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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    Abstract

    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
    Volume57
    Issue number4
    DOIs
    Publication statusPublished - 15 Aug 2013

    Fingerprint

    Cryptococcus gattii
    Cryptococcosis
    Flucytosine
    Immune Reconstitution Inflammatory Syndrome
    Amphotericin B
    Therapeutics
    Azoles
    Lung
    Brain
    CD4 Lymphocyte Count
    Nervous System
    Edema
    Adrenal Cortex Hormones
    Pressure

    Cite this

    Chen, S., Korman, T., Slavin, M., Marriott, D., Byth, K., Bak, N., ... Sorrell, T. C. (2013). Antifungal therapy and management of Complications of cryptococcosis due to Cryptococcus gattii. Clinical Infectious Diseases, 57(4), 543-551. https://doi.org/10.1093/cid/cit341
    Chen, Sharon ; Korman, Tony ; Slavin, Monica ; Marriott, Debbie ; Byth, Karen ; Bak, N ; Currie, Bart ; Hajkowicz, Krispin ; Heath, Christopher ; Kidd, Sarah ; McBride, William ; Meyer, Wieland ; Murray, Ronan ; Playford, Geoffrey ; Sorrell, Tania C. / Antifungal therapy and management of Complications of cryptococcosis due to Cryptococcus gattii. In: Clinical Infectious Diseases. 2013 ; Vol. 57, No. 4. pp. 543-551.
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    title = "Antifungal therapy and management of Complications of cryptococcosis due to Cryptococcus gattii",
    abstract = "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.",
    author = "Sharon Chen and Tony Korman and Monica Slavin and Debbie Marriott and Karen Byth and N Bak and Bart Currie and Krispin Hajkowicz and Christopher Heath and Sarah Kidd and William McBride and Wieland Meyer and Ronan Murray and Geoffrey Playford and Sorrell, {Tania C}",
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    Chen, S, Korman, T, Slavin, M, Marriott, D, Byth, K, Bak, N, Currie, B, Hajkowicz, K, Heath, C, Kidd, S, McBride, W, Meyer, W, Murray, R, Playford, G & Sorrell, TC 2013, 'Antifungal therapy and management of Complications of cryptococcosis due to Cryptococcus gattii', Clinical Infectious Diseases, vol. 57, no. 4, pp. 543-551. https://doi.org/10.1093/cid/cit341

    Antifungal therapy and management of Complications of cryptococcosis due to Cryptococcus gattii. / Chen, Sharon; Korman, Tony; Slavin, Monica; Marriott, Debbie; Byth, Karen; Bak, N; Currie, Bart; Hajkowicz, Krispin; Heath, Christopher; Kidd, Sarah; McBride, William; Meyer, Wieland; Murray, Ronan; Playford, Geoffrey; Sorrell, Tania C.

    In: Clinical Infectious Diseases, Vol. 57, No. 4, 15.08.2013, p. 543-551.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Antifungal therapy and management of Complications of cryptococcosis due to Cryptococcus gattii

    AU - Chen, Sharon

    AU - Korman, Tony

    AU - Slavin, Monica

    AU - Marriott, Debbie

    AU - Byth, Karen

    AU - Bak, N

    AU - Currie, Bart

    AU - Hajkowicz, Krispin

    AU - Heath, Christopher

    AU - Kidd, Sarah

    AU - McBride, William

    AU - Meyer, Wieland

    AU - Murray, Ronan

    AU - Playford, Geoffrey

    AU - Sorrell, Tania C

    PY - 2013/8/15

    Y1 - 2013/8/15

    N2 - 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.

    AB - 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.

    U2 - 10.1093/cid/cit341

    DO - 10.1093/cid/cit341

    M3 - Article

    VL - 57

    SP - 543

    EP - 551

    JO - Clinical Infectious Diseases

    JF - Clinical Infectious Diseases

    SN - 1058-4838

    IS - 4

    ER -