title: Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome.
abstract: BACKGROUND
  In a previous randomized trial of voriconazole versus amphotericin B deoxycholate for primary therapy of invasive aspergillosis, voriconazole demonstrated superior efficacy and better survival. In that trial, treatment with voriconazole or amphotericin B deoxycholate could be followed with other licensed antifungal therapies (OLAT). Here, we report the impact of OLAT on the outcome of patients with invasive aspergillosis.
  
  
  METHODS
  Data on dose, duration, and the reason for switching to the first OLAT were analyzed, and outcome at week 12 was assessed.
  
  
  RESULTS
  Fewer patients in the voriconazole group (52 [36%] of 144) switched to OLAT, compared with patients in the amphotericin B deoxycholate group (107 [80%] of 133). Lipid formulations of amphotericin B were the most common OLAT (38% of patients). Switches were made because of intolerance or insufficient response in 70% for patients in the amphotericin B deoxycholate group, compared with 24% of patients in the voriconazole group. Favorable responses to OLAT in the amphotericin B deoxycholate group occurred in only 19% of patients with initial insufficient response and 38% of patients with intolerance. Salvage therapy with a lipid formulation of amphotericin B after initial treatment with amphotericin B deoxycholate was successful for only 30% of patients (14 of 47). Treatment success among patients randomized to receive amphotericin B, including those whose treatment was switched to OLAT, was 32%, compared with 55% among patients who received voriconazole alone (P<.001).
  
  
  CONCLUSIONS
  This study highlights the limited efficacy of salvage antifungal therapy, including therapy with lipid formulations of amphotericin B, and demonstrates the importance of effective initial therapy in invasive aspergillosis.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA. patterson@uthscsa.edu
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Patterson
authors.forename: Helen W
authors.initials: HW
authors.lastname: Boucher
authors.forename: Raoul
authors.initials: R
authors.lastname: Herbrecht
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Patricia
authors.initials: P
authors.lastname: Ribaud
authors.forename: Robert H
authors.initials: RH
authors.lastname: Rubin
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.forename: Ben
authors.initials: B
authors.lastname: DePauw
authors.forename: Haran T
authors.initials: HT
authors.lastname: Schlamm
authors.forename: Peter
authors.initials: P
authors.lastname: Troke
authors.forename: John E
authors.initials: JE
authors.lastname: Bennett
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D003840:Deoxycholic Acid / Q000627:therapeutic use*; D004338:Drug Combinations; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D016879:Salvage Therapy; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D011743:Pyrimidines; D014230:Triazoles; D003840:Deoxycholic Acid; D017964:Itraconazole; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; D065819:Voriconazole