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

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