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 effect of piperacillin against Pseudomonas aeruginosa evaluated via the hollow-fibre infection model and mechanism-based modelling, Bergen, P.J., Bulitta, J.B., Kirkpatrick, C.M.J., Rogers, K.E., McGregor, M.J., Wallis, S.C., Paterson, D.L., Lipman, J., Roberts, J.A. and Landersdorfer, C.B. J Antimicrob Chemother 2016;71:2509-2520

doi:10.1093/jac/dkw153

2. Abdul-Aziz, M., Sulaiman, H., Mat-Nor, H., Rai, M., Wong, V., Hasan, K., . . . Roberts, 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 Medicine, 42(10), 1535-1545.

DOI: 10.1007/s00134-015-4188-0

3. Tängdén, T., Ramos Martín, V., Felton, T., Nielsen, E., Marchand, S., Brüggemann, R., . . . Roberts, J. (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. Yadav, R., Bulitta, J., Wang, J., Nation, R., & Landersdorfer, C. (2017). Evaluation of Pharmacokinetic/Pharmacodynamic Model-Based Optimized Combination Regimens against Multidrug-Resistant Pseudomonas aeruginosa in a Murine Thigh Infection Model by Using Humanized Dosing Schemes. Antimicrobial Agents and Chemotherapy, 61(12), Antimicrobial agents and chemotherapy, December 2017, Vol.61(12).

DOI: 10.1128/AAC.01268-17