Beta-lactamase Mediated Antibiotic Resistance In Gram-negative Pathogens: How Does Genotype Relate To Phenotype?
Funder
National Health and Medical Research Council
Funding Amount
$397,869.00
Summary
Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expressio ....Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expression of an enzyme called a beta-lactamase. This enzyme breaks down the penicillin. Beta-lactamase enzymes come in many different varieties, and new varieties appear quite frequently. Remarkably, when new kinds of penicillin are invented to circumvent resistance, the appearance of new beta-lactamases that can break down these new penicillins follows shortly thereafter. The objectives of our research are twofold. Firstly, it is now clear that the relationship between the beta-lactamase genes in a bacterium and the resulting pattern of resistance can be very complex. It can involve both the broad nature of the genes, the numbers of duplicates of the genes inside the cell, and very minor changes to the gene sequences. We will probe the relationship between the gene and resistance so as to understand it at a deeper level. Secondly, we will use this information to develop very efficient and cost affective methods for keeping track of the spread of the different varieties of beta-lactamase genes. These methods will be designed to be carried out on real-time PCR machines. These high-tech devices are general purpose gene analyzers that can carry out many different kinds of genetic assay. They are rapidly becoming ubiquitous in clinical microbiology laboratories. The use of these methods will provide much hard information that will be used to minimise the dissemination of antibiotic resistance.Read moreRead less
Gentamicin Vestibulotoxicity: Detection And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$205,500.00
Summary
A powerful, life-saving and cheap antibiotic, gentamicin, has one potential serious permanent side-effect: loss of balance due to damage to the balance organs of the inner ears. Detected early, the inner ear damage can be reversed by stopping gentamicin. Until now there has been no way of monitoring inner ear balance at the bedside. We have now developed such a method and want to show that by monitoring inner ear balance of patients needing gentamicin we can detect damage at such an early stage ....A powerful, life-saving and cheap antibiotic, gentamicin, has one potential serious permanent side-effect: loss of balance due to damage to the balance organs of the inner ears. Detected early, the inner ear damage can be reversed by stopping gentamicin. Until now there has been no way of monitoring inner ear balance at the bedside. We have now developed such a method and want to show that by monitoring inner ear balance of patients needing gentamicin we can detect damage at such an early stage that stopping the drug and using another instead will allow the balance organs to recover by themselves.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.
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.
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.
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.
Understanding Complex Genomic And Biochemical Landscapes In Human Health Microbiology
Funder
National Health and Medical Research Council
Funding Amount
$2,210,520.00
Summary
There is increasing awareness of the critical roles microbes play in health. The microbes in our gut produce chemicals that control everything from our moods, to food metabolism and immune system function. In this proposal leading-edge technologies from the disciplines of microbiology, genomics, mass-spectrometry and computational biology will be used to reveal for the first time how and why these chemicals are produced by microbes in complex systems that are important for human health.
Use Of Molecular Resistance Assays To Provide Alterative Oral Treatment Strategies For Gonorrhoea In Indigenous And Other High-risk Populations; A Randomised Cluster Trial
Funder
National Health and Medical Research Council
Funding Amount
$828,671.00
Summary
Gonorrhoea has now developed resistance to almost all antibiotics that have been used to treat it. In this study, we will investigate a new treatment approach that selects antibiotics on a patient-by-patient basis. We will use new molecular assays to first test if a gonorrhoea strain infecting a patient is susceptible to an antibiotic, and will then treat on the basis of this result. By doing so, we will optimize our use of antibiotics and improve treatment strategies for gonorrhea.