Why does CF differ from other diseases of AMR?
The common pulmonary pathogens in CF are Pseudomonas aeruginosa (chronic and intermittent), Burkholderia cepacia complex, non-tuberculosis mycobacteria such as Mycobacteria abscessus, as well as Aspergillus. In children, Staphylococcus aureus is also a problem.
CF differs from other diseases of AMR for a number of reasons including:
- the lung flora evolves over a long time and microbial strains adapt to their environment
- CF bacteria form biofilms in the lung, which together with the thick mucus from the lung make antimicrobial penetration very difficult
- two disease states exist: chronic and acute (with periodic flare ups/exacerbations), and both require different treatment strategies
- the adaptation of microbes to the unique host environment creates a disconnect between antimicrobial susceptibility testing (data produced in the lab) and clinical outcomes (what is seen in patients) – necessitating the use of clinical strains for antimicrobial development
Why does CF represent a useful disease model for other conditions?
The CF academic community have an extensive understanding of the pathophysiology of pulmonary infections in CF and have developed key assets and knowledge that can help drive through discovery in this space.
CF is an ideal exemplar for other respiratory conditions, with a data rich, longitudinal patient registry hosted by the Cystic Fibrosis Trust. In addition, the Cystic Fibrosis Trust has invested in the research of these academics and has also worked with the biotechnology sector to enable investments in the latest cutting-edge genomics and analytical technologies designed to identify key intervention points, as well as investments in understanding the development of resistance and virulence.
CF also benefits from the Clinical Trials Accelerator Platform; a UK-wide network of trial coordinators with the remit to promote access to and speed up the process of clinical trials, which has been set up by the Cystic Fibrosis Trust. This provides the ideal platform to rapidly test the effectiveness of new antimicrobials in people affected by CF.
How does the CF Syndicate in AMR complement existing initiatives?
The CF Syndicate in AMR will complement existing worldwide initiatives in this area. For example, the “Antimicrobial Resistance International Working Group in Cystic Fibrosis” established by the European Cystic Fibrosis Society, recommended in their recent peer reviewed publication that:
“…research priorities should include the establishment of improved diagnostic assays that directly detect AMR in bacteria within their microbial communities and test the efficacy of antibiotics within the conditions of the CF airway.”
The CF Syndicate in AMR will address this recommendation by driving collaborative programmes in the areas of focus identified.
Although the CF Syndicate in AMR’s research agenda is focussed, we will seek to identify areas of alignment with other international initiatives and identify opportunities to collaborate to drive faster progress.
Other relevant initiatives include:
- Biotech companies in Europe combating antimicrobial resistance (BEAM Alliance)
- Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X)
- Joint Programming Initiative on Antimicrobial Resistance (JPIAMR)
- the Cystic Fibrosis Foundation’s Infection Research Initiative
- the Cystic Fibrosis Trust and University of Cambridge Innovation Hub for Lung Health
- the National Biofilm Innovation Centre (NBIC)