Molecular Genetics And Evolution Of Antibiotic Resistant Staphylococci
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Potentially life-threatening infections caused by Staphylococcus aureus bacteria, commonly known as Golden Staph, often arise as complications in patients within hospitals. These infections compromise the health of the patient and jeopardise their recovery from the condition for which they were initially admitted, which significantly increases healthcare costs. Golden Staph is a major cause of hospital-acquired infections in Australia and globally. The problem is largely due to the presence in h ....Potentially life-threatening infections caused by Staphylococcus aureus bacteria, commonly known as Golden Staph, often arise as complications in patients within hospitals. These infections compromise the health of the patient and jeopardise their recovery from the condition for which they were initially admitted, which significantly increases healthcare costs. Golden Staph is a major cause of hospital-acquired infections in Australia and globally. The problem is largely due to the presence in hospitals of strains that are resistant to most clinically-useful antibiotics and are therefore very difficult to eradicate; the recent isolation of strains highly-resistant to one of the last resort anti-staphylococcal antibiotics, vancomycin, is particularly worrying. The emergence of these multiresistant strains is primarily attributable to the acquisition of pre-existing resistance determinants by cell-to-cell gene transfer, a process in which plasmids, extra-chromosomal DNA elements, play a prominent role. Staphylococcal multiresistance plasmids carry genes that can confer resistance to up to 20 antimicrobial agents and are themselves capable of transfer between bacterial cells. In this project, we will define the molecular mechanisms by which staphylococcal multiresistance plasmids efficiently replicate in the host cell and are stably maintained in growing bacterial populations or when acquired by a new host after transfer; such mechanisms may well provide novel drug targets. The results will also lead to the development of improved methods for the characterisation of clinical strains and the monitoring of antibiotic resistance, and will be of broad relevance to the problem of antimicrobial resistance in bacterial pathogens. Most importantly, the application of knowledge arising from these studies to the design and implementation of rational antibiotic usage policies has the potential to extend the efficacy of existing and future anti-staphylococcal therapies.Read moreRead less
DNA Segregation In Multiresistant Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$306,592.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of hospital-acquired, and increasingly community-acquired, infections in Australia and around the world. Bacterial growth depends on the faithful inheritance of genetic material, which is facilitated by active DNA segregation. This project will elucidate key aspects of segregation processes so that treatments can be devised that interfere with the growth of this important pathogen and the development of resistance.
A Trial Of Therapeutic Drug Monitoring In Methadone Maintenance Treatment
Funder
National Health and Medical Research Council
Funding Amount
$542,025.00
Summary
Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to ....Heroin addiction is an established and increasing problem in developed countries and in many developing nations. Although there have been several new treatments for heroin addiction, methadone maintenance remains the most effective way to minimize the harms associated with heroin addiction. The current research proposal seeks to test a new approach to setting of methadone dose, using monitoring of methadone blood levels, effects and side-effects in determining when to increase doses, and when to switch to alternative therapies. This provides an objective method of planning treatment that focuses on suppressing heroin use. The potential subjects of the study are the 50% of patients who continue to use heroin regularly during treatment. All will undergo assessment involving measurement of blood levels of methadone, testing of effects and side-effects of methadone, and monitoring of safety. Half will be randomly allocated to usual care, and half to therapeutic drug monitoring, with dose adjustments according to the results of testing. At 3 and 6 months all subjects will undergo repeat test sessions. It is hypothesized that those in the experimental group will be using less heroin (confirmed by hair testing). It is expected that the study will also identify a small group of subjects with genetically different opioid receptors, who will require very high doses of methadone to be stabilized. The study will allow a detailed analysis of how best to monitor dose adequacy; the relationship between withdrawal symptoms, methadone blood levels, and heroin use, and will provide the first clear investigation of the relationship between changes in methadone blood concentration and certain potentially dangerous changes in the electrical activity of the heart. The intended outcome of this research project is a model for a higher standard methadone program that is more effective in reducing the problems of heroin use in our community.Read moreRead less