Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper

Mohd H Abdul-Aziz, Jan-Willem C Alffenaar, Matteo Bassetti, Hendrik Bracht, George Dimopoulos, Deborah Marriott, Michael N Neely, Jose-Artur Paiva, Federico Pea, Fredrik Sjovall, Jean F Timsit, Andrew A Udy, Sebastian G Wicha, Markus Zeitlinger, Jan J De Waele, Jason A Roberts, Infection Section of European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Group of International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC), Mohd H Abdul-Aziz, Jan-Willem C Alffenaar, Matteo Bassetti, Hendrik Bracht, George Dimopoulos, Deborah Marriott, Michael N Neely, Jose-Artur Paiva, Federico Pea, Fredrik Sjovall, Jean F Timsit, Andrew A Udy, Sebastian G Wicha, Markus Zeitlinger, Jan J De Waele, Jason A Roberts, Infection Section of European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Group of International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), Infections in the ICU and Sepsis Working Group of International Society of Antimicrobial Chemotherapy (ISAC)

Abstract

Purpose: This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients.

Methods: Literature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes.

Results: TDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients.

Conclusion: Although TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide.

Keywords: Antibacterials; Antifungals; Antivirals; Pharmacodynamics; Pharmacokinetics; Sepsis.

Conflict of interest statement

Mohd H. Abdul-Aziz, Jan-Willem C. Alffenaar, Matteo Bassetti, Hendrik Bracht, George Dimopoulos, Deborah Marriott, Michael Neely, Jose-Artur Paiva, Fredrik Sjovall, Sebastian G. Wicha and Markus Zeitlinger declare no conflict of interest. Federico Pea participated in speaker bureau for Angelini, Basilea Pharmaceutica, Gilead, Hikma, Merck Sharp & Dohme, Nordic Pharma, Pfizer and Sanofi Aventis and in advisory board for Angelini, Basilea Pharmaceutica, Correvio, Gilead, Merck Sharp & Dohme, Nordic Pharma, Novartis, Pfizer and Thermo-Fisher. Jean F. Timsit has contributed to Medical Advisory Boards for Gilead Sciences, Inc., Merck Sharp & Dohme, MedImmune, Paratek Pharmaceuticals, Pfizer Inc. and Venatorx Pharmaceuticals, Inc. Jean F. Timsit has received research grants and/or lecture fees from Biomerieux, Gilead Sciences, Inc., Merck Sharp & Dohme and Pfizer Inc. Andrew A. Udy has contributed to Medical Advisory Boards for Baxter Healthcare Pty Ltd, Merck Sharp & Dohme (Australia) Pty Ltd, in addition to previously receiving honorarium and travel support from Pfizer Australia Pty Ltd. Jan J. De Waele has received consultation fees for Accelerate Diagnostics, Inc., Bayer Healthcare, Cubist Pharmaceuticals, Grifols, Merck Sharp & Dohme and Pfizer Inc. Jan J. De Waele is supported by a grant from the Research Foundation Flanders (Senior Clinical Investigator Grant FWO, Ref. 1881020 N). Jason A. Roberts receives funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452) and a Practitioner Fellowship (APP1117065).

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