Antibiotic-resistant bacteria are more common than expected among people with cystic fibrosis

Therapy Breakthroughs 19. jul 2021 3 min Chief physician, Professor, DMSc Helle Krogh Johansen Written by Morten Busch

People with cystic fibrosis are constantly battling bacterial respiratory infections. In the past, the reason why people often ended up being infected with the same bacterium was mysterious. A new study now reveals that specially adapted bacteria pose an increased risk of transmission to other people and of developing antimicrobial resistance.

The treatment of people with cystic fibrosis has been revolutionized in recent years, with treatment specifically targeting the cystic fibrosis-transmembrane regulator protein which stabilise or improve the lung function of most people with cystic fibrosis. Although there are grounds for optimism, new results are now causing researchers to raise a red flag. The reason is that new and more precise methods for genetically analysing specific bacteria show that bacterial infections that can threaten these people’s lives are different from what was thought just a few years ago.

“Our new study shows that the most common method of bacterial identification is simply not precise enough. Although the method shows that these people are infected with Achromobacter, many people have a different species than previously thought. We also found that the number of people with cystic fibrosis infecting each other is higher than we had expected. Since the bacterium also has a much greater tendency to mutate and become resistant, identifying the exact species of Achromobacter is important so that people do not infect each other,” explains Helle Krogh Johansen, Clinical Professor, Department of Clinical Microbiology, Rigshospitalet, Copenhagen and Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby.

Only half correctly determined

Cystic fibrosis is one of the most common inherited, single-gene disorders. People with cystic fibrosis produce thick and sticky mucus, creating an ideal growth environment for bacteria in the lungs. Most of these people have persistent bacterial respiratory infections, which often cause respiratory failure and premature death. Pseudomonas aeruginosa is the most common bacterium in the lungs of people with cystic fibrosis, but another one now appears to be on the increase.

“As we have increasingly improved treating people with Pseudomonas aeruginosa lung infections and the technology to differentiate bacteria has greatly improved, we realized that more and more people with cystic fibrosis are being infected with other bacteria in their lungs, including Achromobacter species. One major challenge of Achromobacter species is that they often develop antibiotic resistance, and this leads to a more serious disease trajectory. Since there was relatively little knowledge on Achromobacter infections, the aim of the new study was to identify the extent of the problem,” says Helle Krogh Johansen.

In addition to creating an overview, the researchers wanted to test existing clinical diagnostics based on mass spectrometry, which examines the protein pattern in the bacteria. The researchers performed whole-genome sequencing for bacterial identification, and this more accurate method yielded several surprises.

“We sequenced the genomes of 101 Achromobacter clinical isolates previously identified as Achromobacter xylosoxidans collected from 51 people with cystic fibrosis from 1996 to 2018. However, the genome sequences showed that only 52% of the infections were caused by Achromobacter xylosoxidans. The remaining 48% included five Achromobacter species, and the most worrying was that 25% turned out to be Achromobacter ruhlandii – a species that often mutates, leading to antimicrobial resistance and has the potential for person-to-person transmission,” explains Helle Krogh Johansen.

Changes required despite the revolution

Being aware of the person-to-person transmission of cystic fibrosis infections is important. Frequent hospital outpatient check-ups increase people’s risk of bacterial infection and increase the risk of people with cystic fibrosis infecting each other. Today, these people are monitored in two specialized wards in Aarhus and Copenhagen with excellent infection hygiene involving a very extensive regimen to minimize the risk of transmission. In addition, the relationship between patients’ lung bacteria is examined regularly to detect and prevent person-to-person transmission.

“Although most of the people studied harboured unique Achromobacter clone types, our suspicion of transmission between patients was confirmed in more than one third of the cases because they had the same clone types and because the hospital visits were associated with the genetic profile of the bacteria. Achromobacter ruhlandii has proven to be especially contagious,” says Helle Krogh Johansen.

It is still too early to say how the recent revolution in modulator treatment of people with cystic fibrosis will affect lung infections. The modulators compensate for the genetic mutation these people have in the cells’ chloride channels, which creates a fluid deficiency in the mucus in the body. Although this treatment apparently makes the mucus waterier and stops the fibrosis and thus the breakdown of the tissue, whether this completely solves the infection problem is still unknown.

“So far, evidence indicates that the infections subside for a while, but if the supportive modulator treatment is not continued, the bacteria return, so for now we must assume that we have to keep fighting the infection. Our new results show that new genetic methods for identifying the bacteria from people with cystic fibrosis are a necessary supplement to the methods used today, since these are not sufficiently precise. Continuing to isolate the people with the most contagious and antibiotic-resistant types of bacteria is also important,” concludes Helle Krogh Johansen.

Transmission and antibiotic resistance of achromobacter in cystic fibrosis” has been published in the Journal of Clinical Microbiology. In 2019, the Novo Nordisk Foundation awarded a Challenge Programme grant to Helle Krogh Johansen for the project Persistent Bacterial Infections (PERFECTION).

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