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The efficacy of voriconazole in the treatment of 192 fungal central nervous system infections: a retrospective analysis

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Abstract

Purpose

The efficacy of voriconazole against fungal central nervous system (CNS) infections was examined retrospectively.

Methods

Voriconazole-treated patients with proven (137) or probable (55) CNS infections were identified in the voriconazole database (114) and the literature (78). Investigator-determined success was a complete or partial response. Survival was calculated from the start of voriconazole therapy.

Results

The patients’ age range was <1–81 years (median 43) and 127 (66%) were male. Aspergillus spp. (63%) and Scedosporium spp. (18%) predominated, but 12 other genera were recorded. Underlying conditions were haematopoietic stem cell transplantation (HSCT, 35), haematologic malignancy (HM, 35), solid-organ transplantation (SOT, 25), chronic immunosuppression (CI, 40) and other conditions (OC, 57). The median voriconazole therapy duration was 93 days (range 1–1,128), with success in 93 patients (48%). Only 35 patients received primary therapy, with success in 63% versus 45% for salvage (p = 0.06 NS). Underlying conditions influenced success; HSCT 14%, HM 54%, SOT 40%, CI 45% and OC 72% (p < 0.001). Additional antifungal combination therapy (37 patients) gave a trend towards an improved response rate (p = 0.09) and superior survival (p = 0.0149), while patients receiving neurosurgical interventions (72) showed superior responses (p = 0.0174) and survival (p = 0.0399). In all, 49% of patients died, 71% (67/94) due to fungal infection. The overall median survival was 297 days (range 3 to >2,000). Paediatric (p = 0.014) and literature patients (p < 0.001) exhibited superior survival compared with adults and voriconazole database patients, respectively.

Conclusions

Voriconazole shows encouraging efficacy against various CNS fungal infections. Combination therapy and/or CNS surgery may improve outcomes.

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Acknowledgments

We would like to thank Dr. Dieter Buchheidt (Germany), Dr. Eric Denes (France), Dr. Mareva Giacchino (Italy), Dr. Margit Hummel (Germany), Dr. Angie Pinto (Australia), Dr. Andrew J. Pollard (United Kingdom), Dr. Silke Schelenz (United Kingdom), Dr. Harman Singh (USA) and Dr. Nina Singh (USA) for providing the additional antifungal and survival data on their published cases. Some of the data included in this analysis were derived from Pfizer-sponsored studies. All data for the voriconazole database cases were supplied by Pfizer, according to S.S.’s and P.F.T.’s specifications, and decisions on the content of and the conclusions given in the manuscript were independently made by the authors.

Conflict of interest

This work was supported by Pfizer (financial support to P.F.T. for data analysis and towards the writing of this manuscript). S.S. has received travel grants and speaker honoraria from Astellas, Enzon and Pfizer. A.R. is an employee of Pfizer. P.F.T. was previously an employee of and is currently a consultant to Pfizer.

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  1. Medizinische Klinik III, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    S. Schwartz

  2. Pfizer Inc., New York, USA

    A. Reisman

  3. The Old Court, Broadstairs, UK

    P. F. Troke

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Schwartz, S., Reisman, A. & Troke, P.F. The efficacy of voriconazole in the treatment of 192 fungal central nervous system infections: a retrospective analysis. Infection 39, 201–210 (2011). https://doi.org/10.1007/s15010-011-0108-6

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