Therapeutic Drug Monitoring

Therapeutic Drug Monitoring Group

The Therapeutic Drug Monitoring Group (TDMG) aims to robustly identify antimicrobial pharmacokinetic-pharmacodynamic (PK-PD) targets for use in clinical practice by better defining relationships between antimicrobial blood concentrations and outcomes. Using defined antimicrobial PK-PD targets, the Group seeks to test innovative and advanced approaches for dose optimisation, such as using software-guided dosing, so that these can be maximised to help improve patient outcomes and reduce the emergence of antimicrobial resistance.

This research is coordinated by an interdisciplinary team at CRE REDUCE with strong national and international collaborations. There is a large focus of this research in translating findings into clinical practice and a number of workshops on antimicrobial dose optimisation are conducted by CRE REDUCE including the upcoming Antimicrobial Population PK/PD Modelling and Dose Optimisation workshop to be held July 2019 in Nîmes, Southern France.

Leading this team are Dr Menino Osbert Cotta (Team Leader) and Prof Jason Roberts.

Relevant Publications

1. Dhaese SAM, Farkas A, Colin P, Lipman J, Stove V, Verstraete AG, Roberts JA, De Waele JJ. Population pharmacokinetics and evaluation of the predictive performance of pharmacokinetic models in critically ill patients receiving continuous infusion meropenem: a comparison of eight pharmacokinetic models. J Antimicrob Chemother. 2019 Feb 1;74(2):432-441. doi: 10.1093/jac/dky434. PubMed PMID: 30376103

2. Wong G, Briscoe S, McWhinney B, Ally M, Ungerer J, Lipman J, Roberts JA. Therapeutic drug monitoring of β-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures. J Antimicrob Chemother. 2018 Nov 1;73(11):3087-3094. doi: 10.1093/jac/dky314. PubMed PMID: 30137377

3. Tängdén T, Cojutti PG, Roberts JA, Pea F. Valganciclovir Pharmacokinetics in Patients Receiving Oral Prophylaxis Following Kidney Transplantation and Model-Based Predictions of Optimal Dosing Regimens. Clin Pharmacokinet. 2018 Nov; 57(11):1399-1405. doi: 10.1007/s40262-018-0638-5. PubMed PMID: 29546589

4. Rawson TM, O'Hare D, Herrero P, Sharma S, Moore LSP, de Barra E, Roberts JA, Gordon AC, Hope W, Georgiou P, Cass AEG, Holmes AH Delivering precision antimicrobial therapy through closed-loop control systems. J Antimicrob Chemother. 2018 Apr 1;73(4):835-843. doi: 10.1093/jac/dkx458

5. Heil, Emily L., Nicolau, David P., Farkas, Andras, Roberts, Jason A. and Thom, Kerri A. Pharmacodynamic target attainment for cefepime, meropenem and piperacillin/tazobactam using a pharmacokinetic/pharmacodynamic-based dosing calculator in critically ill patients. Antimicrobial Agents and Chemotherapy, (2018), doi:10.1128/AAC.01008-18

6. Minichmayr, Iris K., Roberts, Jason A., Frey, Otto R., Roehr, Anka C., Kloft, Charlotte and Brinkmann, A. 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, (2018), 73 5: 1330-1339. doi:10.1093/jac/dkx526

7. Roger, C., Roberts, J. A., & Muller, L. (2018). Clinical pharmacokinetics and pharmacodynamics of oxazolidinones. Clinical pharmacokinetics, 57(5), 559-575

8. Kumta, N., Roberts, J. A., Lipman, J., & Cotta, M. O. (2018). Antibiotic distribution into cerebrospinal fluid: can dosing safely account for drug and disease factors in the treatment of ventriculostomy-associated infections?. Clinical pharmacokinetics, 57(4), 439-454

9. Tängdén T, Ramos Martín V, Felton TW, Nielsen EI, Marchand S, Brüggemann RJ, Bulitta JB, Bassetti M, Theuretzbacher U, Tsuji BT, Wareham DW, Friberg LE, De Waele JJ, Tam VH, Roberts JA; Infection Section for the European Society of Intensive Care Medicine, the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases, the International Society of Anti-Infective Pharmacology and the Critically Ill Patients Study Group of European Society of Clinical Microbiology and Infectious Diseases. The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections. Intensive Care Med. 2017 Jul;43(7):1021-1032. doi: 10.1007/s00134-017-4780-6. Epub 2017 Apr 13. Review. PubMed PMID: 28409203

10. Economou CJP, Wong G, McWhinney B, Ungerer JPJ, Lipman J, Roberts JA. Impact of β-lactam antibiotic therapeutic drug monitoring on dose adjustments in critically ill patients undergoing continuous renal replacement therapy. Int J Antimicrob Agents. 2017 May;49(5):589-594. doi: 10.1016/j.ijantimicag.2017.01.009. Epub 2017 Mar 21. PubMed PMID: 28341612

11. Jager NG, van Hest RM, Lipman J, Taccone FS, Roberts JA Therapeutic drug monitoring of anti-infective agents in critically ill patients. Expert Rev Clin Pharmacol. 2016 Jul;9(7):961-79. doi: 10.1586/17512433.2016.1172209. Epub 2016 Apr 15.

12. Farkas, A., Daroczi, G., Villasurda, P., Dolton, M., Nakagaki, M., & Roberts, J. A. (2016). Comparative evaluation of the predictive performance of three different structural population pharmacokinetic models to predict future voriconazole concentrations. Antimicrobial agents and chemotherapy, AAC-00970

13. Roger, C., Wallis, S. C., Louart, B., Lefrant, J. Y., Lipman, J., Muller, L., & Roberts, J. A. (2016). Comparison of equal doses of continuous venovenous haemofiltration and haemodiafiltration on ciprofloxacin population pharmacokinetics in critically ill patients. Journal of Antimicrobial Chemotherapy, 71(6), 1643-1650

14. Cotta, M. O., Roberts, J. A., & Lipman, J. (2016). We need to optimize piperacillin-tazobactam dosing in critically ill patients—but how?. Critical Care, 20(1), 163

15. McDonald, C., Cotta, M. O., Little, P. J., Mcwhinney, B., Ungerer, J. P., Lipman, J., & Roberts, J. A. (2016). Is high-dose β-lactam therapy associated with excessive drug toxicity in critically ill patients?. Minerva anestesiologica, 82(9), 957-965