As mentioned before patients with cystic fibrosis (CF) have a build-up of sticky
mucus in the lungs, pancreas and other organs.1 This mucus clogs the
airways and traps bacteria, leading to infections, extensive lung damage and
respiratory failure.1 One of the treatment options for patients with
cystic fibrosis is the use of inhaled antibiotics. However, just as the disease
itself causes the airway microbiome to change, so could the use of antibiotics.
Whether this is desirable is a question that can only be answered by
researching the microbiome of CF patients after antibiotic treatment.
Benefits of understanding the airway microbiome
Understanding the airway microbiome of CF
patients can not only help identify the patients that will respond better to
certain treatments, but it can also help prevent resistance to antimicrobial
therapy. Antimicrobial resistance is seen in CF patients due to the extensive
use of antimicrobial treatments from a young age.4 This increase in
antimicrobial resistance in CF patients leads to a need for new strategies for
the lifelong treatment of pulmonary infections.4 The approach that
is currently being researched is the use of personalized antibiotic therapy. This
would be based on microbiological analyses of the airway microbiome for every individual. This is important since we are facing a post-antibiotic
era with limited capability to combat polymocrobial infections.4
Figure
1 Author unknown. Antibiotics and CF.5
Effect of antibiotics on the airway microbiota
As mentioned earlier, the airway microbiome in healthy individual is composed of several bacteria such as Streptococcus, Prevotella, Fusobacteria, and Veillonella, with lesser contributions by Haemophilus and Neisseria6. However, the airway microbiome of CF patients consists of bacterial pathogens including Staphylococcus aureus and opportunists such as Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter species, and Stenotrophomonas maltophilia2. In CF patients, an infection of P.aeruginosa is seen most frequently; 60-80% of CF patients will become chronically infected with this bacterium3. This dysbiosis of the airway microbiome could be the cause of the infections occurring in CF patients. Respiratory tract infections in CF patients are treated with inhaled antibiotics. One example is the antibiotic ‘Aztreonam lysine for inhalation solution’ (AZLI), which is used in CF patients with chronic P.aeruginosa lung infections. AZLI is found to improve lung function and quality of life, but also to reduce exacerbations. As AZLI is inhaled by nebulization into the lower airways, the question remains whether this antibiotic could also have an effect on other organisms of the airway microbiota. One of the few recent studies that assesses these questions is the study by Heirali3. In this study, patients with chronic P.aeruginosa infection were researched to determine whether a difference in airway microbiota is seen after AZLI treatment and whether these findings could be used to predict treatment responsiveness.
As mentioned earlier, the airway microbiome in healthy individual is composed of several bacteria such as Streptococcus, Prevotella, Fusobacteria, and Veillonella, with lesser contributions by Haemophilus and Neisseria6. However, the airway microbiome of CF patients consists of bacterial pathogens including Staphylococcus aureus and opportunists such as Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter species, and Stenotrophomonas maltophilia2. In CF patients, an infection of P.aeruginosa is seen most frequently; 60-80% of CF patients will become chronically infected with this bacterium3. This dysbiosis of the airway microbiome could be the cause of the infections occurring in CF patients. Respiratory tract infections in CF patients are treated with inhaled antibiotics. One example is the antibiotic ‘Aztreonam lysine for inhalation solution’ (AZLI), which is used in CF patients with chronic P.aeruginosa lung infections. AZLI is found to improve lung function and quality of life, but also to reduce exacerbations. As AZLI is inhaled by nebulization into the lower airways, the question remains whether this antibiotic could also have an effect on other organisms of the airway microbiota. One of the few recent studies that assesses these questions is the study by Heirali3. In this study, patients with chronic P.aeruginosa infection were researched to determine whether a difference in airway microbiota is seen after AZLI treatment and whether these findings could be used to predict treatment responsiveness.
The study3 looked at sputum
samples of twenty-four CF patients before and after treatment with AZLI. The DNA
of the sputum samples were then analysed with PCR. Taxonomic summaries were
used to identify the microbial changes after the initiation of AZLI. It
appeared that while some patients airway microbiota was dominated by
Pseudomonas, others were more diverse. The study showed that there were no
differences in alpha or beta diversity correlating to the AZLI treatment. However,
in post-AZLI samples a significantly lower relative abundance in Prevotella and higher relative abundance
of Granulicatella was observed. The study
next investigated whether microbiome changes may be used as a biomarker to
identify patients more or less likely to respond to AZLI treatment. It was
found that AZLI non-responders had a lower abundance of Pseudomonas and a higher abundance of Staphylococcus, Fusobacterium, and Prevotella. Higher abundances of Fusobacterium and Bacteroides
following treatment initiation were also associated with a lack of clinical
response.
Relevance of airway microbiome research
Relevance of airway microbiome research
This study shows that research in the field
of airway microbiota and antibiotics is important for it cannot only benefit
personalisation of treatment in patients with CF, but it can also help fight the
battle against antimicrobial resistance in the long run. Therefore, in my
opinion, there should be more research done in order to comprehend the airway
microbiota and the consequences of its dysbiosis.
Written by Malak Al-Gawahiri
References:
1.
Author unknown. About Cystic
Fibrosis: What Is Cystic Fibrosis? Cystic fibrosis foundation. Available on: https://www.cff.org/What-is-CF/About-Cystic-Fibrosis/
Last seen on Oct. 14th 2017.
2. James F. Chmiel et al. Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections. Ann Am Thorac Soc. 2014 Sep; 11(7): 1120–1129. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467101/.
3. Heirali AA. The effects of inhaled aztreonam on the cystic fibrosis lung microbiome. Microbiome. 2017 May 5;5(1):51. Available on: https://www.ncbi.nlm.nih.gov/pubmed/28476135 .
2. James F. Chmiel et al. Antibiotic Management of Lung Infections in Cystic Fibrosis. I. The Microbiome, Methicillin-Resistant Staphylococcus aureus, Gram-Negative Bacteria, and Multiple Infections. Ann Am Thorac Soc. 2014 Sep; 11(7): 1120–1129. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467101/.
3. Heirali AA. The effects of inhaled aztreonam on the cystic fibrosis lung microbiome. Microbiome. 2017 May 5;5(1):51. Available on: https://www.ncbi.nlm.nih.gov/pubmed/28476135 .
4.
Magalhães AP et al. The cystic
fibrosis microbiome in an ecological perspective and its impact in antibiotic
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.
5.
Author unknown. Cause Behind
Cystic Fibrosis’ Progression Found. Atlanta ENT. Available at: https://www.atlantaent.com/cause-behind-cystic-fibrosis-progression-found/
. Last seen on Oct. 15th 2017.
6.
Beck JM. ABCs of the Lung
Microbiome. Ann Am Thorac Soc. 2014 Jan; 11(Suppl 1): S3–S6. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972977/
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