Management Of Burn Injury: Fluid Dynamics And Antibiotic Pharmacokinetics
Funder
National Health and Medical Research Council
Funding Amount
$342,375.00
Summary
It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and immunologic alterations occurring both at the wound site and, more importantly, in other body compartments and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition to significant fluid loss. The distribution of inflammatory med ....It is well known that major burns, as well as being relatively common injuries, are notoriously difficult to manage. Patients exhibit significant variability due to a combination of anatomic, physiologic, hormonal and immunologic alterations occurring both at the wound site and, more importantly, in other body compartments and vital organ systems. Skin burn injury results in the release of multiple inflammatory mediators in addition to significant fluid loss. The distribution of inflammatory mediators and wound bacteria to central organs can cause complex physiological changes that may lead to multiple organ failure, with serious infections occurring in around 50% of patients with serious burns. Antibiotic distribution kinetics, such as bioavailability, clearance, volume of distribution, elimination half-life and unbound fraction in plasma can be significantly altered in burn patients. Without detailed knowledge of changes and relationships between factors such as wound pH, tissue oxygenation, protein concentrations of fluid leaked from the local wound microvasculature, tissue binding, oedema and changes in burned and non-burned tissue induced by resuscitation therapies, the optimisation of both local and systemic infection contriol therapies can hardly be expected to advance. This project aims to determine how changes the physiology of burn patients, in particular in the burn wound environment, affect antibiotic penetration and distribution into tissues. We also believe that these changes will vary between patients and are aiming to determine whether certain parameters can be used to give an indication of the best antibiotic dosing regimens for individual patients.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.
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.
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.
Centre For REdefining Antibiotic Use To ReDUce ResistanCE And Prolong The Lives Of Antibiotics (REDUCE)
Funder
National Health and Medical Research Council
Funding Amount
$2,158,296.00
Summary
Ineffective dosing of antimicrobials has contributed to the escalation of antimicrobial resistance which now pervades the healthcare system. Patients in the intensive care unit and post-transplant are examples of patients who commonly have infections, are more likely to fail treatment and have resistant microbes emerge. In these studies we will characterise the doses of antimicrobials that should be used in these difficult-to-treat patients and rapidly share these for routine clinical use.
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.
Ineffective antibiotic therapy is associated with increased mortality in infected patients in the intensive care unit (ICU). Early administration of efficacious antibiotic therapy improves survival substantially. This work seeks to extend upon my previous studies that have described the different concentrations of antibiotics between ICU patients and non-ICU patients. Predicting when to change antibiotic doses in ICU patients is likely to substantially improve patient outcomes.