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
Se015: A Developmental Drug For The Treatment Of Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$304,206.00
Summary
Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with ....Primary malignant brain tumors are amongst the most lethal forms of human cancers with median survival for these patients being only around 1 year. In spite of the advent of new targeted therapies for some cancers the prognosis for these patients remains dismal. Worldwide, more than 95% of all people who contract the disease will die of it. This is because there are no effective therapies and all current treatments are only palliative, seeking to lesson the distressing suffering associated with disease progression. Nearly all therapies that have shown some efficacy in treating cancer, such as chemotherapy and radiation have a mode of action whereby they attempt to kill cancer cells by inflicting enough damage to the cancer cells that they induce them to commit cell suicide, a process called apoptosis. Unfortunately, cancer cells can become resistant to these therapies by activating the cells' own signaling pathways that normally block apoptosis. One of the key pathways that has been implicated in resistance to apoptosis in human cancers is the PI3K-Akt pathway. This pathway is overactivated in many advanced human tumors, particularly in glioblastoma. We have discovered a compound, Se015, which can effecitively block this pathway in brain cancer cells and is able to dramatically improve the effectiveness of both chemotherapy and radiation in killing these cells. We have confirmed the efectiveness of Se015 in preliminary animal models of brain cancer, where we have shown that Se015 demonstrated no noticeable toxicity and was active when taken orally. We now need to explore further the molecular mode of action of Se015, as well as complete our animal studies with the eventual aim of initiating a small trial of Se015 in glioblastoma patients in the forseeable future.Read moreRead less
Research & Training To Reduce Morbidity & Mortality From Malaria In Papua ( Indonesia)& Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$1,649,828.00
Summary
Malaria kills many thousands of people each year in Indonesia and PNG. This project will look at better ways to treat and prevent malaria. The team will examine whether using new combinations of drugs in clinics can reduce the amount of severe malaria seen in Papua. The team will examine whether giving people with severe malaria arginine, a naturally occurring amino acid, can increase molecules that may protect against severe malaria. Finally it will examine how lung damage occurs in people with ....Malaria kills many thousands of people each year in Indonesia and PNG. This project will look at better ways to treat and prevent malaria. The team will examine whether using new combinations of drugs in clinics can reduce the amount of severe malaria seen in Papua. The team will examine whether giving people with severe malaria arginine, a naturally occurring amino acid, can increase molecules that may protect against severe malaria. Finally it will examine how lung damage occurs in people with severe malaria and whether this can be predicted.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.