title: Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii.
abstract: BACKGROUND
  We describe antifungal therapy and management of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least 12 months.
  
  
  METHODS
  Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months. Clinical, laboratory, and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution inflammatory syndrome (IRIS) were determined.
  
  
  RESULTS
  Seven of 10 patients with lung infection received amphotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC] for a median of 2 weeks); median duration of therapy including azole eradication therapy was 41 weeks, with a complete/partial clinical response in 78%. For neurologic disease, 88% of patients received AMB, 78% with 5-FC, for a median of 6 weeks. The median total course was 18 months. Nine patients receiving fluconazole induction therapy were reinduced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurologic sequelae and/or death at 12 months (both P = .02); cerebrospinal fluid drains/shunts were placed in 58% of patients and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation, and higher median CD4 counts (all P < .05); corticosteroids reduced cryptococcoma-associated edema.
  
  
  CONCLUSIONS
  Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.
authors.affiliation: Centre for Infectious Diseases and Microbiology and The Sydney Institute for Emerging Infections and Biosecurity, Sydney Medical School, University of Sydney, Australia. sharon.chen@swahs.health.nsw.gov.au
authors.forename: Sharon C-A
authors.initials: SC
authors.lastname: Chen
authors.forename: Tony M
authors.initials: TM
authors.lastname: Korman
authors.forename: Monica A
authors.initials: MA
authors.lastname: Slavin
authors.forename: Deborah
authors.initials: D
authors.lastname: Marriott
authors.forename: Karen
authors.initials: K
authors.lastname: Byth
authors.forename: Narin
authors.initials: N
authors.lastname: Bak
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Currie
authors.forename: Krispin
authors.initials: K
authors.lastname: Hajkowicz
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Heath
authors.forename: Sarah
authors.initials: S
authors.lastname: Kidd
authors.forename: William J H
authors.initials: WJ
authors.lastname: McBride
authors.forename: Wieland
authors.initials: W
authors.lastname: Meyer
authors.forename: Ronan
authors.initials: R
authors.lastname: Murray
authors.forename: E Geoffrey
authors.initials: EG
authors.lastname: Playford
authors.forename: Tania C
authors.initials: TC
authors.lastname: Sorrell
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use*; D001315:Australia; D003453:Cryptococcosis / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D056285:Cryptococcus gattii / Q000187:drug effects / Q000302:isolation & purification*; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use; D005437:Flucytosine / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine
keywords: Cryptococcus gattii; IRIS; antifungal therapy; neurologic complications