Therapeutic drug monitoring optimisation of antimicrobial exposures for critically ill, burns and transplant patients.
An essential component of the translation of the new knowledge generated by the CRE REDUCE will be to test the clinical safety and tolerability of the novel doses that aim to suppress the emergence of resistance.
Previous in vitro studies that have attempted to quantify the relationship between pharmacokinetics and pharmacodynamics and the development of resistance have mostly found that higher antimicrobial exposures are required. Since higher drug exposures lead to concerns for patient safety this multi-centre study will use therapeutic drug monitoring or TDM to optimize antimicrobial exposures and test for the safety and tolerability of the new doses.
Relevant Publications
Cojutti, Pier Giorgio, Heffernan, Aaron J., Tängdén, Thomas, Della Siega, Paola, Tascini, Carlo, Roberts, Jason A. and Pea, Federico (2023). Population Pharmacokinetic and Pharmacodynamic Analysis of Valganciclovir for Optimizing Preemptive Therapy of Cytomegalovirus Infections in Kidney Transplant Recipients. Antimicrobial Agents and Chemotherapy, 67 (3). doi: 10.1128/aac.01665-22
Chai, Ming G, Roberts, Jason A, Farkas, Andras and Cotta, Menino O (2023). Accuracy of a precision dosing software program for predicting antibiotic concentrations in critically ill patients. Journal of Antimicrobial Chemotherapy, 78 (2), 354-358. doi: 10.1093/jac/dkac392
Barreto, Erin F., Chitre, Pooja N., Pine, Kathleen H., Shepel, Kathryn K., Rule, Andrew D., Alshaer, Mohammad H., Abdul Aziz, Mohd Hafiz, Roberts, Jason A., Scheetz, Marc H., Ausman, Sara E., Moreland-Head, Lindsay N., Rivera, Christina G., Jannetto, Paul J., Mara, Kristin C. and Boehmer, Kasey R. (2023). Why is the implementation of beta-lactam therapeutic drug monitoring for the critically ill falling short? A multicenter mixed-methods study. Therapeutic Drug Monitoring, Publish Ahead of Print (4), 508-518. doi: 10.1097/FTD.0000000000001059
Antifungal dosing in critically ill patients on extracorporeal membrane oxygenation
Lyster, Haifa, Shekar, Kiran, Watt, Kevin, Reed, Anna, Roberts, Jason A. and Abdul-Aziz, Mohd-Hafiz (2023). Antifungal dosing in critically ill patients on extracorporeal membrane oxygenation. Clinical Pharmacokinetics, 62 (7), 931-942. doi: 10.1007/s40262-023-01264-0
Multicenter population pharmacokinetic study of unbound ceftriaxone in critically ill patients
Heffernan, Aaron J., Sime, Fekade B., Kumta, Nilesh, Wallis, Steven C., McWhinney, Brett, Ungerer, Jacobus, Wong, Gloria, Joynt, Gavin M., Lipman, Jeffrey and Roberts, Jason A. (2022). Multicenter population pharmacokinetic study of unbound ceftriaxone in critically ill patients. Antimicrobial Agents and Chemotherapy, 66 (6), e0218921. doi: 10.1128/aac.02189-21
Cheng, Vesa, Abdul-Aziz, Mohd H., Burrows, Fay, Buscher, Hergen, Cho, Young-Jae, Corley, Amanda, Diehl, Arne, Gilder, Eileen, Jakob, Stephan M., Kim, Hyung-Sook, Levkovich, Bianca J., Lim, Sung Yoon, McGuinness, Shay, Parke, Rachael, Pellegrino, Vincent, Que, Yok-Ai, Reynolds, Claire, Rudham, Sam, Wallis, Steven C., Welch, Susan A., Zacharias, David, Fraser, John F., Shekar, Kiran, Roberts, Jason A. and on behalf of ASAP ECMO Investigators (2022). Population pharmacokinetics of vancomycin in critically ill adult patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study). Antimicrobial Agents and Chemotherapy, 66 (1) AAC0137721, 1-10. doi: 10.1128/aac.01377-21
Selby, Philip R., Warner, Morgyn S., Peake, Sandra L., Bardy, Peter, Hiwase, Devendra, Singhal, Deepak, Beligaswatte, Ashanka, Hahn, Uwe, Roberts, Jason A., Yeung, David and Shakib, Sepehr (2022). Optimizing antifungal prophylaxis in allogeneic stem cell transplantation: A cohort study of two different approaches. Transplant Infectious Disease, 24 (6) e13988, 1-11. doi: 10.1111/tid.13988
Cheng, Vesa, Abdul-Aziz, Mohd H., Burrows, Fay, Buscher, Hergen, Cho, Young-Jae, Corley, Amanda, Gilder, Eileen, Kim, Hyung-Sook, Lim, Sung Yoon, McGuinness, Shay, Parke, Rachael, Reynolds, Claire, Rudham, Sam, Wallis, Steven C., Welch, Susan A., Fraser, John F., Shekar, Kiran, Roberts, Jason A. and ASAP ECMO Investigators (2022). Population pharmacokinetics and dosing simulations of ceftriaxone in critically ill patients receiving extracorporeal membrane oxygenation (An ASAP ECMO Study). Clinical Pharmacokinetics, 61 (6), 847-856. doi: 10.1007/s40262-021-01106-x
Truong, Anh Quan, Dao, Xuan Co, Vu, Dinh Hoa, Nguyen, Hoang Anh, Do, Thi Hong Gam, Tran, Nhan Thang, Tran, Nhat Minh, Vu, Ngan Binh, Pham, Hong Nhung, Bui, Van Cuong, Trinh, The Anh, Dang, Quoc Tuan, Nguyen, Gia Binh, Lipman, Jeffrey, Cotta, Menino O. and Roberts, Jason A. (2022). Optimizing meropenem in highly resistant Klebsiella pneumoniae environments: population pharmacokinetics and dosing simulations in critically ill patients. Antimicrobial Agents and Chemotherapy, 66 (11) e0032122, 1-11. doi: 10.1128/aac.00321-22
Ling, Lowell, Mui, Oliver Oi Yat, Laupland, Kevin B., Lefrant, Jean-Yves, Roberts, Jason A., Gopalan, Pragasan Dean, Lipman, Jeffrey, Joynt, Gavin M., Stelfox, Tom, Niven, Daniel, Paramalingam, Rameiya, Vonderhaar, Derek, Freebairn, Ross, Ling, Lowell, Leung, Patricia, Gopalan, Dean, Lefrant, Jean Yves, Lloret, Sophie, Elotmani, Loubna, Fourie, Cheryl, Saba, Renee, Carlisle, Dougal and Edwards, Felicity (2022). Scoping review on diagnostic criteria and investigative approach in sepsis of unknown origin in critically ill patients. Journal of Intensive Care, 10 (1) 44, 1-10. doi: 10.1186/s40560-022-00633-4
Chau, Maggie M., Daveson, Kathryn, Alffenaar, Jan-Willem C., Gwee, Amanda, Ho, Su Ann, Marriott, Deborah J. E., Trubiano, Jason A., Zhao, Jessie, Roberts, Jason A., Chang, Christina C, Blyth, Christopher C, Chen, Sharon C-A, Khanina, Anna, Morrissey, C. Orla, Thursky, Karin A, Worth, Leon and Slavin, Monica A (2021). Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021. Internal Medicine Journal, 51 (S7), 37-66. doi: 10.1111/imj.15587
Barreto, Erin F., Rule, Andrew D., Alshaer, Mohammad H., Roberts, Jason A., Abdul Aziz, Mohd Hafiz, Scheetz, Marc H., Mara, Kristin C., Jannetto, Paul J., Gajic, Ognjen, O'Horo, John C and Boehmer, Kasey R (2021). Provider perspectives on beta-lactam therapeutic drug monitoring programs in the critically ill: a protocol for a multicenter mixed-methods study. Implementation science communications, 2 (1) 34, 34. doi: 10.1186/s43058-021-00134-9
An international survey on aminoglycoside practices in critically ill patients: the AMINO III study
Roger, Claire, Louart, Benjamin, Elotmani, Loubna, Barton, Greg, Escobar, Leslie, Koulenti, Despoina, Lipman, Jeffrey, Leone, Marc, Muller, Laurent, Boutin, Caroline, Amour, Julien, Banakh, Iouri, Cousson, Joel, Bourenne, Jeremy, Constantin, Jean-Michel, Albanese, Jacques, Roberts, Jason A., Lefrant, Jean-Yves, Darchy, Bruno, Sigismond, Lasocki, Debbat, Karim, Moschietto, Sébastien, Capellier, Gilles, Biais, Matthieu, Brunin, Guillaume, Huet, Olivier, Hausermann, Marie-Hélène, Just, Bernard, Constantin, Jean-Michel ... Felton, Timothy (2021). An international survey on aminoglycoside practices in critically ill patients: the AMINO III study. Annals of Intensive Care, 11 (1) 49, 49. doi: 10.1186/s13613-021-00834-4
Cheng, Vesa, Abdul-Aziz, Mohd H., Burrows, Fay, Buscher, Hergen, Corley, Amanda, Diehl, Arne, Jakob, Stephan M., Levkovich, Bianca J., Pellegrino, Vincent, Que, Yok-Ai, Reynolds, Claire, Rudham, Sam, Wallis, Steven C., Welch, Susan A., Zacharias, David, Roberts, Jason A., Shekar, Kiran, Fraser, John F. and on behalf ofASAP ECMO Investigators (2021). Population pharmacokinetics of cefepime in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study). International Journal of Antimicrobial Agents, 58 (6) 106466, 1-8. doi: 10.1016/j.ijantimicag.2021.106466
Ho, Su Ann, Slavin, Monica, Roberts, Jason A. and Yong, Michelle (2020). Optimization of Ganciclovir use in allogeneic hematopoietic cell transplant recipients – the role of therapeutic drug monitoring. Expert Review of Anti-infective Therapy, 19 (6), 1-12. doi: 10.1080/14787210.2021.1851193
Wong, Gloria, Briscoe, Scott, McWhinney, Brett, Ally, Mumtaz, Ungerer, Jacobus, Lipman, Jeffrey and Roberts, Jason A (2018) Therapeutic drug monitoring of β-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures. Journal of Antimicrobial Chemotherapy, . doi:10.1093/jac/dky314
Heil, Emily L., Nicolau, David P., Farkas, Andras, Roberts, Jason A. and Thom, Kerri A. (2018) Pharmacodynamic target attainment for cefepime, meropenem and piperacillin/tazobactam using a pharmacokinetic/pharmacodynamic-based dosing calculator in critically ill patients. Antimicrobial Agents and Chemotherapy, . doi:10.1128/AAC.01008-18
Abdul-Aziz, Mohd H., Driver, Elicia, Lipman, Jeffrey and Roberts, Jason A. (2018) New paradigm for rapid achievement of appropriate therapy in special populations: coupling antibiotic dose optimisation rapid microbiological methods. Expert Opinion on Drug Metabolism and Toxicology, 14 7: 1-16. doi:10.1080/17425255.2018.1484452
Minichmayr, Iris K., Roberts, Jason A., Frey, Otto R., Roehr, Anka C., Kloft, Charlotte and Brinkmann, Alexander (2018) Development of a dosing nomogram for continuous-infusion meropenem in critically ill patients based on a validated population pharmacokinetic model. The Journal of Antimicrobial Chemotherapy, 73 5: 1330-1339. doi:10.1093/jac/dkx526
