title: Outcome of empirical or targeted antifungal therapy after antifungal prophylaxis in febrile neutropenia.
abstract: Azole prophylaxis has been shown to be effective in preventing invasive fungal infections (IFIs) and increasing survival in patients with prolonged neutropenia after myelosuppressive chemotherapy for haematological malignancies. Similarly, empirical antifungal therapy for persistent neutropenic fever has been shown to reduce IFI-related mortality. However, to date, there is little information with regard to the outcome of patients who receive both strategies. Here, we present our retrospective data on three cohorts of patients receiving empirical or targeted antifungal therapy after different antifungal prophylaxis regimens. All records from patients who received myelosuppressive induction chemotherapy for acute myelogenous leukemia (AML) in our centre from 2004-2010 were analysed. From 2004-2006, itraconazole was used as antifungal prophylaxis; for the first 6 months in 2007, local polyenes and from mid-2007 till 2010, posaconazole. Data of 315 courses of chemotherapy in 211 patients were analysed. Antifungal therapy (empirical or targeted, time point and antifungal agent at the physician's discretion) was initiated in 50/174 (29 %), 7/18 (39 %) and 34/123 courses (28 %, p = 0.615) in the itra cohort, the cohort without systemic prophylaxis and the posa cohort, respectively, and was effective in 24/50 (48 %), 5/7 (71 %) and 22/34 courses (65 %, p = 0.221), respectively. IFI occurred in 25/174 (14 %), 4/18 (22 %) and 16/123 (13 %) courses, respectively (p = 0.580). IFI-related survival was not different in the three cohorts. Antifungal treatment in patients with AML who received azole prophylaxis resulted in the expected efficacy-importantly, prior posaconazole prophylaxis did not render subsequent antifungal treatment less effective than prior itraconazole prophylaxis.
authors.affiliation: Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany. corinna.hahn-ast@ukb.uni-bonn.de.
authors.forename: C
authors.initials: C
authors.lastname: Hahn-Ast
authors.affiliation: Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Felder
authors.affiliation: Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Mayer
authors.affiliation: Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Mückter
authors.affiliation: Paracelsus-Klinik Osnabrück, Osnabrück, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ruhnke
authors.affiliation: Institut für Medizinische Statistik, Informatik und Epidemiologie, Universität zu Köln, Köln, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hein
authors.affiliation: Institut für Medizinische Statistik, Informatik und Epidemiologie, Universität zu Köln, Köln, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hellmich
authors.affiliation: Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schwab
authors.affiliation: Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Rachow
authors.affiliation: Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Brossart
authors.affiliation: Medizinische Klinik und Poliklinik III, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.|Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Germany.|Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e.V., Hans-Knöll-Institut, Jena, Germany.|Center for Sepsis Control and Care (CSCC), Universitätsklinikum Jena, Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Lilienfeld-Toal
mesh_terms: D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D016503:Drug Delivery Systems / Q000379:methods*; D036262:Empirical Research; D064147:Febrile Neutropenia / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D056990:Post-Exposure Prophylaxis / Q000379:methods; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole
keywords: Antifungal prophylaxis; Antimycotic chemotherapy; Empirical antifungal therapy; Febrile neutropenia; Invasive fungal infections