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

Mohd H Abdul-Aziz¹, Jan-Willem C Alffenaar^{2

3

4}, Matteo Bassetti⁵, Hendrik Bracht⁶, George Dimopoulos⁷, Deborah Marriott⁸, Michael N Neely^{9

10}, Jose-Artur Paiva^{11

12}, Federico Pea¹³, Fredrik Sjovall¹⁴, Jean F Timsit^{15

16}, Andrew A Udy^{17

18}, Sebastian G Wicha¹⁹, Markus Zeitlinger²⁰, Jan J De Waele²¹, Jason A Roberts^{22

23

24

25}; 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)

Affiliations

¹ University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4029, Australia.
² School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³ Westmead Hospital, Westmead, NSW, Australia.
⁴ Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia.
⁵ Infectious Diseases Clinic, Department of Health Sciences, University of Genoa, Genoa and Hospital Policlinico San Martino - IRCCS, Genoa, Italy.
⁶ Department of Anaesthesiology, University Ulm, Ulm, Germany.
⁷ Department of Critical Care, University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece.
⁸ Department of Microbiology and Infectious Diseases, St. Vincent's Hospital, Sydney, NSW, Australia.
⁹ Department of Paediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁰ Division of Infectious Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Medicine, Faculty of Medicine of Porto, Porto, Portugal.
¹² Department of Emergency and Intensive Care Medicine, Centro Hospitalar Universitario de São João, Porto, Portugal.
¹³ Institute of Clinical Pharmacology, SM Misericordia University Hospital, ASUFC, Udine, Italy.
¹⁴ Department of Perioperative Medicine, Skåne University Hospital, Malmö, Sweden.
¹⁵ Department of Intensive Care Medicine and Infectious Diseases, Bichat-Claude Bernard University Hospital, AP-HP, Paris, France.
¹⁶ Infection, Antimicrobials, Modelling, Evolution (IAME), Paris Diderot University, Paris, France.
¹⁷ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
¹⁸ Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, VIC, Australia.
¹⁹ Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
²⁰ Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
²¹ Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium.
²² University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4029, Australia. j.roberts2@uq.edu.au.
²³ Department of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
²⁴ Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
²⁵ Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France. j.roberts2@uq.edu.au.

PMID: 32383061
PMCID: PMC7223855
DOI: 10.1007/s00134-020-06050-1

Review

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

Mohd H Abdul-Aziz et al. Intensive Care Med. 2020 Jun.

. 2020 Jun;46(6):1127-1153.

doi: 10.1007/s00134-020-06050-1. Epub 2020 May 7.

Authors

Affiliations

¹ University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4029, Australia.
² School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³ Westmead Hospital, Westmead, NSW, Australia.
⁴ Marie Bashir Institute of Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia.
⁵ Infectious Diseases Clinic, Department of Health Sciences, University of Genoa, Genoa and Hospital Policlinico San Martino - IRCCS, Genoa, Italy.
⁶ Department of Anaesthesiology, University Ulm, Ulm, Germany.
⁷ Department of Critical Care, University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece.
⁸ Department of Microbiology and Infectious Diseases, St. Vincent's Hospital, Sydney, NSW, Australia.
⁹ Department of Paediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁰ Division of Infectious Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
¹¹ Department of Medicine, Faculty of Medicine of Porto, Porto, Portugal.
¹² Department of Emergency and Intensive Care Medicine, Centro Hospitalar Universitario de São João, Porto, Portugal.
¹³ Institute of Clinical Pharmacology, SM Misericordia University Hospital, ASUFC, Udine, Italy.
¹⁴ Department of Perioperative Medicine, Skåne University Hospital, Malmö, Sweden.
¹⁵ Department of Intensive Care Medicine and Infectious Diseases, Bichat-Claude Bernard University Hospital, AP-HP, Paris, France.
¹⁶ Infection, Antimicrobials, Modelling, Evolution (IAME), Paris Diderot University, Paris, France.
¹⁷ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
¹⁸ Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, VIC, Australia.
¹⁹ Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
²⁰ Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
²¹ Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium.
²² University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4029, Australia. j.roberts2@uq.edu.au.
²³ Department of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
²⁴ Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. j.roberts2@uq.edu.au.
²⁵ Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France. j.roberts2@uq.edu.au.

PMID: 32383061
PMCID: PMC7223855
DOI: 10.1007/s00134-020-06050-1

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.

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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).

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical