Pharmacokinetic and pharmacodynamic considerations for antifungal therapy optimisation in the treatment of intra-abdominal candidiasis

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Abstract

Intra-abdominal candidiasis (IAC) is one of the most common of invasive candidiasis observed in critically ill patients. It is associated with high mortality, with up to 50% of deaths attributable to delays in source control and/or the introduction of antifungal therapy. Currently, there is no comprehensive guidance on optimising antifungal dosing in the treatment of IAC among the critically ill. However, this form of abdominal sepsis presents specific pharmacokinetic (PK) alterations and pharmacodynamic (PD) challenges that risk suboptimal antifungal exposure at the site of infection in critically ill patients. This review aims to describe the peculiarities of IAC from both PK and PD perspectives, advocating an individualized approach to antifungal dosing. Additionally, all current PK/PD studies relating to IAC are reviewed in terms of strength and limitations, so that core elements for the basis of future research can be provided.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-023-04742-w.

Highlights

Intra-abdominal candidiasis presents specific pharmacokinetic (PK) and pharmacodynamic (PD) challenges where suboptimal antifungal concentrations are likely to occur leading to high risk of treatment failure.
The intra-abdominal cavity has been highlighted as a hidden reservoir for resistance to antifungals including echinocandins.
To date, all antifungal PK/PD studies in intra-abdominal candidiasis have enrolled small cohorts and have only provided post-operative antifungal concentrations analysis.
Based on current evidence, high dosing regimens of antifungals should be strongly considered, especially at the onset of infection.
The place of new antifungals (rezafungin, ibrexafungerp) requires more robust clinical studies including PK/PD analysis in critically ill patients.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13054-023-04742-w.

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Most cited references 153

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Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

Peter Pappas, Carol A Kauffman, David Andes … (2015)

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

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Invasive Candidiasis.

Bart Kullberg, Maiken C. Arendrup (2015)

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

Mohd H Abdul-Aziz, Jan-Willem C. Alffenaar, Matteo Bassetti … (2020)

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. Electronic supplementary material The online version of this article (10.1007/s00134-020-06050-1) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Jason A. Roberts: j.roberts2@uq.edu.au

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 20 November 2023

Publication date PMC-release: 20 November 2023

Publication date Collection: 2023

Volume: 27

Electronic Location Identifier: 449

Affiliations

[1 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, , The University of Queensland, Royal Brisbane & Women’s Hospital Campus Herston, ; Brisbane, QLD 4029 Australia

[2 ]Department of Anaesthesiology, Critical Care and Peri-Operative Medicine, University Hospital of Nancy, ( https://ror.org/016ncsr12) Nancy, France

[3 ]GRID grid.29172.3f, ISNI 0000 0001 2194 6418, Université de Lorraine, SIMPA, ; 54500 Nancy, France

[4 ]GRID grid.411165.6, ISNI 0000 0004 0593 8241, Department of Anesthesiology, Critical Care, Pain and Emergency Medicine, , Nimes University Hospital, ; Place du Professeur Robert Debré, 30029 Nîmes Cedex 9, France

[5 ]GRID grid.121334.6, ISNI 0000 0001 2097 0141, UR UM103 IMAGINE, , Univ Montpellier, ; Montpellier, France

[6 ]Department of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women’s Hospital, ( https://ror.org/05p52kj31) Brisbane, QLD Australia

[7 ]GRID grid.518311.f, ISNI 0000 0004 0408 4408, Herston Infectious Diseases Institute (HeIDI), Metro North Health, ; Brisbane, Australia

Article

Publisher ID: 4742

DOI: 10.1186/s13054-023-04742-w

PMC ID: 10659066

PubMed ID: 37981676

SO-VID: 50f19054-6bc7-43b9-bb17-e7688890a7ec

License:

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