Antifungal therapy and management of Complications of cryptococcosis due to Cryptococcus gattii

Sharon Chen, Tony Korman, Monica Slavin, Debbie Marriott, Karen Byth, N Bak, Bart Currie, Krispin Hajkowicz, Christopher Heath, Sarah Kidd, William McBride, Wieland Meyer, Ronan Murray, Geoffrey Playford, Tania C Sorrell

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Background: We describe antifungal therapy andmanagement of complications due to Cryptococcus gattii infection in 86 Australian patients followed for at least12 months.


Methods: Patient data from culture-confirmedcases (2000–2007) were recorded at diagnosis, 6 weeks, 6 months, and 12 months.Clinical, laboratory, and treatment variables associated with raisedintracranial pressure (ICP) and immune reconstitution inflammatory syndrome(IRIS) were determined.


Results: Seven of 10 patients with lung infectionreceived amphotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC]for a median of 2 weeks); median duration of therapy including azole eradicationtherapy was 41 weeks, with a complete/partial clinical response in 78%. Forneurologic disease, 88% of patients received AMB, 78% with 5-FC, for a medianof 6 weeks. The median total course was 18 months. Nine patients receivingfluconazole induction therapy were reinduced with AMB plus 5-FC for clinicalfailure. Raised ICP (31 patients) was associated with initial abnormalneurology, and neurologic sequelae and/or death at 12 months (both P = .02); cerebrospinal fluiddrains/shunts were placed in 58% of patients and in 64% of 22 patients withhydrocephalus. IRIS developed 2–12 months after starting antifungals in 8patients, who presented with new/enlarging brain lesions. Risk factors includedfemale sex, brain involvement at presentation, and higher median CD4 counts(all P < .05); corticosteroids reducedcryptococcoma-associated edema.


Conclusions: Induction AMB plus 5-FC is indicated for C. gattii neurologic cryptococcosis (6weeks) and when localized to lung (2 weeks). Shunting was often required tocontrol raised ICP. IRIS presents with cerebral manifestations.

Original languageEnglish
Pages (from-to)543-551
Number of pages9
JournalClinical Infectious Diseases
Issue number4
Publication statusPublished - 15 Aug 2013


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