Daniels TW, Rogers GB, Stressmann FA, van der Gast CJ, Bruce KD, Jones GR, Connett GJ, Legg JP, Carroll MP Marsh P, Vermeer LS, Hoffman L, Patel N, Forbes B
Place of research
Southampton University Hospitals NHS Trust & King's College London, UK
Journal of Cystic Fibrosis, January 2013 & Thorax October 2012
What happens to bacteria when patients receive intravenous antibiotics for pulmonary exacerbations?
Are bacteria that haven’t previously been recognised as causing infection in CF present over long periods, comparable to CF-related species, such as Pseudomonas aeruginosa?
Why is this important?
Bacterial infections are of primary importance in determining the respiratory health of patients with CF. The introduction of antibiotic therapy has greatly improved patient longevity and quality of life. However, different antibiotics have varying levels of effectiveness against particular bacterial species. To select antibiotics appropriately, it is important to know which bacterial species are contributing to a worsening of symptoms.
What did you do?
Traditionally, sputum samples have been analysed by growing bacteria on agar plates in the laboratory. However, we now know that many types of bacteria grow very poorly under these conditions, and may go undetected. New techniques have been developed that avoid the need for culture and instead detect bacteria based on DNA, extracted directly from sputum samples. Applying this type of analysis to CF sputum has revealed the presence of many previously undetected bacterial species.
To answer the research questions, a technique called T-RFLP profiling was used to obtain an overview of the bacterial content of samples. In the first study, samples were analysed prior to, during, and after IV antibiotic therapy; in the second, analysis was performed on samples collected from patients every month over a year.
What did you find?
We found that patients had unique combinations of bacteria in their lungs. During treatment for exacerbations, levels of these species tended to fall relative to levels of P. aeruginosa. This finding may reflect the natural resistance of P. aeruginosa to antibiotics, being able to survive when the levels of other species are reduced. However, when we looked at the bacterial communities over the year, we found that they were relatively stable, with species profiles recovering following periods of therapy; the newly detected species showing similar levels of resilience to those recognised traditionally. These findings suggest that the novel species represent chronic infections, arguably comparable to species more usually associated with CF.
What does this mean and reasons for caution?
In both studies, we found that low numbers of bacterial species in the airways was associated with poor respiratory health. This relationship, confirmed in other studies, may reflect the fact that as airway disease gets worse, patients tend to receive antibiotics more frequently, gradually removing the more susceptible species from their airways over time.
Studies are now required to assess the contribution of each bacterial species detected to CF lung disease using these new techniques, and to determine whether modifications to therapy are necessary now that we know they are there.