseudomonas aeruginosa and Staphylococcus aureuswhich are both bacteria, and candida albicans, a fungus.

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It is not uncommon for a person to be infected with more than one of these agents simultaneously and microbiological research has shown that when these organisms grow together in a community they can affect the disease-related behavior of the ‘other.

“It therefore seems very likely that inter-species interactions may also alter the response of pathogens. [disease-causing agents] …to antimicrobial agents,” the researchers wrote.

Despite this likely link, “traditional antimicrobial susceptibility testing does not take into account the presence of cohabiting species, or how these microorganisms might affect the acquisition of antibiotic resistance.”

To study how the presence of other microbes affects the response to treatment of individual pathogens, researchers tested three antimicrobial drugs: colistin, which targets Pseudomonas aeruginosafusidic acid, which targets Staphylococcus aureus; and fluconazole, which targets Candida albicans.

The microbes were cultured, separately or together, in a dynamic artificial sputum model that the researchers had developed and described in detail in a study 2019. The model is intended to mimic coughed up phlegm during an infection.

“This method of modeling the airways using artificial sputum, containing a mixture of insects, may provide a new way to test the efficacy of new antimicrobial drugs,” Paula Sommer, PhD, said in a statement. . separate version. Sommer is director of research at Cystic Fibrosis Trustwho helped fund this study.

Early tests using the separately cultured bacteria showed that all agents tested worked in a species-specific manner, as expected. For example, colistin potently reduced Pseudomonas numbers, but had little effect on the other two microbes.

Comparisons of microbes cultured alone or in combination showed that antimicrobial drugs were significantly less potent against pathogens cultured in combination.

For example, when Pseudomonas bacteria were cultured alone, colistin treatment reduced their numbers about 10,000-fold within three hours of treatment. However, when the bacteria were cultured in the presence of Staphylococcus and candidiasisthe same treatment reduced Pseudomonas numbers by only about a hundredfold.

“We show a marked decrease in the efficacy of three clinically used species-specific antimicrobial compounds (colistin, fusidic acid, and fluconazole) against their target microorganism when that microorganism is cultured in a consortium. polymicrobial at steady state. This observation underscores the need to examine how cohabiting species might alter the response of a primary pathogen to a previously validated therapeutic intervention,” the researchers concluded.

They said the finding could explain why some antimicrobial treatments fail to eliminate infections in cystic fibrosis, even though the treatment can easily kill the bacteria in lab tests.

Experiments have also indicated that treatment resistance involves both physiological and adaptive elements – in other words, some microbes retain treatment resistance even after other cohabiting microbes have been eliminated, but in other cases , elimination of other microbes also suppressed treatment resistance. In Pseudomonas bacteria that remained resistant, the researchers identified some specific genetic changes that likely contributed to treatment resistance.

“The problem is that as soon as you use an antibiotic to treat a microbial infection, the microbe begins to develop resistance to that antibiotic. This has been happening since colistin began to be used in the early 1990s. This is another reminder of the vital need to find new antibiotics to treat human infections,” said Martin Welch, PhD, Cambridge professor and lead author of the study.


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