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Novel Therapeutic Strategy Against Multidrug-resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$349,823.00
Summary
In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the l ....In the past two decades, there has been a marked decline in discovery and development of new antibiotics while there has been a remarkable increase in resistance to the currently available antibiotics. The growth in the number of resistant bacteria and lack of antibiotics available for treatment is very significant with gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Colistin, an old antibiotic that has been used little over the last 40-50 years, has been 'taken off the shelf' and is now being used as a last line of defence to treat people with infections caused by these bacteria. Clearly, doctors and their infected patients will be in an even more precarious position than currently exists if resistance to colistin increases. We have discovered a novel therapeutic strategy that is able to reverse colistin resistance in P. aeruginosa. The studies proposed in this project will investigate this novel strategy across a range of multidrug-resistant bacteria and provide the information essential for rational use in patients. We propose that such a novel therapeutic strategy will provide a powerful weapon for the war on these 'superbugs'.Read moreRead less
Towards Optimising Dosing Of The 'old' Antibiotic Colistin Methanesulphonate: Enhancing Efficacy And Reducing Resistance
Funder
National Health and Medical Research Council
Funding Amount
$266,500.00
Summary
The global problem of multidrug-resistant bacteria is a major clinical challenge. In cystic fibrosis (CF) patients, the bacteria pseudomonas shows significantly high resistance to the commonly used antibiotics and is a major cause of death. As a consequence, interest in an old antibiotic, colistin, has been rekindled after 40 years on the shelf. The safety of intravenous colistin has been demonstrated in several clinical trials. However, based on our preliminary studies in CF patients, the curre ....The global problem of multidrug-resistant bacteria is a major clinical challenge. In cystic fibrosis (CF) patients, the bacteria pseudomonas shows significantly high resistance to the commonly used antibiotics and is a major cause of death. As a consequence, interest in an old antibiotic, colistin, has been rekindled after 40 years on the shelf. The safety of intravenous colistin has been demonstrated in several clinical trials. However, based on our preliminary studies in CF patients, the current dosage regimen where colistin is given three times a day does not achieve high enough concentrations to kill the bacteria. The studies proposed in this project will address the safety, effectivenss and impact on development of resistance of larger doses of intravenous colistin given once or twice daily. We propose that such dosing strategies will yield more effective usage of this promising 'old' antibiotic.Read moreRead less
Value Of Androgen Deprivation And Bisphosphonate Therapy In Patients Treated By Radiotherapy For Limited Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,757,375.00
Summary
Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation'[AD] therapy) can produce clinically important shrinkage of prostate cancer. Each year approximately 4000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Results from recent trials, including a large trial run in Au ....Prostate cancer depends for its growth on the male hormone, testosterone, which circulates in the blood. As a result treatment which reduces testosterone level ('androgen deprivation'[AD] therapy) can produce clinically important shrinkage of prostate cancer. Each year approximately 4000 men in Australia and New Zealand develop prostate cancer which has not spread widely and which is amenable to attempted cure by surgery or radiation. Results from recent trials, including a large trial run in Australia and New Zealand by the Trans-Tasman Radiation Oncology Group (TROG) between 1996 and 2000, suggest that 6 months AD will benefit many of these men if administered in conjunction with radiotherapy.The aim of this project is to run a further trial to find out whether 12 months of AD, after radiotherapy will prevent the need for further treatment and prolong more lives than only 6 months AD. Bisphosphonate treatment also offers important benefits to prostate cancer patients because it can increase bony stregth by increasing its density and can also arrest cancerous growth in bones. A further aim of the trial therefore is to determine whether 18 months of bisphosphonate therapy (BP) will prevent bone loss (osteoporosis) caused by AD, and also further reduce the risk of secondary bone cancer developing. This trial will involve recruitment of 1000 men across Australia and New Zealand over a 5 year period. When complete the trial will determine whether further treatment can be delayed and life prolonged in up to half of all men in whom treatment presently fails. This grant will support collection of patient data and the necessary quality checks to ensure that reliable conclusions can be drawn.Read moreRead less
Antimicrobial Stewardship - Establishing Effective Programs For Australian Hospitals
Funder
National Health and Medical Research Council
Funding Amount
$1,232,361.00
Summary
This project will examine strategies to improve the use of antimicrobial drugs in Australian hospitals. It will evaluate the impact of antimicrobial stewardship programs on antibiotic prescribing practices in Victorian tertiary hospitals and determine the organisational factors associated with success. It will also examine the needs, and establish models for antimicrobial stewardship beyond the tertiary hospital setting, in private hospitals, small metropolitan and rural hospitals.
The Epidemiology And Treatment Of Infections Due To Multiresistant Gram Negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$274,946.00
Summary
This fellowship application deals with the treatment of infections due to antibiotic resistant bacteria. The World Economic Forum recently discussed threats to our modern way of life. The highest ranked threats were climate change, terrorism and antibiotic resistance. During this Fellowship, two large clinical trials of treatment strategies for antibiotic resistant bacteria will be supervised by Professor Paterson.
Rescuing The Last-line Therapy Colistin Against Gram-negative ‘superbugs’: Increasing The Therapeutic Index By Attenuation Of Nephrotoxicity
Funder
National Health and Medical Research Council
Funding Amount
$498,631.00
Summary
Antibiotic resistance in Gram-negative ‘superbugs’ is presenting a significant global medical challenge. Colistin (polymyxin E) is increasingly used as the last treatment option even though the current use is suboptimal. Simply increasing the daily dose is not an option due to kidney toxicity. This project focuses on a new approach using antioxidants to ameliorate the potential for colistin-induced kidney toxicity, thereby allowing higher doses to achieve adequate bacterial kill in patients.
Targeting The Achilles' Heel Of Polymyxins: Eliminating The Nephrotoxicity
Funder
National Health and Medical Research Council
Funding Amount
$673,420.00
Summary
The world is facing a growing threat from the emergence of bacterial 'superbugs' that are resistant to all current antibiotics except the polymyxins. However, kidney toxicity occurs in up to 60% of patients receiving intravenous polymyxins. In this project, we will examine how polymyxins cause kidney toxicity then employ the obtained mechanistic information to decrease this adverse effect. Our study targets the urgent global unmet medical need, lack of new antibiotics for bacterial ‘superbugs’.
Optimising Inhaled Polymyxins As A Vital Therapy For Pulmonary Infections: A Novel Biochemical, Molecular Imaging And Systems Pharmacology Approach
Funder
National Health and Medical Research Council
Funding Amount
$728,044.00
Summary
Lung infection is a leading cause of death in Australia and globally. Many bacterial pathogens are resistant to almost all current antibiotics. A class of ‘old’ antibiotics, polymyxins, are the last option for bacterial ‘superbugs’. Unfortunately, the current use of polymyxins is suboptimal and can cause severe kidney toxicity. This multi-disciplinary project will apply cutting-edge techniques to optimise inhaled polymyxin therapy for treatment of life-threatening pulmonary infections.
Antibiotic Allergy Testing And Its Impact On Antimicrobial Stewardship In The Immunocompromised Host
Funder
National Health and Medical Research Council
Funding Amount
$124,714.00
Summary
While antibiotic allergy labels are common, the impact on immunosuppressed patients is unknown. This collaboration between Austin Health, Peter MacCallum Cancer Centre and Vanderbilt University Medical Centre (USA) will be the first Australian assessment of the impacts of antibiotic allergy labels on immunosuppressed patients. This project will provide strategies to examine the impact of and revise the antibiotic allergy labels with skin prick allergy testing and advanced immunodiagnostics.
Centre For REdefining Antibiotic Use To ReDUce ResistanCE And Prolong The Lives Of Antibiotics (REDUCE)
Funder
National Health and Medical Research Council
Funding Amount
$2,158,296.00
Summary
Ineffective dosing of antimicrobials has contributed to the escalation of antimicrobial resistance which now pervades the healthcare system. Patients in the intensive care unit and post-transplant are examples of patients who commonly have infections, are more likely to fail treatment and have resistant microbes emerge. In these studies we will characterise the doses of antimicrobials that should be used in these difficult-to-treat patients and rapidly share these for routine clinical use.