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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2641-2645.
Prepublished online as a Blood First Edition Paper on July 5, 2005; DOI 10.1182/blood-2005-02-0733.
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CLINICAL TRIALS AND OBSERVATIONS
Improved outcome in central nervous system aspergillosis, using voriconazole treatment
Stefan Schwartz,
Markus Ruhnke,
Patricia Ribaud,
Lawrence Corey,
Timothy Driscoll,
Oliver A. Cornely,
Ulrich Schuler,
Irja Lutsar,
Peter Troke, and
Eckhard Thiel
From the Medizinische Klinik III, Charité Campus Benjamin Franklin, Freie Universität and the Medizinische Klinik und Poliklinik II, Charité Campus Mitte, Humboldt Universität, Berlin, Germany; the Hôpital Saint-Louis, Paris, France; the Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, WA; the Division of Hematology-Oncology, Duke University Medical Center, Durham, NC; the Klinik I für Innere Medizin, Klinikum der Universität zu Köln, Köln, Germany; the Medizinische Klinik I, Universitätsklinikum Carl-Gustav-Carus, Dresden, Germany; the Institute of Microbiology, University of Tartu, Tartu, Estonia; and Pfizer Global Research, Sandwich, United Kingdom.
The mortality of central nervous system (CNS) aspergillosis approaches 100%, requiring improved therapies. Voriconazole gives superior efficacy and survival in invasive aspergillosis, compared with amphotericin B. Also, in contrast to other antifungal drugs, voriconazole penetrates well into the CNS. We evaluated, retrospectively, the outcome and survival of 81 patients who were treated with voriconazole for definite (n = 48) or probable (n = 33) CNS aspergillosis. Complete and partial responses were recorded in 35% of patients and varied by the underlying disease group: hematologic malignancies (54%), other underlying conditions (50%), chronic immunosuppression (45%), solid organ transplantation (36%), and hematopoietic stem cell transplantation (16%). Thirty-one percent of patients survived CNS aspergillosis for a median observation time of 390 days. There were 31 patients who underwent neurosurgical procedures, including craniotomy/abscess resection (n = 14), abscess drainage (n = 12), ventricular shunt (n = 4), and Ommaya-reservoir (n = 1). Multifactorial analysis revealed that neurosurgery was associated with improved survival (P = .02). Patients who underwent hematopoietic stem cell transplantation had a poorer survival (P = .02), but 7 (22%) of 32 survived for a median of 203 days. We conclude from this large cohort of patients that voriconazole treatment together with neurosurgical management, whenever feasible, is currently the best approach to treat patients with CNS aspergillosis.

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