When other germs are present, substantially greater dosages of antibiotics are required to clear a bacterial infection of the airways, according to a study.
The study explains why, despite treatment, respiratory infections are common in persons with lung illnesses like cystic fibrosis.
Researchers maintain that even a low quantity of one type of microbe in the airways can have a significant impact on how other microorganisms respond to antibiotics, according to the study, which was published today in The ISME Journal. The findings underscore the need of taking into account the interactions between different microbe species when treating illnesses with antibiotics, and adjusting dosage accordingly.
“People with chronic infections often have co-infection with several pathogens, but the problem is we don’t take that into account in deciding how much of a particular antibiotic to treat them with. Our results might help explain why, in these people, the antibiotics just don’t work as well as they should,“ said Thomas O’Brien who carried out the research and is joint first author of the paper.
Antibiotics have a hard time curing chronic bacterial infections like those in the human respiratory system. Despite the fact that these infections are commonly linked with a particular pathogenic species, the infection location is often colonized by a variety of different microorganisms, the majority of which are not harmful.
The majority of treatment methods focus on eradicating the disease, with little regard for the co-existing species. However, these treatments are frequently ineffective in wiping out the illness. Scientists have had little insight into why this is the case until today.
To achieve their findings, the researchers shaped a simplified model of the human airways that incorporated artificial sputum (‘phlegm’) that was chemically modified to match the real phlegm coughed up during an infection and was filled with germs. They were able to grow a variety of micro-organisms, including pathogens, in a stable manner for weeks at a time using the model. This is unusual because, in most cases, one virus quickly outgrows the others, causing the experiment to fail. It allowed the researchers to duplicate and investigate infections caused by numerous species of microbes in the lab, which are known as ‘poly-microbial infections.’
The bacteria Pseudomonas aeruginosa and Staphylococcus aureus, as well as the fungus Candida albicans, were employed in the experiment, which is a frequent mix in the airways of persons with cystic fibrosis. The researchers used Colistin, an antibiotic that is particularly efficient against Pseudomonas aeruginosa, to treat this microbial combination. The antibiotic didn’t work when other infections were present alongside Pseudomonas aeruginosa.
“We were surprised to find that an antibiotic that we know should clear an infection of Pseudomonas effectively just didn’t work in our lab model when other bugs were present,” said Wendy Figueroa-Chavez, joint first author of the paper.
When the microbial mix was treated with Fusidic acid, an antibiotic that targets Staphylococcus aureus, and Fluconazole, an antibiotic that targets Candida albicans, the same effect occurred. Whenever bacterium was part of a polymicrobial infection, the researchers discovered that much larger doses of each antibiotic were required to kill bacteria than when no other pathogens were present.
“All three species-specific antibiotics were less effective against their target when three pathogens were present together,” said Martin Welch, the senior author of the paper.
Antibiotics are currently mainly tested in the lab against the infection they are designed to combat in order to find the lowest effective dose. However, when the same dose is used to treat an infection in a person, it frequently fails, and this study sheds light on why. The new model system will allow researchers to evaluate the efficacy of prospective new medicines against a variety of micro-organism species.
Polymicrobial infections are common in cystic fibrosis patients’ airways. Despite receiving high doses of antibiotics, these infections can remain for a long time. Polymicrobial infections of the airways are common in persons with asthma and chronic obstructive pulmonary disease (COPD).
The researchers were able to detect particular mutations that cause antibiotic resistance by looking at the genetic code of the Pseudomonas bacteria in their lab-grown mix. When other infections were present, the mutations were observed to occur more frequently. These alterations have also been found in human patients who have been infected with Pseudomonas and treated with Colistin, according to a comparison of the genetic code of 800 samples of Pseudomonas from throughout the world.
“The problem is that as soon as you use an antibiotic to treat a microbial infection, the microbe will start to evolve resistance to that antibiotic. That’s what has happened since Colistin started to be used in the early 1990’s. This is another reminder of the vital need to find new antibiotics to treat human infections,” said Welch.
Parvathy Sukumaran 
