Is there an interest of new techniques for dosing posaconazole in invasive fungal infection prophylaxis?

Abstract

International audience: Invasive fungal infections (IFI) are a major causeof morbidity and mortality in patients treated for acuteS393myeloid leukemia (AML) or those receiving allogeneic stemcell transplant (SCT). The interest of IFI prophylaxis byposaconazole (PCZ), an anti-fungal molecule with intramembrane mechanism of action, in these settings is wellproved. Despite the threshold of 0.7 mg/l considered to thegoal in prophylaxis indication, usefulness of therapeutic drugmonitoring (TDM) of PCZ is still questionable because bothpoor plasma levels reached in practice and the absence ofdemonstrated correlation between blood and membranelevels. We evaluate the interest of the dosage of differentsub-fractions of posaconazole and correlate them withconfusion parameters known to influence results of PCZmonitoring.Material (or patients) and methods: Samples from the TDM ofPCZ (oral suspension) performed in hematological malignanciesbetween January and April 2015 in our laboratory wereprospectively collected. In more, we measured the total fraction(TF) after hydrolysis of the glucuroconjugate, and the fraction inerythrocyte membrane (EF) of PCZ. We calculated theconjugated fraction (GF = TF - UF) and the ratio of conjugation.Results were correlated with 13 confusion parameters: indication of prophylaxis, body-mass index and surface area, ethnicity,fever, nutrition mode, hemoglobin concentration, white bloodcell count, glomerular filtration rate (GFR), albumin, intake ofproton pump inhibitors, immunosuppressive drugs (IS), andcorticosteroids