Higher doses of antibiotics are needed to eliminate infections in a multimicrobial environment

One study found that much higher doses of antibiotics were needed to eliminate bacterial infections of the respiratory tract in the presence of other microorganisms. Despite treatment, it helps explain why respiratory infections often persist in people with lung diseases such as cystic fibrosis.

Published today in research ISME JournalResearchers say that even low levels of certain types of microorganisms in the airways can have a significant impact on how other microorganisms respond to antibiotics.

The results highlight the need to consider interactions between different species of microorganisms and adjust doses accordingly when treating antibiotic infections.

“People with chronic infections often co-infect with some pathogens, but the problem is that they do not take that into account when determining the amount of specific antibiotics to treat them. Our results May help explain the reasons for these people. Antibiotics do not work as expected, “said a doctoral degree study at the Department of Biochemistry at Cambridge University and co-lead author of this paper. Thomas O’Brien said.

Chronic bacterial infections, such as those found in the human respiratory tract, are very difficult to treat with antibiotics. Although these types of infections are often associated with a single pathogenic species, the site of infection is often co-colonized by many other microorganisms, most of which are usually by themselves. Not pathogenic.

Treatment options usually revolve around targeting pathogens, with little consideration for coexisting species. However, these treatments often do not resolve the infection. So far, scientists have little insight into why this is.

To get their results, the team has developed a simplified model of the human airway. It contains artificial sputum (“sputum”) designed to chemically resemble real sputum that coughed during infection and is clogged with bacteria.

This model allowed a mixture of various microorganisms, including pathogens, to grow in a stable manner for several weeks at a time. This is novel because one pathogen usually grows faster than the other and ruins the experiment. This allowed researchers to recreate and study infectious diseases caused by multiple microbial species called “multimicrobial infections” in the laboratory.

The three microorganisms used in the experiment were bacteria Pseudomonas aeruginosa When Staphylococcus aureus, And fungi Candida albicans – A combination commonly present in the airways of people with cystic fibrosis.

Researchers treated this microbial mixture with an antibiotic called colistin. This is very effective in killing. Pseudomonas aeruginosa. But when other pathogens are present together Pseudomonas aeruginosa, Antibiotics didn’t work.

The antibiotics we know Pseudomonas In the presence of other bugs, it didn’t really work in the lab model. “

Wendy Figueroa-Chavez, Department of Biochemistry, University of Cambridge, Co-lead author of the treatise

The same effect occurred when the microbial mixture was treated with fusidic acid, a specifically targeted antibiotic. Staphylococcus aureus, And with fluconazole- Antibiotics specifically targeted Candida albicans.

Researchers have found that significantly higher doses of each antibiotic are needed to kill the bacteria when the bacteria are part of a multimicrobial infection compared to the absence of other pathogens. did.

Martin Welch, a professor of microbial physiology and metabolism at the University of Cambridge’s Department of Biochemistry and senior author of the treatise, said:

Currently, antibiotics are usually tested only in the laboratory against the major pathogens they are designed to target in order to determine the lowest effective dose. However, treating human infections with the same dose is often ineffective. This study will help explain why. The new model system makes it possible to test the efficacy of potential new antibiotics together against a mixture of microbial species.

Multimicrobial infections are common in the respiratory tract of people with cystic fibrosis. Despite treatment with powerful antibiotics, these infections often persist for long periods of time. Chronic infections of the respiratory tract in people with asthma and chronic obstructive pulmonary disease (COPD) are also often multimicrobial.

By looking at the genetic code of Pseudomonas Bacteria in a laboratory-grown mixture were able to identify specific mutations that cause this antibiotic resistance. Mutations were found to occur more frequently in the presence of other pathogens.

Comparison with 800 samples of genetic code Pseudomonas From all over the world, it has become clear that these mutations are also occurring in infected human patients. Pseudomonas Treated with colistin.

“The problem is that as soon as an antibiotic is used to treat a microbial infection, the microorganism begins to evolve resistance to that antibiotic, which has happened since colistin began to be used in the early 1990s. It is imperative to find new antibiotics to treat human infections, “Welch said.