title: Treatment of invasive pulmonary aspergillosis in neutropenic patients by additional bronchoscopic amphotericin B instillation.
abstract: BACKGROUND
  Invasive pulmonary aspergillosis (IPA) remains a life-threatening condition despite systemic antifungal therapy.
  
  
  OBJECTIVE
  This retrospective analysis investigated whether additional bronchoscopic instillation of amphotericin B (amB) would improve efficacy of antifungal treatment in patients with haematological malignancies suffering from IPA.
  
  
  METHODS
  Twenty patients (40.6 +/- 14.2 years, 14 male) with preceding chemotherapy, bone marrow or stem cell transplantation complicated by severe IPA who did not respond sufficiently to systemic antifungal therapy were additionally treated by repeated bronchoscopic instillations of amB solution (91 instillations, on average 4.6 +/- 2.2 instillations per patient over a period of 24.1 +/- 21.0 days). Therapeutic response to this combined treatment regimen was monitored by chest X-ray and CT scan.
  
  
  RESULTS
  The mean infiltration sizes during systemic antifungal therapy alone (mean duration 11.9 +/- 9.9 days) did not change significantly. However, after additional bronchoscopic instillation of amB solution infiltration sizes were reduced significantly (p < 0.05). A total resolution of infiltrates was seen in 3 and a partial reduction in 13 of 20 patients. Mean duration of total antifungal treatment was 50.1 +/- 24.0 days. The mean follow-up period was 34.1 +/- 31.2 months. The IPA-related mortality rate was 18.8% (3 of 16 patients).
  
  
  CONCLUSIONS
  Additional bronchoscopic instillation of amB may improve the efficacy of systemic antifungal therapy in patients with haematological malignancies complicated by severe IPA. Bronchoscopic instillation of amB should be considered as an additional treatment option in cases with IPA unresponsive to systemic therapy.
authors.affiliation: Pulmonary Unit, Department of Internal Medicine, University of Leipzig, Leipzig, Germany. lungewinkler@aol.com
authors.forename: J
authors.initials: J
authors.lastname: Winkler
authors.forename: U
authors.initials: U
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Nenoff
authors.forename: H-J
authors.initials: HJ
authors.lastname: Seyfarth
authors.forename: M
authors.initials: M
authors.lastname: Vogtmann
authors.forename: G
authors.initials: G
authors.lastname: Borte
authors.forename: W
authors.initials: W
authors.lastname: Pönisch
authors.forename: T
authors.initials: T
authors.lastname: Kahn
authors.forename: H
authors.initials: H
authors.lastname: Wirtz
authors.forename: J
authors.initials: J
authors.lastname: Schauer
authors.forename: G
authors.initials: G
authors.lastname: Hoheisel
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage*; D000935:Antifungal Agents / Q000008:administration & dosage*; D001228:Aspergillosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D001999:Bronchoscopy; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D008172:Lung Diseases, Fungal / Q000150:complications* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications*; D011859:Radiography; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B