title: Posaconazole plasma concentrations and invasive mould infections in patients with haematological malignancies.
abstract: Posaconazole (PCZ) is a triazole antifungal agent that has broad activity against pathogenic fungi and is increasingly used for prophylaxis and treatment of invasive mould infections (IMIs). PCZ is only available as an oral formulation, with varying absorption from the gastrointestinal tract. However, reports correlating PCZ plasma concentrations (PPCs) with breakthrough IMIs are rare. In this study, PPCs were analysed in a prospective, observational, single-centre study and the correlation of PPCs with breakthrough IMIs in patients with haematological malignancies was evaluated. Risk factors associated with low PPCs were further evaluated. A total of 109 PPCs were measured in 34 cases receiving PCZ prophylaxis (n=31) or treatment (n=3). Levels below the target of 0.5 μg/mL were detected in 24 (71%) of the 34 cases; in 15 (63%) of these 24 cases concentrations were found to be <0.20 μg/mL. Three patients receiving PCZ prophylaxis met the criteria of breakthrough infection. Notably, prior to development of IMI, PPCs were below the target in all three individuals. Associated risk factors for insufficient PPCs varied from previous reports. In conclusion, these data demonstrate that therapeutic drug monitoring of PCZ is mandatory in all patients with haematological malignancies as low PPCs are common and may be associated with development of IMIs.
authors.affiliation: Section of Infectious Diseases, Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 20, 8036 Graz, Austria. martin.hoenigl@medunigraz.at
authors.forename: Martin
authors.initials: M
authors.lastname: Hoenigl
authors.forename: Reinhard B
authors.initials: RB
authors.lastname: Raggam
authors.forename: Helmut J F
authors.initials: HJ
authors.lastname: Salzer
authors.forename: Thomas
authors.initials: T
authors.lastname: Valentin
authors.forename: Angelika
authors.initials: A
authors.lastname: Valentin
authors.forename: Ines
authors.initials: I
authors.lastname: Zollner-Schwetz
authors.forename: Anna T
authors.initials: AT
authors.lastname: Strohmeier
authors.forename: Katharina
authors.initials: K
authors.lastname: Seeber
authors.forename: Albert
authors.initials: A
authors.lastname: Wölfler
authors.forename: Heinz
authors.initials: H
authors.lastname: Sill
authors.forename: Robert
authors.initials: R
authors.lastname: Krause
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy / Q000517:prevention & control; D018890:Chemoprevention; D016903:Drug Monitoring; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000097:blood / Q000188:drug therapy / Q000517:prevention & control*; D012307:Risk Factors; D014230:Triazoles / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole