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Limited penetration of posaconazole into cerebrospinal fluid in an allogeneic stem cell recipient with invasive pulmonary aspergillosis

Bone Marrow Transplantation volume 44, pages 269–270 (2009)Cite this article

Invasive mold infections are a potentially lethal complication in patients receiving allogeneic hematopoietic SCT (alloHSCT) and have a major impact on morbidity and mortality. Cumulative incidences of invasive aspergillosis range up to 7% in patients with alloHSCT.1 Cerebral aspergillosis carries particularly a poor prognosis. In a recent analysis of patients with invasive aspergillosis after alloHSCT, 14 (42%) of 33 patients had central nervous system (CNS) involvement. None of these 14 patients with cerebral aspergillosis responded to amphotericin B therapy and all patients experienced rapid deterioration. The mortality was 100% and the median survival from the onset of symptoms or signs of cerebral aspergillosis was only 7 days.1 Penetration of amphotericin B, itraconazole and echinocandins into the CNS is low to negligible, whereas voriconazole penetrates well into the CNS.2, 3 In a recent retrospective analysis, improved response (35%) and survival (31%) rates were observed in 81 patients treated with voriconazole for cerebral aspergillosis.4

Posaconazole is a new triazole with broad activity against various fungi, including Aspergillus species and Zygomycetes, and has recently gained approval for antifungal prophylaxis in patients with alloHSCT and GVHD.5 In addition, posaconazole exhibits activity in various CNS fungal diseases, including cerebral zygomycosis.6 However, limited CNS pharmacokinetic data on posaconazole are available. Cerebrospinal fluid (CSF) concentrations of posaconazole were found to be less than 50 ng/ml in a rabbit model with cryptococcal meningitis.7 In a recent report, posaconazole CSF concentrations ranged from 153 to 221 ng/ml in two patients and were undetectable in another patient.8

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Authors and Affiliations

  1. Medizinische Klinik III, Charité Campus Benjamin Franklin, Berlin, Germany

    M Reinwald, L Uharek, E Thiel & S Schwartz

  2. Institut für Toxikologie, Berliner Betrieb für Zentrale Gesundheitliche Aufgaben, Berlin, Germany

    D Lampe & T Grobosch

Authors
  1. M Reinwald
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  2. L Uharek
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  3. D Lampe
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  4. T Grobosch
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  5. E Thiel
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  6. S Schwartz
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Correspondence to S Schwartz.

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Reinwald, M., Uharek, L., Lampe, D. et al. Limited penetration of posaconazole into cerebrospinal fluid in an allogeneic stem cell recipient with invasive pulmonary aspergillosis. Bone Marrow Transplant 44, 269–270 (2009). https://doi.org/10.1038/bmt.2009.17

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