NHMRC Career Development Fellowship (Clinical; Level 1): Antibiotic optimisation for severely ill patients (2013-2016)

Inadequate antibiotic therapy is a critical determinant of survival in patients admitted to an intensive care unit (ICU) with overwhelming infection. Early administration of efficacious antibiotic therapy improves survival substantially. In my previous studies I have highlighted the differences in pharmacokinetics (PK) between ICU patients and non-ICU patients. These PK differences lead to a unique spectrum of plasma concentration time profiles encountered in ICU patients which arises from a very wide range of pathologies and organ function. This unique PK will in part be responsible for the poorer outcomes for ICU patients. A thorough understanding of the altered PK in ICU patients can enable the development of patient-specific dosing approaches that may substantially improve patient outcomes. Aims: 1: Developing a mechanistic understanding of the interrelationship critical illness-related physiological changes on antibiotic PK variability. These projects will produce data, which quantify the effect of altered organ function on the PK of antibiotics in ICU patients. 2: Describing extent of PK variability in different ICU patient populations and providing robust dosing solutions. These projects will produce evidence-based dosing algorithms in various ICU patient groups that will enable more effective antibiotic therapy. 3: Testing methods for antibiotic dose optimization in critically ill patients. These projects will produce robust data defining the role of altered approaches to administering beta-lactams (continuous infusion), as well as the role of therapeutic drug monitoring. 4: Development of new antibiotics. This aim will identify lead compounds for treatment of resistant Gram positive bacterial infections for evaluation in pre-clinical studies. I believe that these studies are of global scientific and clinical importance and have a very high likelihood to substantially improve antibiotic therapy in ICU patients and save lives.