title: Posaconazole as salvage therapy in patients with invasive fungal infections after solid organ transplant.
abstract: BACKGROUND
  The incidence of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients has increased during the past 20 years and is associated with significant morbidity and mortality. In this post hoc analysis of a large, open-label, multicenter study, we evaluated efficacy and safety of posaconazole, a new extended-spectrum triazole, as salvage therapy for IFIs in SOT recipients.
  
  
  METHODS
  Twenty-three SOT recipients with proven or probable IFI and evidence of disease refractory to, or intolerant of, standard antifungal therapies received posaconazole oral suspension (40 mg/mL) 800 mg daily in divided doses. An independent, blinded data-review committee assessed patient diagnosis and outcome.
  
  
  RESULTS
  Complete or partial response was documented in 13 of 23 (57%) SOT recipients with proven or probable IFIs, including 1 of 2 (50%) refractory patients, 5 of 8 (63%) intolerant to prior therapy, and 7 of 13 (54%) who were both. Successes by type of IFI included 7 of 12 with invasive aspergillosis, 2 of 2 with invasive fusariosis, 1 of 1 with cryptococcosis, and 1 of 2 with zygomycosis. Treatment-related adverse events (TRAEs) were reported in 12 of 23 patients. Severe TRAEs occurred in 4 of 23 patients including increased levels of cyclosporine or tacrolimus requiring immunosuppressive dose adjustments in three patients and in one, termination of posaconazole. Severe TRAEs associated with renal and liver toxicities were uncommon.
  
  
  CONCLUSIONS
  Posaconazole was well tolerated and effective against IFIs including invasive aspergillosis, zygomycosis, fusariosis, and cryptococcosis in SOT recipients intolerant of or failing other antifungal therapies. Calcineurin inhibitor levels should be closely monitored in patients treated concomitantly with posaconazole to avoid toxicity from drug interaction.
authors.affiliation: Division of Infectious Diseases and International Health, Box 3035, Duke University Medical Center, Durham, NC 27710, USA. alexa011@mc.duke.edu
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Alexander
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Daly
authors.forename: Angela
authors.initials: A
authors.lastname: Restrepo
authors.forename: Angela M
authors.initials: AM
authors.lastname: Tobón
authors.forename: Hernando
authors.initials: H
authors.lastname: Patino
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Hardalo
authors.forename: John R
authors.initials: JR
authors.lastname: Graybill
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy; D002177:Candidiasis / Q000188:drug therapy; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000453:epidemiology; D016377:Organ Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications / Q000188:drug therapy / Q000382:microbiology; D012189:Retrospective Studies; D012449:Safety; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D014230:Triazoles; C101425:posaconazole