Current research

ANTIMICROBIAL RESISTANCE IN CYSTIC FIBROSIS

International Task force

The prevalence of antimicrobial resistance (AMR) among microbial pathogens is increasing and is a high priority worldwide for interventions from antibiotic stewardship to new antibiotic development (http://www.who.int/antimicrobial-resistance/en/).  Increasing AMR prevalence is driven by the widespread use of antibiotics.

AMR is commonly encountered in bacteria and fungi isolated from the airways of people with cystic fibrosis (CF).  This is an expected finding given the high use of antibiotics in CF patients. The increasing survival of people with CF will result in greater lifetime exposure to antibiotics.

There is a lack of full understanding for stakeholders including people with CF, clinicians, the pharmaceutical industry, and (drug approving) regulatory bodies, about the relevance of AMR and how this should influence drug development and usage in the treatment of CF lung disease.

The Taskforce will develop guidelines on the interpretation of AMR for clinical care in CF. The Taskforce will also provide guidance on the role of AMR in clinical trials with new antimicrobial agents. The Taskforce that will have international and multidisciplinary representation will address the following objectives:

  • Understand how chronic infections differ from acute infections with respect to the microbiological assumptions regarding AMR.
  • Describe current and developing methodologies for determining antimicrobial resistance.
  • Assess the value of current susceptibility testing including the frequency and timing of testing.
  • Offer guidance for the use of antimicrobial resistance testing in the conduct of clinical trials by the pharmaceutical industry and regulatory agencies.
  • Set key research priorities for the development of appropriate future application of AMR diagnostics to improve patient outcomes.
  • Explore how monitoring antibiotic usage impacts on AMR in people with CF.

Australia/New Zealand Representatives

  • Cass Byrnes, CF pediatrician
  • Jason Roberts, pharmacist
  • Tim Kidd, microbiologist
  • Scott Bell, adult CF physician

ACFRT award Innovation Grant

Dr Jay Horvat will work with Professors Phil Hansbro and Professor Peter Wark on a new investigation exploring the role and therapeutic targeting of iron in Cystic Fibrosis thanks to a new grant from the Australian Cystic Fibrosis Research Trust.

This Innovation Award will enable Jay and his team to explore initial novel concepts into Cystic Fibrosis (CF) over the next year.

Cystic Fibrosis is a life-limiting genetic disease characterised by severe breathing difficulties caused by thick mucous in the airways and by frequent and chronic respiratory infections.

One in 25 Australians carry a defective gene (CFTR), and one in 3000 births results in Cystic Fibrosis.

The life expectancy of people with CF is around 38 years, with the respiratory failure due to bronchiectasis the leading cause of death.

Healthcare costs are high, with associated personal and social costs from impaired quality of life impacting on both people living with CF and their families. 

While there have been improvements in management or treatment of CF, more effective therapies are urgently required for infections such as Pseudomonas. 

The role of iron levels in people with CF is an area that the team are looking to explore as high iron levels in the lung lead to increased susceptibility to infection with Pseudomonas and subsequent disease progression and pulmonary exacerbations in CF.

An increased understanding of the role that increased iron levels in the lung play in CF may identify iron as a biomarker for CF exacerbations and could lead to improved therapies for the prevention or management of the disease.

The Australian Cystic Fibrosis Research Trust bestows the annual Innovation Award, to allow CF researchers to explore novel concepts at the initial feasibility stage, with the aim of generating sufficient data to continue the research after the preliminary 12-month-period.

Jay intends on using the data collected from the study to be used to generate grant applications for submission to research funding bodies to fund a large translational study that will investigate the interplay between iron and infection in Cystic Fibrosis.

The grant was evaluated by both a TSANZ committee and a CF consumer group and awarded at the TSANZ AGM which took place on Saturday 25th March at 5pm at the TSANZSRS Annual Scientific Meeting (ASM) in Canberra.

 

 ‘Multi-action antibiotics to treat chronic biofilm infections’

Cystic Fibrosis Australia announced that the Trustees for the  Australian Cystic Fibrosis Research Trust (ACFRT) approved funding of an important research study coming out of the University of Wollongong, with Nanyang Technological University as the conferring institution.

Chief Investigator  -  Associate Professor Michael Kelso in conjunction with
Associate Professor Scott Rice

Project title – ‘Multi-action antibiotics to treat chronic biofilm infections’

The ACFRT have committed to fund the project to $588,687 over 3 years and we are pleased to provide the most recent update on the project.  

The project was Peer Reviewed to ‘Worlds Best Practice’ by the NHMRC review process.

Thanks are extended to the NHMRC for their cooperation in providing to ACFRT recommendations for funding. CFA offers congratulations to Associate Professor Michael Kelso and his team and we wish them well with the progress and outcomes of this important project for the Cystic Fibrosis community.

Thanks are also extended to the many supporters and donors to ACFRT without whom such valuable research would not be funded. 

Further enquiry can be directed to Cystic Fibrosis Australia on 02 9889 5171 or via general@cfa.org.au

 

Past research

2012 Projects Funded - $313,926

Dr M.J. Farrell, Dr S.B. Mazzone & Dr D. Smallwood

Brain responses during airway irritation and cough suppression in people with Cystic Fibrosis

Florey Neuroscience Institutes

$155,829

Dr E. Hart, A/Prof. S. Ranganathan & Prof. R.M. Robins-Brown

The role of staphylococcal infections in early cystic fibrosis lung disease.

The Murdoch Children’s Research Institute 

$83,048

Dr C.Y. Ooi, Professor A. Jaffe, A/Prof. A.S. Day & Prof. H. Mitchell

The gut-lungaxis: defining and understanding the gut microbiota in cystic Fibrosis.

The University of NSW

$75,049

 

2011 Projects Funded - $283,885

Prof. G. Jenkin, Prof. E. Wallace

Administration and engraftment of amnion stem cells for treatment of CF.

Monash Institute of Medical Research - Melbourne

$92,517

Dr DW. Parsons, Dr A. Fouras, Dr KKW. Siu, Prof. S. Hooper, Dr M. Donnelley.

Localised detection of early stage CF disease via quantitative imaging of lung motion.

Women’s and Children’s Hospital – Adelaide

$110,749

Dr DW. Reid, A/Prof. SC. Bell, A/Prof. MA Schembri, Prof. IL. Lamont.

Targeting the Achilles heel of P. aeruginosa biofilms

Queensland Institute of Medical Research – Brisbane

$80,619

 

2010 Projects Funded - $306,038

Prof. P.D. Sly, Prof. S.M. Stick, Prof. C.F. Robertson, Prof. P.J. Robinson, Prof. C.E. Wainwright, Prof. K. Grimwood, Prof. T. Sloots, Prof. M. Nissen, Dr I.A. Laing.

Viral burden in infants with cystic fibrosis

University of WA  –   Telethon Institute for Child Heath Research

$91,906 

Dr D.M. Whiley, Mr T.J. Kidd, Ms S. Anuj, A/Prof. C.T. Sloots, A/Prof. S.C. Bell, A/Prof. M.D. Nissen, Prof. K. Grimwood, A/Prof. C.E. Wainwright, Dr R. Ware.

Development of a novel assay for the detection of clonal P.aeruginosa in persons with CF.

Queensland Children’s Medical Research Institute

$68,950

A/Prof P. Bye, A/Prof A. Jaffe, A/Prof P.A.B. Wark, Dr M.R. Elkins.

Trial of nebulised 0.9% vs 6% saline for people with cystic fibrosis

Royal Prince Alfred Hospital

$95,723

Dr S. Hameed, Dr C.F. Verge, Associate Professor A. Jaffe.

CF-IDEA (Cystic fibrosis – Insulin Deficiency, Early Action.)

The Sydney Children’s Hospital

$49,459

 

2009 Projects Funded - $405,078

Dr M.A. Cooley, Dr L. Roddam, Dr D.W. Reid, A/Prof A. Jaffe

Pseudomonas infection as an indirect cause of CF Related Diabetes.

The Menzies Research Institute

$96,097

A/Prof. S. Bell, Mr T.J. Kidd, 

Prof. K. Grimwood, A/Prof. C.E. Wainwright, Prof. P.B. Rainey, Dr M. Hargreaves, A/Prof. M.D. Nissen.

Multilocus sequence typing of Pseudomonas aeruginosa from different niches.

The Prince Charles Hospital

$83,840

Dr S. Beatson, A/Prof. B. Rose, A/Prof. C.E. Wainwright, Dr J. Manos, A/Prof. C. Harbour, Dr T. Thomas, Prof. K. Grimwood.

Genomics as a tool to study P aeruginosa lung disease in cystic fibrosis”

The University of Sydney

$79,500

Dr S.G. Devadason

Optimal delivery of CF therapy from vibrating membrane (mesh) nebulisers.

The Princess Margaret Hospital

$78,025

A/Prof. P.T.P. Bye, Dr M.R. Elkins, Ms R.L. Dentice, A/Prof. J.A .Alison

The effect of physiotherapy for airway clearance in people with cystic fibrosis.

Royal Prince Alfred Hospital

$67,616

 

2008 Projects Funded -  $559,062

Prof. R. Williamson, Dr F. Zaibak.

Characterisation of cord blood-derived lung epithelial cell

The University of Melbourne

$89,355

Dr D.W. Reid, A/Prof. I.L. Lamont, Mr C.Y. O’May.

Unravelling P. aeruginosa iron acquisition mechanisms in vivo: novel insights and potential therapies

Menzies Research Institute, University of Tasmania

$87,879

Prof. P.D. Sly, Dr S. Brennan, A/Prof. A.J. Kettle, Dr M.S. Cooke, Prof. J. Grigg.

Validating 8-oxodG as a biomarker of oxidative stress in children with CF

University of Western Australia.

$84,304

Prof. S.A. Kjellberg, A/Prof. S.M. Kirov, Dr J.S. Webb, Dr T. Thomas

Geonomic approach to targeting pseudomonas aeruginosa persistence in the C F  airway

University of NSW

$80,043

A/Prof. S.M. Stick, Dr A. Kicic, Dr E.N. Sutanto.

Response of paediatric CF-derived airway epithelium to viral injury

Telethon Institute for Child Health Research

$80,000

A/Prof. J.A. Alison, A/Prof. P.B. Bye, A/Prof. S. Eberl, Prof. C.M. Mellis, Dr E.D. Daviskas.

Does exercise enhance mucus clearance in adults with cystic Fibrosis? 

University of Sydney.

$69,695

A/Prof. P. Bye, A/ Prof. S. Bell, A/ Prof. B. Rose, A/Prof. C. Harbour, A/Prof. G.B Marks, A/Prof. P.J. Robinson, Dr J. Manos.

Establishing the prevalence of clonal Pseudomonas aeruginosa strains in cystic fibrosis clinics across Australia

Royal Prince Alfred Hospital.

$67,750 

 

2007 Projects Funded - $428,637

Prof. R. Williamson, Dr F. Zaibak

The University of Melbourne

Differentiation and immunology of cord blood stem cells: Towards CF therapy.

$89,448

Dr S. Brennan, Prof. P.D. Sly, Dr T.A. Douglas, Prof. K. Grimwood, A/Prof. C.E, Wainwright

Exploring serum antibodies for the early detection of P. aeruginosa in Cystic Fibrosis.

Institute for Child Health Research

$79,367

Dr B.R. Rose, Dr C.E. Wainwright, Dr C. Whitechurch, Dr J. Manos,A/Prof. C. Harbour, A/Prof. P.T.P. Bye, Dr L. Turnbull, Dr D. Armstrong, Prof. K. Grimwood, A/Prof. M. Nissen.

P. Aeruginosa in cystic fibrosis: determinants of acquisition, virulence & persistence.

Royal Prince Alfred Hospital

$78,660

Prof. J.P. Hall, Dr R.J.H. Massie

A/Prof. M. Delatycki, Mr K. van Gool

A health economic evaluation of community-wide carrier screening for cystic fibrosis.

University of Technology, Sydney.

$58,500 

A/Prof G.A. Ramm, A/Prof P.J. Lewindon, Dr V.N. Subramaniam.

The role of MCP – 1 in Hepatic Fibrosis Associated with Cystic Fibrosis.

The Queensland Institute of Medical Research

$51,938

Dr S.C. Ranganathan, A/Prof. N. Curtis, Dr G.K. Smythe, Prof. R.M. Robbins Browne

Early detection of lung disease in cystic fibrosis: a gene expression study.

Royal Children’s Hospital Melbourne

$51,317 

Dr P.A.B. Wark, Prof. P.G. Gibson, A/Prof. B. Whitehead

The role of respiratory virus infection in CF lung disease 

The John Hunter Hospital

$19,406

 

2006 Projects Funded - $327,690

A/Prof. P.G. Middleton, Prof. D.I. Cook.

Department of Physiology Westmead Hospital / University of Sydney.

Epithelial ion transport defects in Cystic Fibrosis: Pathophysiology and treatment with citrate aerosol.

$131,500        

Dr M.B. Braithwaite, A/Prof. J.W. Wilson,A/Prof T.K.                

Kotsimbos, Dr J.P. Philip, Cr M.G. Gold.

The Alfred Hospital Melbourne

A palliative care plan for progressive, non malignant disease: Cystic Fibrosis

$44,823.00

Dr C.M. Suttle, Prof. K.J. Gaskin, Dr J.R. Allen.

Children’s Hospital Westmead/ University of Western Australia.

Vitamin A deficiency and retinal function in children with Cystic Fibrosis.

$60,061.00

A/Prof C. Harbour, Dr B.R. Rose,Dr J. Manos, Dr J. Arthur           

A/Prof. P. Bye.

Royal Prince Alfred Hospital/ University of Sydney

Sequencing of transmissible Pseudomonas aeruginosa from patients with Cystic Fibrosis.  

$78,700.00

Dr D.W. Reid, Dr L. Blizzard, Ms D. Shugg, Dr H. Greville.

University of Tasmania, Menzies Centre for Population Research

Cystic Fibrosis mortality in Australia between 1979 – 2004 

The changing demographic disease.

$12,606.00 

 

2005 Projects Funded - $196,322

Dr B.R. Rose, Dr C. Wainwright, Dr J. Manos, A/Prof P.T.P. Bye,

A/Prof.S.Bell, A/Prof C. Harbour, Dr M. Nissen, Dr T. Sloots, Dr C. Coulter

Royal Prince Alfred Hospital – carried out at the Department of Infectious Diseas and 

Immunology University of Sydney, Sydney & Sir Albert Sakzewski Research Centre

Royal Children’s Hospital, Herston

Transmission of Pseudomonas aeruginosa: clinical and molecular studies                                                                 

 $74,754

A/Prof S.M. Sawyer

Murdoch Children’s Research Institute – carried out at the Department of Respiratory Medicine, Royal Children’s Hospital, Melbourne

Australian CF sexual and reproductive health (SRH) survey

$23,745

Dr H.C. Selvadurai, Dr M. Sherwood, A/Prof P.P. Van Asperen, Dr H.E. Montgomery

The Children’s Hospital at Westmead – carried out at Department of Respiratory Medicine, The Children’s Hospital at Westmead & Centre for Cardiovascular Genetics, University College, London

The impact of the angiotensin converting enzyme gene polymorphism on skeletal and cardiac muscle

function in children with Cystic Fibrosis                               

$20,720

 

A/Prof P Robinson, Dr M. Ditchfield, Dr H. Tiddens

Royal Children’s Hospital, Melbourne

Computed tomographic airway morphometry as an assessment tool of early airway disease in CF.

2nd year  $77, 117

 

2004 Projects Funded - $480,429

A/Prof P Bye, A/Prof C. Harbour, Dr  M. Robinson,

Dr B. Rose, A/Prof R. Benn, A/Prof S. Bell

Royal Prince Alfred Hospital Camperdown

Multiple combination bactericidal testing in CF: a randomised trial                                                                                    

Total $134,000 2nd year funding $69,000 

Women’s & Children’s Hospital, Adelaide

Lasting gene therapy for CF airway disease

$20,000

A/Prof S Kirov, Dr D. Reid

University of Tasmania,  Hobart

Pseudomonas biofilm growth and pathogenesis in cystic

fibrosis                  

$58,757

Ms J. Glazner

Royal Children’s Hospital, Melbourne

The impact of cystic fibrosis on sibling relationships

$32,892

Dr E Tovey, A/Prof P. Bye, Dr  P. Cooper

Woolcock Institute of Medical Research, Royal Prince Alfred

Hospital, Camperdown                                                                                                                              
Fungal exposure and fungal-specific IgE in subjects with cystic fibrosis

$66,500

Dr S. Brennan, DR J. Upham, Dr S Stick, Mr M. Wikstrom

Institute for Child Health Research, Perth

Immune surveillance in CF – the role of macrophages and dendritic cells

$62,896

A/Prof P. Robinson, Dr M. Ditchfield, Dr H. Tiddens

Royal Children’s Hospital, Melbourne

Computed tomographic airway morphometry as an assessment tool of early airway disease in CF

Total $171,384 funded over 2 years     1st Year $94,267

 

2003 Projects Funded - $405,524

Dr K. Waters, Dr P. Cooper,

The Children’s Hospital at Westmead

 Cross-sectional review to detect respiratory failure in early adolescence   

Total $113,556, 2nd year funding $72,510

The Rotary Club of Cobar Project

Dr B. Rose, A/ Prof. C Herbour, A/Prof P. Bye, Dr J. Iredell, A/Prof S.Bell    

Royal Prince Alfred Hospital, Camperdown

Antibiotic Resistance and cross infection in Pseudomonas Aeruginosa from Cystic Fibrosis patients

A/Prof P. Bye, A/Prof C. Harbour, Dr M. Robinson,

Dr B Rose, A/Prof R Benn, A/Prof S Bell

Royal Prince Alfred Hospital Camperdown

Multiple combination bactericidal testing in CF: a randomised trial

Total funded over 2 tears $134,000   1st year $65,000                                                                  

Dr A. McWilliam, Prof G. Stewart

University of Western Australia, QE11 Medical Centre

Bacterial DNA as a modulator of respiratory epithelial Cell function                                            

$86,000

Dr G. Hall, Dr A. Moeller, Dr S. Stick

University of Western Australia (Princess Margaret

Hospital for Children) Perth

Validation of breath condensates to track lung Inflammation in CF                                              

$43,014 

 

2002 Projects Funded  - $328,054

Dr K. Waters, Dr P. Cooper,

The Children’s Hospital at Westmead

Cross-sectional review to detect respiratoryfailure in early adolescence

Total $113,556 funded over 2 years         1st year funding $41,046                                                                                            

Dr S. Stick, Dr Legg

TVW Telethon Institute for Child Health, Perth

Epithelial synthesis and production of nitricoxide in infants with Cystic Fibrosis ACFRT

$32,545

A/Prof. C. Harbour, Dr B. Rose,

A/Prof P. Bye, A/Prof R. Benn

The University of Sydney 

Synergy testing of multidrug resistant bacteria in

$53,220

A/Prof J. McCormack, Dr S. Bowler,

Dr S. Bell, Miss S. Seeney, Mrs K. Walmsley

The Mater Hospital, Brisbane

A randomised double-blind trial of long-term daily versus weekly Azithromycin in CF                                  

$85,904          

Prof P. Sly, Dr S. Brennan, Dr N. Kent

Institute for Child Health Research, Perth

Urinary markers of lung tissue destructionin CF                                                                                                                                          

$42,829