Screening Anti-Fungal Exposure in Intensive Care Units

Adequate antifungal therapy is a critical determinant of survival in patients admitted to an
Intensive Care Unit (ICU) with suspected or proven fungal infections. Critical illness can
alter the way human body handles antifungal agents, i.e. how the drugs are distributed in the
body and removed from the body. Consequently, these changes can increase the risk of
inappropriate antifungal exposure that may lead to adverse consequence on patients' outcome.
Developing an evidence-based antifungal dosing guideline is of global significance and should
be considered a priority to improving clinical outcomes for patients receiving antifungal
agents

The aim of the SAFE-ICU Study is to develop optimised antibiotic dosing guidelines for ICU
patients with life-threatening infections that account for patient characteristics. This will
be achieved through completion of the following aims:

i) Describe detailed demographic, clinical and plasma antibiotic concentration-time data in a
large ICU patient cohort; ii) Perform a robust statistical analysis of the data collected in
Aim 1 to develop an enhanced preliminary prediction algorithm for antifungal dosing.

This is a multi-national study and will enrol ICU patients who are prescribed an antifungal
agent (fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, anidulafungin,
micafungin or amphotericin B). A minimum of 12 patients per drug will be enrolled across at
least 15 countries and up to 80 ICUs.

Eligible patients are those admitted to the ICU, who are prescribed an antifungal agent
(fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, anidulafungin,
micafungin or amphotericin B). Blood samples will be taken to measure drug concentration.
Sampling will occur on two occasions, first during study days 1-3 and then a second time
between days 4-7, each over an 8-24 hour period. Blood samples will be taken from a vascular
access device already inserted for ICU patient care. Abdominal samples from abdominal
indwelling drains already inserted peri operatively will also be collected on these two
occasions in the subgroup of patients with intra-abdominal infection. Data on infection,
various blood tests and patient specific data will be collected using a structured case
report form (CRF). Patients will also be followed up 30 days after enrolment into the study
to evaluate 30-day mortality.

Collected samples will be frozen and stored locally and then shipped in large batches for
processing at Burns Trauma and Critical Care Research Centre, The University of Queensland,
Australia. Data analysis for development of antifungal dosing algorithms will also be
undertaken at The University of Queensland, Australia.