UQCCR Seminar Series with Dr Mohd Hafiz Abdul-Aziz and Dr Brian Forde

Prolonged infusions of beta-lactam antibiotics in sepsis with Dr Mohd Hafiz Abdul-Aziz   
Bio: Dr. Mohd Hafiz Abdul-Aziz is an Early Career Research Fellow and Clinical Research Pharmacist at the University of Queensland Centre for Clinical Research (UQCCR), Australia. He currently leads the Clinical Dosing Studies and Knowledge Translation Workstream within the Antimicrobial Optimisation Group and the Centre for Research Excellence for Personalising Antimicrobial Dosing to Reduce Resistance (CRE RESPOND) at UQCCR. As a clinical pharmacist with a strong interest in clinical research, Dr. Abdul-Aziz is particularly focused on multi-centre and multi-national collaborations. His current research program aims to develop innovative methods for optimising antimicrobial dosing and delivery to improve patient outcomes in the ICU. He has extensive experience in designing and conducting multi-national clinical pharmacokinetic studies in the ICU. Over the past five years, he has led or coordinated eight multi-national antimicrobial pharmacokinetic studies, including the ASAP ECMO, BLING 3, BLING 3 PK/PD, and PNEUDOS studies. 

Enhancing the efficacy of Cefiderocol using ionophores with Dr Brian Forde   
Bio: Brian Forde is a Group Leader and  Senior Research Fellow in Microbial Genomic and Bioinformatics at the UQ Institute for Molecular Bioscience (IMB). His research focuses on microbial genomics and Bioinformatics, with key areas including patho-genomics, antimicrobial resistance (AMR), genomic epidemiology, genomic surveillance of Infectious Diseases and high-throughput microbial genomics for vaccine discovery. In addition to his research CI Forde leads the development of custom software and analysis pipelines for genomic research. These include a NATA accredited genomic analysis and visualisation platform facilitating the implemtation of infectious diseases genomics into routine clinical practice. 
Brief overview: Infections due to A. baumannii are burdened by high mortality rates and are rapidly increasing worldwide. Carbapenem resistant A. baumannii (CR-AB) infections are especially challenging and are identified as a critical priority by WHO on its priority pathogens list for R&D of new antibiotics. Compared to carbapenem-sensitive A. baumannii, the presence of carbapenem resistance is independently associated with increased mortality. Cefiderocol (CFD), a novel cephalosporin, shows promising efficacy against Gram-negative bacteria, including CR-AB. However, therapeutic failures have been observed, even amongst susceptible strains of CR-AB. The safe-for-human-use 8-hydroxyquinoline ionophores (8HQs), such as PBT2, have previously been shown to induce an iron-starvation response in CR-AB and induce upregulation of the acinetobactin ferric iron-import system involved in cefiderocol uptake. Here, 8HQs were observed to break cefiderocol resistance in cefiderocol-resistant A. baumannii clinical isolates, in vitro. Notably, using a cefiderocol-resistant clinical strain of CR-AB, we demonstrate that 8HQs can potentiate cefiderocol antibiotic activity in a murine model of A. baumannii pulmonary infection. These findings provide a treatment modality to rescue and prolong the efficacy of this promising novel antibiotic therapeutic.