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JAC Advance Access originally published online on February 12, 2008
Journal of Antimicrobial Chemotherapy 2008 61(4):939-946; doi:10.1093/jac/dkn027
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Risk factors for breakthrough invasive fungal infection during secondary prophylaxis

Oliver A. Cornely1,*, Angelika Böhme2, Dietmar Reichert3, Stefan Reuter4, Georg Maschmeyer5, Johan Maertens6, Dieter Buchheidt7, Monika Paluszewska8, Dorothee Arenz1, Ullrich Bethe1, Jenny Effelsberg1, Harry Lövenich1, Michal Sieniawski1, Antje Haas9, Hermann Einsele10, Hartmut Eimermacher11, Rodrigo Martino12, Gerda Silling13, Moritz Hahn14, Sidonie Wacker14, Andrew J. Ullmann15, Meinolf Karthaus on behalf of The Multinational Case Registry of the Infectious Diseases Working Party of the German Society for Hematology and Oncology16

1 Klinik I für Innere Medizin, Klinikum der Universität Köln, 50924 Köln, Germany 2 Johann Wolfgang Goethe-Universität Frankfurt am Main, Medizinische Klinik III, Theodor-Stern-Kai 7, 60590 Frankfurt a. M., Germany 3 Städtische Kliniken Oldenburg, Klinik für Innere Medizin II, Dr. Eden-Strasse 10, 26133 Oldenburg, Germany 4 Universitätsklinikum Ulm, Innere Medizin III, Robert-Koch-Str. 8, 89081 Ulm, Germany 5 Universitätsklinikum Charité Campus Virchow-Klinikum, Medizinische Klinik, Hämatologie und Onkologie, Augustenburger Platz 1, 13353 Berlin, Germany 6 Department of Haematology, Universitaire Ziekenhuizen Leuven, Herestraat 49, 3000 Leuven, Belgium 7 Universitätsklinikum Mannheim, Medizinische Klinik III, Wiesbadener Str. 7-11, 68305 Mannheim Germany 8 Department of Haematology, Oncology and Internal Diseases, Medical University of Warsaw, ul. Banacha 1a, 02097 Warsaw, Poland 9 Klinikum Ernst von Bergmann, Klinik für Hämatologie und Onkologie, Charlottenstrasse 72, 14467 Potsdam, Germany 10 Medizinische Klinik u. Poliklinik II der Julius-Maximilians-Universität Würzburg, Josef-Schneider-Strasse 6-8, 97070 Würzburg, Germany 11 St-Marien-Hospital, Medizinische Klinik II, Bergstr. 56, 58095 Hagen, Germany 12 Hospital de la Santa Creu i Sant Pau Barcelona, Division of Clinical Hematology, Autonomous University of Barcelona, Avenida Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain 13 Medizinische Klinik der WWU Münster, Innere Medizin A, KMT-Zentrum, Dormagkstrasse 9a, 48149 Münster, Germany 14 Institut für Medizinische Statistik, Informatik und Epidemiologie, Klinikum der Universität Köln, 50924 Köln, Germany 15 Johannes-Gutenberg-Universität Mainz, III. Medizinische Klinik, Langenbeckstrasse 1, 55101 Mainz, Germany 16 Ev. Johannes-Krankenhaus, Medizinische Klinik II, Hämatologie/Onkologie, Schildescher Strasse 99, 33611 Bielefeld, Germany

Received 1 June 2007; returned 17 August 2007; revised 7 January 2008; accepted 8 January 2008

* Corresponding author. Tel: +49-221-478-6494; Fax: +49-221-478-3611; E-mail: oliver.cornely{at}ctuc.de

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.

Keywords: antifungal prophylaxis , polyenes , triazoles , echinocandins


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