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The Development Of Novel Antibacterials Targeting Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$750,546.00
Summary
Clostridium difficile is a bacterium associated with infections in the gut which may result in mild to severe diarrhoea and inflammation of the colon. These infections are an increasing problem for hospitalised patients in the US, the EU and Australia. We have been very successful in the past at developing new drugs to treat external infections caused by resistant strains of bacteria, for example, golden Staph. We now aim to develop our drugs to treat C. difficile infections in the gut.
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.
How Do Antibiotics Affect The Gastrointestinal Microbiome In Children?
Funder
National Health and Medical Research Council
Funding Amount
$215,000.00
Summary
Antibiotics, while vital, have potentially long term negative effects on antimicrobial resistance and other aspects of health. Microorganisms living in the human intestine, collectively the gastrointestinal microbiome, are believed to play a key role. Antibiotics can change the microbiome, and this is potentially important in children due to the longevity of health effects. We aim to determine the effect of different antibiotics (broad versus narrow) on the microbiome over time in children.
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.
Antibiotic Resistance And The Ecological Effects Of Selective Decontamination Of The Digestive Tract In Intensive Care Units
Funder
National Health and Medical Research Council
Funding Amount
$901,396.00
Summary
We will study patients within a large trial of gut decontamination, in which antibiotics are given in advance to reduce the risk of infection. Specifically, we will determine whether there is any increased antibiotic resistance and even biodiversity loss, as some fear. This is a one-off chance to provide essential data that can help us design better national policies for antibiotic resistance control and a true personalised medicine approach to resistance and infection in ICU.
Innovative Dosing Approaches To Maximise Bacterial Killing And Prevent Resistance In Septic Critically Ill Patients.
Funder
National Health and Medical Research Council
Funding Amount
$830,364.00
Summary
Patients in the intensive care unit (ICU) frequently die from infection. It remains unknown how important antibiotic dose optimisation is for these patients and whether it may enable more effective treatment. In this project, we propose to compare existing approaches to antibiotic dosing in ICU patients with innovative alternatives. We will determine which dosing approach results in better antibacterial efficacy and reduce the development of antibiotic resistance.
From Lead Compounds To Potential Therapeutics: Drugs To Treat Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$523,460.00
Summary
Clostridium difficile infection (CDI) attacks the gut resulting in diarrhoea and inflammation of the colon. It is classified as the number one antibiotic-resistant bacterial threat in the USA where there are 500,000 cases of CDI and 30,000 deaths. CDI is an increasing problem for hospitalized patients in the US, the EU and Australia. Our recent NHMRC funded project established drug leads against CDI and we now require continued studies to develop our drug leads towards marketable therapeutics.
A New Mechanism For Transposition Of Antibiotic Resistance Genes
Funder
National Health and Medical Research Council
Funding Amount
$501,839.00
Summary
Understanding how antibiotic resistance genes are acquired by bacteria is important if we are to understand how bacteria become resistant in so many antibiotics, limiting treatment options. This project will investigate the way a family of insertion sequences captures and then moves resistance genes. This mechanism contributes to resistance in many bacterial pathogens including ones that are resistant to many different antibiotics.