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Growing a Cystic Fibrosis-Relevant Polymicrobial Biofilm to Probe Community Phenotypes
Published on: April 19, 2024
Cystic fibrosis infections: treatment strategies and prospects
Anthony M George1, Peter M Jones, Peter G Middleton
1Institute for the Biotechnology of Infectious Diseases, University of Technology Sydney, Broadway, NSW 2007, Australia. tony.george@uts.edu.au
Abstract:
Pseudomonas aeruginosa and Burkholderia cepacia are the two major Gram-negative rods that colonize/infect the lungs of patients with cystic fibrosis (CF). These organisms may cause progressive respiratory failure, although occasionally more rapid infections result in the 'Cepacia' syndrome. Many antibiotics have been used against Pseudomonas and Burkholderia, but once chronic colonization has been established, eradication of these organisms is rare. Drug therapy for CF patients is compromised by a number of bacterial factors that render the infectious agents resistant to antibiotics, including efflux pumps that remove antibiotics, lack of penetration of antibiotics into bacterial biofilms, and changes in the cell envelope that reduce the permeability of antibiotics. Any combination of these mechanisms increases the likelihood of bacterial survival. Therefore, combinations of antibiotics or of antibiotic and nonantibiotic compounds are currently being tested against Pseudomonas and Burkholderia. However, progress has been slow, with only occasional combinations showing promise for the eradication of persistent Gram-negative rods in the airways of CF patients. This review will summarize the current knowledge of CF infections and speculate on potential future pathways to treat these chronic infections.
Insights
Treating chronic lung infections in cystic fibrosis (CF) patients with Pseudomonas aeruginosa and Burkholderia cepacia is challenging due to bacterial resistance mechanisms. New combination therapies show limited promise for eradicating these persistent Gram-negative rods.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Pulmonology
Background:
- Cystic Fibrosis (CF) patients frequently suffer lung colonization by Pseudomonas aeruginosa and Burkholderia cepacia.
- These Gram-negative rods can lead to progressive respiratory failure and 'Cepacia' syndrome.
- Eradicating chronic colonization of these bacteria in CF airways is rarely achieved with current antibiotic therapies.
Purpose of the Study:
- To review current knowledge on Pseudomonas and Burkholderia infections in cystic fibrosis.
- To explore bacterial resistance mechanisms hindering effective drug therapy.
- To discuss potential future treatment strategies for chronic Gram-negative rod infections in CF patients.
Main Methods:
- Literature review of existing studies on CF lung infections.
- Analysis of bacterial factors contributing to antibiotic resistance.
- Examination of current and emerging combination therapies.
Main Results:
- Bacterial resistance mechanisms, including efflux pumps, biofilm penetration issues, and reduced antibiotic permeability, significantly compromise drug efficacy.
- Combinations of antibiotics or antibiotic and nonantibiotic compounds are under investigation.
- Progress in developing effective eradication strategies has been slow, with few combinations showing significant promise.
Conclusions:
- Persistent Gram-negative rod infections in CF airways remain a major clinical challenge.
- Novel therapeutic approaches are urgently needed to overcome established resistance mechanisms.
- Further research into combination therapies is crucial for improving treatment outcomes in cystic fibrosis patients.
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