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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’.
Optimisation Of Antimicrobial Therapy For Severe Bacterial Infections In Neonates And Young Children In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$943,865.00
Summary
This study aims to provide important information on the way young Papua New Guinean children with serious bacterial infections handle antibiotics, including newer agents that may be required if bacterial resistance is confirmed or increases. The data will be used to optimise treatment, thus reducing mortality and potential adverse drug effects, in PNG nad other tropical countries, and may have implications for the developed world as well.
Targeting Hypermutable ‘superbugs’ In Chronic Respiratory Infections By Optimised Antibiotic Combination Dosage Regimens
Funder
National Health and Medical Research Council
Funding Amount
$697,731.00
Summary
Many bacterial ‘superbugs’ can increase their mutation rate, i.e. become hypermutable, and thus rapidly become resistant to multiple antibiotics. Chronic lung infections with hypermutable bacteria cause increased ill-health and death in patients and current treatments do not work well. We will develop improved treatments using combinations of available antibiotics. This project will provide guidance to doctors on how to treat infections more effectively and minimise emergence of resistance.
Targeting NDM-producing ‘superbugs’: Optimising Novel Combinations With ‘old’ Polymyxins Using Pharmacological, Molecular Imaging And Systems Biology Approaches
Funder
National Health and Medical Research Council
Funding Amount
$582,732.00
Summary
Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these ver ....Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these very problematic infections.Read moreRead less
Exploiting The Pharmacokinetic And Pharmacodynamic Properties Of Bile Acid Receptor Agonists To Treat Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$653,952.00
Summary
We have generated preliminary data suggesting that chemicals made by the liver, called bile acids, act on fat cells to release a hormone called adiponectin. In liver disease adiponectin has favorable effects, including reducing liver inflammation and fibrosis (scarring). By using drugs that mimic the action of bile acids we expect that adiponectin production by fat cells can be increased, creating a new way to treat patients with chronic liver diseases.
A Study Of Artemisinin Combination Therapy Given At Delivery To Prevent Postpartum Malaria And To Young Infants To Treat Uncomplicated Malaria
Funder
National Health and Medical Research Council
Funding Amount
$788,850.00
Summary
The proposed studies will investigate the preventive value of a course of combination antimalarial treatment at delivery in pregnant women in malarial areas. The transfer of this treatment into breast milk and to the suckling infant will be investigated since this may protect the infant against malaria but also cause drug-related side-effects. These data will be used, with a study of combination treatment in infants with malaria, to optimise dose regimens in this vulnerable group.
Physiologically-based Pharmacokinetics And Pharmacodynamics Of Therapeutic Stem Cells For Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$848,710.00
Summary
This project focuses on the challenging area of effective and optimal dosing cell-based therapy for liver diseases. We will investigate the fate and therapeutic effects of natural, modified and artificial therapeutic cells in the body and in liver regions using a physiologically-based kinetic model. Our key goal is advance cell therapy by providing a better understanding and dosing guidelines.
Improving The Treatment Of Breathlessness – A Phase III Randomised, Controlled Trial Of Sustained Release Morphine For The Symptomatic Treatment Of Chronic Refractory Breathlessness. A Palliative Care Clinical Studies Collaborative Study
Funder
National Health and Medical Research Council
Funding Amount
$902,732.00
Summary
More than 300000 Australians are chronically short of breath at rest or on minimal exertion despite optimal treatment of the underlying causes of their breathlessness, of whom 70000 cannot leave home. No medication in the world is registered to treat this. There is evidence that regular, low dose morphine safely helps breathlessness. This study will help clinicians adjust doses more effectively and understand whether using an additional medication to reduce anxiety helps relieve breathlessness.
Octapeptin-based Antibiotics Against Multi-drug Resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$767,504.00
Summary
Infectious disease is a leading cause of death, and the emergence of "superbugs" in the community and hospitals is of grave concern. We have resurrected a ‘forgotten’ antibiotic from the 1970s that kills superbugs causing pneumonia, skin and urinary track infections; diseases that cause death and discomfort for thousands of Australians today. We will determine how the original antibiotic works against superbugs, and use this information to design better drugs for the future.