Development of resistance during antimicrobial therapy is common.

For the special patient populations studied in this application - adult and paediatric ICU patients, burns, cystic fibrosis, obese, post-transplant, pneumonia and patients receiving renal replacement therapy - prolonged hospital stays are common, exposing the patient to more infections and more antimicrobial courses.

Our previous studies of common antimicrobials, piperacillin and meropenem, have quantified major pharmacokinetic alterations in adult ICU patients, whereby they display a unique spectrum of plasma concentration time profiles. There is a clinical imperative to describe the impact of these altered and highly variable antimicrobial exposures on bacterial killing and the emergence of resistance. This project addresses this considerable knowledge gap and will determine how contemporary antimicrobial dosing in these special patient populations leads to the emergence of resistance. 

Relevant publications

1. Effect of different renal function on antibacterial effects of piperacillin against Pseudomonas aeruginosa evaluated via the hollow-fibre infection model and mechanism-based modelling

Bergen, Phillip J., Bulitta, Jurgen B., Kirkpatrick, Carl M. J., Rogers, Kate E., McGregor, Megan J., Wallis, Steven C., Paterson, David L., Lipman, Jeffrey, Roberts, Jason A. and Landersdorfer, Cornelia B. (2016) Effect of different renal function on antibacterial effects of piperacillin against Pseudomonas aeruginosa evaluated via the hollow-fibre infection model and mechanism-based modelling. Journal of Antimicrobial Chemotherapy71 9: 2509-2520. doi:10.1093/jac/dkw153

2. Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis

Abdul-Aziz, Mohd H., Sulaiman, Helmi, Mat-Nor, Mohd-Basri, Rai, Vineya, Wong, Kang K., Hasan, Mohd S., Abd Rahman, Azrin N., Jamal, Janattul A., Wallis, Steven C., Lipman, Jeffrey, Staatz, Christine E. and Roberts, Jason A. (2016) Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Medicine42 10: 1535-1545. doi:10.1007/s00134-015-4188-0

3. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections

Tangden, T., Ramos Martin, V., Felton, T. W., Nielsen, E. I., Marchand, S., Bruggemann, R. J., Bulitta, J. B., Bassetti, M., Theuretzbacher, U., Tsuji, B. T. (2017). The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections. Intensive Care Medicine 43 (7) 1021-1032. doi:10.10.7/s00134-017-4780-6

4. Xie, Jiao, Roberts, Jason A, Alobaid, Abdulaziz S, Roger, Claire, Wang, Yan, Yang, Qianting, . . . Dong, Yalin. (2017). Population Pharmacokinetics of Tigecycline in Critically Ill Patients with Severe Infections. Antimicrobial Agents and Chemotherapy, 61(8), Antimicrobial agents and chemotherapy, August 2017, Vol.61(8).

DOI: 10.1128/AAC.00345-17

5. Optimization and evaluation of piperacillin plus tobramycin combination dosage regimens againstfor patients with altered pharmacokineticsthe hollow-fiber infection model and mechanism-based modeling

Yadav, Rajbharan, Rogers, Kate E., Bergen, Phillip J., Bulitta, Jürgen B., Kirkpatrick, Carl M. J., Wallis, Steven C., Paterson, David L., Nation, Roger L., Lipman, Jeffrey, Roberts, Jason A. and Landersdorfer, Cornelia B. (2018) Optimization and evaluation of piperacillin plus tobramycin combination dosage regimens againstfor patients with altered pharmacokineticsthe hollow-fiber infection model and mechanism-based modeling. Antimicrobial Agents and Chemotherapy62 5: e00078-18. doi:10.1128/AAC.00078-18