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.
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.
Antibiotic resistance increases mortality and costs in the Intensive Care Unit (ICU), but the impact of antibiotic therapy has not been adequately studied. We propose to characterise the behaviour of key elements of the bacterial microflora (resistant bacteria and major resistance genes) in response to antibiotics. We have developed new rapid diagnostics to harness these data and this proposal has the potential to greatly improve diagnostic speed and accuracy and thus clinical outcomes.
OctapeptinX Potentiators To Treat XDR Gram-negative Infections
Funder
National Health and Medical Research Council
Funding Amount
$1,377,149.00
Summary
There is an urgent need for the development of new antibiotics to treat drug-resistant infections, with the World Health Organisation and other agencies warning of a critical threat to human health. Potentiators are drugs that help obsolete antibiotics regain activity against resistant bacteria. We aim to develop a novel class of potentiators, the octapeptins, to resurrect the activity of old antibiotics so they can be used to treat infections caused by highly-resistant Gram-negative bacteria.
Potent Antibiotics Against Drug-resistant Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$531,410.00
Summary
Tuberculosis (TB) is a significant killer and caused 1.7 million deaths in 2009. The disease affects all countries, including Australia, in which the incidence in the indigenous population is 14 times higher than that in the non-indigenous population. We will develop a new anti-TB drug that can replace or enhance the current drugs that are not effective against drug resistant TB.
The Hunt For New-generation Lipopeptide Antibiotics Targeting Gram-negative ‘Superbugs’
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
The dry antibiotic discovery and development pipeline, together with the increasing incidence of bacterial resistance in the clinic has been dubbed ‘the perfect storm’. This project involves the design, synthesis and preclinical evaluation of a new generation of polymyxin-like lipopeptides that have low nephrotoxicity and specifically target polymyxin-resistant Gram-negative ‘superbugs’.
An Integrated Approach To Combat Antibiotic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$389,120.00
Summary
The development of antibiotics such as penicillin was hailed as one of the great breakthroughs in medicine. However, an increasing number of pathogens have acquired resistance to these drugs. One of the most common resistance mechanisms employed by these pathogens is the use of metal dependent enzymes that promote the degradation of antibiotics. To date, no clinically useful inhibitors for these enzymes are available. In this project, we aim to develop such inhibitors as therapeutic drug leads.
Reversing Antibiotic Resistance With Efflux Pump Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$494,174.00
Summary
Antibiotic resistance in dangerous pathogens is one of the greatest threats to human health of the 21st century. The main cause of multidrug resistance is the presence of drug efflux pumps, which remove antibiotics from the bacterial cell thereby lowering the antibiotic concentration inside the cells to sub-toxic levels. We will use our expertise on these efflux pumps and on how to inhibit them to develop compounds that could reverse resistance and restore the activity of antibiotics.
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.