title: The efficacy of voriconazole in the treatment of 192 fungal central nervous system infections: a retrospective analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Medizinische Klinik III, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany. stefan.schwartz@charite.de
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: A
authors.initials: A
authors.lastname: Reisman
authors.forename: P F
authors.initials: PF
authors.lastname: Troke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D001230:Aspergillus / Q000472:pathogenicity; D020314:Central Nervous System Fungal Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D021681:Scedosporium / Q000472:pathogenicity; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole