title: Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.
abstract: BACKGROUND
  Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients.
  
  
  METHODS
  Non-neutropenic patients with a positive blood culture for a species of candida and clinical evidence of infection were enrolled. Patients were randomly assigned, in a 2:1 ratio, either voriconazole (n=283) or amphotericin B followed by fluconazole (n=139). The primary efficacy analysis was based on clinical and mycological response 12 weeks after the end of treatment, assessed by an independent data-review committee unaware of treatment assignment.
  
  
  RESULTS
  Of 422 patients randomised, 370 were included in the modified intention-to-treat population. Voriconazole was non-inferior to amphotericin B/fluconazole in the primary efficacy analysis, with successful outcomes in 41% of patients in both treatment groups (95% CI for difference -10.6% to 10.6%). At the last evaluable assessment, outcome was successful in 162 (65%) patients assigned voriconazole and 87 (71%) assigned amphotericin B/fluconazole (p=0.25). Voriconazole cleared blood cultures as quickly as amphotericin B/fluconazole (median time to negative blood culture, 2.0 days). Treatment discontinuations due to all-cause adverse events were more frequent in the voriconazole group, although most discontinuations were due to non-drug-related events and there were significantly fewer serious adverse events and cases of renal toxicity than in the amphotericin B/fluconazole group.
  
  
  CONCLUSIONS
  Voriconazole was as effective as the regimen of amphotericin B followed by fluconazole in the treatment of candidaemia in non-neutropenic patients, and with fewer toxic effects.
  
  
  CONCLUSIONS
  There are several options for treatment of candidaemia in non-neutropenic patients, including amphotericin B, fluconazole, voriconazole, and echinocandins. Voriconazole can be given both as initial intravenous treatment and as an oral stepdown agent.
authors.affiliation: Nijmegen University Centre for Infectious Diseases, Department of Internal Medicine (484), Radboud University Nijmegen Medical Centre (541), PO Box 9101, 6500 HB Nijmegen, Netherlands. b.kullberg@aig.umcn.nl
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: J D
authors.initials: JD
authors.lastname: Sobel
authors.forename: M
authors.initials: M
authors.lastname: Ruhnke
authors.forename: P G
authors.initials: PG
authors.lastname: Pappas
authors.forename: C
authors.initials: C
authors.lastname: Viscoli
authors.forename: J H
authors.initials: JH
authors.lastname: Rex
authors.forename: J D
authors.initials: JD
authors.lastname: Cleary
authors.forename: E
authors.initials: E
authors.lastname: Rubinstein
authors.forename: L W P
authors.initials: LW
authors.lastname: Church
authors.forename: J M
authors.initials: JM
authors.lastname: Brown
authors.forename: H T
authors.initials: HT
authors.lastname: Schlamm
authors.forename: I T
authors.initials: IT
authors.lastname: Oborska
authors.forename: F
authors.initials: F
authors.lastname: Hilton
authors.forename: M R
authors.initials: MR
authors.lastname: Hodges
mesh_terms: D018806:APACHE; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000666:Amphotericin B / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002177:Candidiasis / Q000145:classification / Q000188:drug therapy* / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D000666:Amphotericin B; D015725:Fluconazole; D065819:Voriconazole