by Emmanuel Novy,
Claire Roger, Jason A. Roberts and Menino Osbert Cotta
Critical Care volume 27,
Article number: 449 (2023) Published: 20
November 2023
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.
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.
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