title: Risk factors for breakthrough invasive fungal infection during secondary prophylaxis.
abstract: BACKGROUND
  Intensive chemotherapy with severe neutropenia is associated with invasive fungal infections (IFIs) leading to high mortality rates. During leukaemia induction chemotherapy, IFI often prohibited further curative treatment, thus predisposing for leukaemia relapse. Continuing myelosuppressive chemotherapy after diagnosis of IFI has become feasible with the now expanding arsenal of safe and effective antifungals. Secondary prophylaxis of IFI is widely administered, but reliable data on outcome and risk factors for recurrent IFI during subsequent chemotherapy are not available. This study determines risk factors for recurrent IFI in leukaemia patients.
  
  
  METHODS
  From 25 European cancer centres, 166 consecutive patients with acute myelogenous leukaemia (AML) and a recent history of proven or probable pulmonary IFI were included. Patients were followed for recurrence or breakthrough IFI during the subsequent chemotherapy cycle.
  
  
  RESULTS
  Of the 166 patients included, 69 (41.6%) were female, the median age was 53 years (range 2-81) the and 3 (1.8%) were <16 years. Recurrent IFI occurred in 26 patients (15.7%). Multiple logistic regressions yielded predisposing factors: duration of neutropenia [per additional day; odds ratio (OR) 1.043, confidence interval (CI) 1.008-1.078], high-dose cytarabine (OR 3.920, CI 1.120-12.706), number of antibiotics (per antibiotic; OR 1.504, CI 1.089-2.086), partial response as outcome of prior IFI (OR 4.037, CI 1.301-12.524) and newly diagnosed AML (OR 3.823, CI 0.953-15.340). Usage of high efficiency particulate air filter appeared protective (OR 0.198, CI 0.036-1.089).
  
  
  CONCLUSIONS
  Duration of neutropenia, high-dose cytarabine, prior antibiotic therapy and a partial response to the first IFI therapy were risk factors for recurrent IFI and should be considered in AML patients with prior pulmonary IFI undergoing further chemotherapy.
authors.affiliation: Klinik I für Innere Medizin, Klinikum der Universität Köln, 50924 Köln, Germany. oliver.cornely@ctuc.de
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.forename: Angelika
authors.initials: A
authors.lastname: Böhme
authors.forename: Dietmar
authors.initials: D
authors.lastname: Reichert
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
authors.forename: Georg
authors.initials: G
authors.lastname: Maschmeyer
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Dieter
authors.initials: D
authors.lastname: Buchheidt
authors.forename: Monika
authors.initials: M
authors.lastname: Paluszewska
authors.forename: Dorothee
authors.initials: D
authors.lastname: Arenz
authors.forename: Ullrich
authors.initials: U
authors.lastname: Bethe
authors.forename: Jenny
authors.initials: J
authors.lastname: Effelsberg
authors.forename: Harry
authors.initials: H
authors.lastname: Lövenich
authors.forename: Michal
authors.initials: M
authors.lastname: Sieniawski
authors.forename: Antje
authors.initials: A
authors.lastname: Haas
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Hartmut
authors.initials: H
authors.lastname: Eimermacher
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: Gerda
authors.initials: G
authors.lastname: Silling
authors.forename: Moritz
authors.initials: M
authors.lastname: Hahn
authors.forename: Sidonie
authors.initials: S
authors.lastname: Wacker
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
authors.forename: Meinolf
authors.initials: M
authors.lastname: Karthaus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D018890:Chemoprevention; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000453:epidemiology* / Q000517:prevention & control*; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents