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

: Invasive fungal infections (IFI) are a major cause of morbidity and mortality in patients treated for acute S393 myeloid leukemia (AML) or those receiving allogeneic stem cell transplant (SCT). The interest of IFI prophylaxis by posaconazole (PCZ), an anti-fungal molecule with intramembrane mechanism of action, in these settings is well proved. Despite the threshold of 0.7 mg/l considered to the goal in prophylaxis indication, usefulness of therapeutic drug monitoring (TDM) of PCZ is still questionable because both poor plasma levels reached in practice and the absence of demonstrated correlation between blood and membrane levels. We evaluate the interest of the dosage of different sub-fractions of posaconazole and correlate them with confusion parameters known to influence results of PCZ monitoring. Material (or patients) and methods: Samples from the TDM of PCZ (oral suspension) performed in hematological malignancies between January and April 2015 in our laboratory were prospectively collected. In more, we measured the total fraction (TF) after hydrolysis of the glucuroconjugate, and the fraction in erythrocyte membrane (EF) of PCZ. We calculated the conjugated 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 blood cell count, glomerular filtration rate (GFR), albumin, intake of proton pump inhibitors, immunosuppressive drugs (IS), and corticosteroids.