Exploring the impact of altered and variable antimicrobial pharmacokinetics on bacterial killing and emergence of bacterial resistance.
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
Setiawan, Eko, Cotta, Menino Osbert, Roberts, Jason A. and Abdul-Aziz, Mohd Hafiz (2023). A systematic review on antimicrobial pharmacokinetic differences between Asian and non-Asian adult populations. Antibiotics, 12 (5) 803, 1-23. doi: 10.3390/antibiotics12050803
Burke, Andrew, Carter, Robyn, Tolson, Carla, Congdon, Jacob, Duplancic, Christine, Bursle, Evan, Bell, Scott C, Roberts, Jason A. and Thomson, Rachel (2023). In Vitro Susceptibility Testing of Imipenem- Relebactam and Tedizolid against 102 Mycobacterium abscessus isolates. International Journal of Antimicrobial Agents 106938, 106938. doi: 10.1016/j.ijantimicag.2023.106938
Roberts, Jason A, Nicolau, David P, Martin-Loeches, Ignacio, Deryke, C Andrew, Losada, Maria C, Du, Jiejun, Patel, Munjal, Rizk, Matthew L, Paschke, Amanda and Chen, Luke F (2023). Imipenem/cilastatin/relebactam efficacy, safety and probability of target attainment in adults with hospital-acquired or ventilator-associated bacterial pneumonia among patients with baseline renal impairment, normal renal function, and augmented renal clearance. JAC-Antimicrobial Resistance, 5 (2) dlad011. doi: 10.1093/jacamr/dlad011
Sumi, Chandra Datta, Heffernan, Aaron J., Naicker, Saiyuri, Cottrell, Kyra, Wallis, Steven C., Lipman, Jeffrey, Harris, Patrick N. A., Sime, Fekade B. and Roberts, Jason A. (2022). Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Escherichia coli clinical isolates. Journal of Antimicrobial Chemotherapy, 77 (11), 3026-3034. doi: 10.1093/jac/dkac273
Islam, Kamrul, Sime, Fekade B., Wallis, Steven C., Bauer, Michelle J., Naicker, Saiyuri, Won, Hayoung, Zowawi, Hosam M., Choudhury, Md Abu, Shirin, Tahmina, Habib, Zakir H., Harris, Patrick N. A., Flora, Meerjady S. and Roberts, Jason A. (2022). Pharmacodynamics of Piperacillin-Tazobactam/Amikacin Combination versus Meropenem against Extended-Spectrum β-Lactamase-Producing Escherichia coli in a Hollow Fiber Infection Model. Antimicrobial Agents and Chemotherapy, 66 (9), e0016222. doi: 10.1128/aac.00162-22
Karabasevic, Natalija, Roberts, Jason A., Stronach, Luke, Naicker, Saiyuri, Wallis, Steven C., Sjövall, Fredrik and Sime, Fekade (2022). Use of the hollow-fiber infection model to measure the effect of combination therapy of septic shock exposures of Meropenem and Ciprofloxacin against intermediate and resistant Pseudomonas aeruginosa clinical Isolates. Antimicrobial Agents and Chemotherapy, 66 (5) e0214021, e0214021. doi: 10.1128/aac.02140-21
Islam, Kamrul, Sime, Fekade B., Bauer, Michelle J., Forde, Brian M., Wallis, Steven C., Harris, Patrick, Naicker, Saiyuri, Shirin, Tahmina, Habib, Zakir H., Flora, Meerjady S. and Roberts, Jason A. (2022). Pharmacodynamic evaluation of piperacillin/tazobactam against extended-spectrum β-lactamase-producing versus non-producing Escherichia coli in a hollow-fibre infection model. International Journal of Antimicrobial Agents, 60 (2) 106623, 1-7. doi: 10.1016/j.ijantimicag.2022.106623
Islam, Kamrul, Sime, Fekade B., Wallis, Steven C., Bauer, Michelle J., Forde, Brian M., Harris, Patrick, Shirin, Tahmina, Habib, Zakir H., Flora, Meerjady S. and Roberts, Jason A. (2022). Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum β-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model. Journal of Antimicrobial Chemotherapy, 77 (9), 2448-2455. doi: 10.1093/jac/dkac186
Mohd Sazlly Lim, Sazlyna, Heffernan, Aaron, Naicker, Saiyuri, Wallis, Steven, Roberts, Jason A. and Sime, Fekade Bruck (2022). Evaluation of fosfomycin-sulbactam combination therapy against carbapenem-resistant Acinetobacter baumannii isolates in a hollow-fibre infection model. Antibiotics, 11 (11) 1578, 1-11. doi: 10.3390/antibiotics11111578
De Oliveira, David M. P., Forde, Brian M., Phan, Minh-Duy, Steiner, Bernhard, Zhang, Bing, Zuegg, Johannes, El-deeb, Ibrahim M., Li, Gen, Keller, Nadia, Brouwer, Stephan, Harbison-Price, Nichaela, Cork, Amanda J., Bauer, Michelle J., Alquethamy, Saleh F., Beatson, Scott A., Roberts, Jason A., Paterson, David L., McEwan, Alastair G., Blaskovich, Mark A. T., Schembri, Mark A., McDevitt, Christopher A., von Itzstein, Mark and Walker, Mark J. (2022). Rescuing Tetracycline Class Antibiotics for the Treatment of Multidrug-Resistant Acinetobacter baumannii Pulmonary Infection. mBio, 13 (1) e03517, e0351721. doi: 10.1128/mbio.03517-21
Abbott, Iain J., Roberts, Jason A., Meletiadis, Joseph and Peleg, Anton Y. (2021). Antimicrobial pharmacokinetics and preclinical in vitro models to support optimized treatment approaches for uncomplicated lower urinary tract infections. Expert Review of Anti-infective Therapy, 19 (3), 271-295. doi: 10.1080/14787210.2020.1813567
Mohd Sazlly Lim, Sazlyna, Heffernan, Aaron J., Zowawi, Hosam M., Roberts, Jason A. and Sime, Fekade B. (2021). Semi-mechanistic PK/PD modelling of meropenem and sulbactam combination against carbapenem-resistant strains of Acinetobacter baumannii. European Journal of Clinical Microbiology and Infectious Diseases, 40 (9), 1943-1952. doi: 10.1007/s10096-021-04252-z
Mohd Sazlly Lim, S., Heffernan, A.J., Roberts, J.A. and Sime, F.B. (2021). Semi-mechanistic PK/PD modelling of fosfomycin and sulbactam combination against carbapenem-resistant Acinetobacter baumannii. Antimicrobial Agents and Chemotherapy, 65 (5) e02472-20. doi: 10.1128/aac.02472-20
Garbez, Nicolas, Mbatchi, Litaty C., Louart, Guillaume, Wallis, Steven C., Muller, Laurent, Lipman, Jeffrey, Roberts, Jason A., Lefrant, Jean-Yves and Roger, Claire (2021). Micafungin population PK analysis in healthy and septic pigs: can the septic porcine model predict the micafungin PK in septic patients?. Pharmaceutical Research, 38 (11), 1863-1871. doi: 10.1007/s11095-021-03137-2
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 Chemotherapy, 71 9: 2509-2520. doi:10.1093/jac/dkw153
16. 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
17. 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
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 Chemotherapy, 62 5: e00078-18. doi:10.1128/AAC.00078-18
Project members
