Multicenter Study

. 2025 Apr 30;80(4):817-825.

doi: 10.1093/cid/ciae630.

Management, Outcomes, and Predictors of Mortality of Cryptococcus Infection in Patients Without HIV: A Multicenter Study in 46 Hospitals in Australia and New Zealand

Julien Coussement^{1

2}, Christopher H Heath^{3

4}, Matthew B Roberts^{5

6}, Rebekah J Lane⁷, Tim Spelman^{8

9

10

11}, Olivia C Smibert¹², Anthony Longhitano¹³, C Orla Morrissey^{14

15}, Blake Nield¹⁶, Monica Tripathy¹⁷, Joshua S Davis¹⁸, Karina J Kennedy¹⁹, Sarah A Lynar^{20

21}, Lucy C Crawford²⁰, Simeon J Crawford²², Benjamin J Smith²³, Andrew P Gador-Whyte²⁴, Rose Haywood²⁵, Andrew A Mahony²⁶, Julia C Howard²⁷, Genevieve B Walls²⁸, Gabrielle M O'Kane^{29

30}, Matthew T Broom^{31

32}, Caitlin L Keighley³³, Olivia Bupha-Intr³⁴, Louise Cooley³⁵, Jennifer A O'Hern^{20

36}, Justin D Jackson³⁷, Arthur J Morris⁷, Caroline Bartolo³⁸, Adrian R Tramontana^{39

40}, Katherine C Grimwade^{41

42}, Victor Au Yeung⁴³, Roy Chean⁴⁴, Emily Woolnough⁴⁵, Benjamin W Teh¹, Monica A Slavin^{1

46}, Sharon C A Chen⁴⁷; Australian and New Zealand Study Group for Cryptococcosis in Patients Without HIV Infection

Collaborators, Affiliations

Collaborators

Australian and New Zealand Study Group for Cryptococcosis in Patients Without HIV Infection:
Kylie Alcorn, Justin Beardsley, Aaron Bloch, Amy Crowe, Wendy Doyle, Michelle England, David Griffin, Kate Hamilton, Tony M Korman, Victoria Madigan, Hugh McGann, William Pratt, Sarah Sparham, Sebastiaan Van Hal, Prue Waters, Eloise Williams

Affiliations

¹ Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
² Department of Infectious Diseases, Guadeloupe University Hospital, Pointe-a-Pitre, Guadeloupe.
³ Department of Microbiology, PathWest Laboratory Medicine, and Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Washington, Australia.
⁴ Department of Infectious Diseases, Royal Perth Hospital, Perth, Washington, Australia.
⁵ Royal Adelaide Hospital, Adelaide, South Australia, Australia.
⁶ Flinders Medical Centre, Bedford Park, South Australia, Australia.
⁷ Auckland City Hospital, Te Toka Tumai, New Zealand.
⁸ Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
⁹ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁰ Burnet Institute, Melbourne, Victoria, Australia.
¹¹ University of Melbourne Department of Surgery, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
¹² Austin Health, Heidelberg, Victoria, Australia.
¹³ Monash Health, Clayton, Victoria, Australia.
¹⁴ Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia.
¹⁵ Department of Infectious Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁶ Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
¹⁷ Gold Coast Hospital and Health Service, Southport, Queensland, Australia.
¹⁸ John Hunter Hospital, Newcastle, New South Wales, Australia.
¹⁹ ACT Pathology, Canberra Health Services, Canberra, Australian Capital Territory, Australia.
²⁰ Royal Darwin and Palmerston Hospitals, Darwin, Northern Territory, Australia.
²¹ Menzies School of Health Research, Darwin, Northern Territory, Australia.
²² Wollongong Hospital, Wollongong, New South Wales, Australia.
²³ Eastern Health, Box Hill, Victoria, Australia.
²⁴ St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
²⁵ Prince of Wales Hospital, Sydney, New South Wales, Australia.
²⁶ Bendigo Health, Bendigo, Victoria, Australia.
²⁷ Te Whatu Ora Waikato, Hamilton, New Zealand.
²⁸ Middlemore Hospital, Te Whatu Ora Counties Manukau, Auckland, New Zealand.
²⁹ Gosford Hospital, Gosford, New South Wales, Australia.
³⁰ Wyong Hospital, Hamlyn Terrace, New South Wales, Australia.
³¹ North Shore Hospital, Te Whatu Ora Waitemata, Auckland, New Zealand.
³² Waitakere Hospital, Te Whatu Ora Waitemata, Auckland, New Zealand.
³³ Southern IML Pathology, Wollongong, New South Wales, Australia.
³⁴ Capital, Coast and Hutt Valley District, Wellington, New Zealand.
³⁵ Royal Hobart Hospital, Hobart, TAS, Australia.
³⁶ Launceston General Hospital, Launceston, TAS, Australia.
³⁷ Albury Wodonga Health, Albury, Victoria, Australia.
³⁸ Barwon Health, Geelong, Victoria, Australia.
³⁹ Western Health, Footscray, Victoria, Australia.
⁴⁰ Western Clinical School, Melbourne Medical School, the University of Melbourne, St Albans, Victoria, Australia.
⁴¹ Tauranga Hospital, Hauora a Toi Bay of Plenty, Tauranga, New Zealand.
⁴² Whakatane Hospital, Hauora a Toi Bay of Plenty, Whakatane, New Zealand.
⁴³ Ballarat Health Services, Ballarat, Victoria, Australia.
⁴⁴ Latrobe Regional Hospital, Traralgon, Victoria, Australia.
⁴⁵ St John of God Midland Public and Private Hospital, Midland, Washington, Australia.
⁴⁶ Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁴⁷ Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.

PMID: 39692570
DOI: 10.1093/cid/ciae630

Multicenter Study

Management, Outcomes, and Predictors of Mortality of Cryptococcus Infection in Patients Without HIV: A Multicenter Study in 46 Hospitals in Australia and New Zealand

Julien Coussement et al. Clin Infect Dis. 2025.

. 2025 Apr 30;80(4):817-825.

doi: 10.1093/cid/ciae630.

Authors

Collaborators

Australian and New Zealand Study Group for Cryptococcosis in Patients Without HIV Infection:
Kylie Alcorn, Justin Beardsley, Aaron Bloch, Amy Crowe, Wendy Doyle, Michelle England, David Griffin, Kate Hamilton, Tony M Korman, Victoria Madigan, Hugh McGann, William Pratt, Sarah Sparham, Sebastiaan Van Hal, Prue Waters, Eloise Williams

Affiliations

¹ Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
² Department of Infectious Diseases, Guadeloupe University Hospital, Pointe-a-Pitre, Guadeloupe.
³ Department of Microbiology, PathWest Laboratory Medicine, and Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Washington, Australia.
⁴ Department of Infectious Diseases, Royal Perth Hospital, Perth, Washington, Australia.
⁵ Royal Adelaide Hospital, Adelaide, South Australia, Australia.
⁶ Flinders Medical Centre, Bedford Park, South Australia, Australia.
⁷ Auckland City Hospital, Te Toka Tumai, New Zealand.
⁸ Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
⁹ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁰ Burnet Institute, Melbourne, Victoria, Australia.
¹¹ University of Melbourne Department of Surgery, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia.
¹² Austin Health, Heidelberg, Victoria, Australia.
¹³ Monash Health, Clayton, Victoria, Australia.
¹⁴ Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia.
¹⁵ Department of Infectious Diseases, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁶ Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
¹⁷ Gold Coast Hospital and Health Service, Southport, Queensland, Australia.
¹⁸ John Hunter Hospital, Newcastle, New South Wales, Australia.
¹⁹ ACT Pathology, Canberra Health Services, Canberra, Australian Capital Territory, Australia.
²⁰ Royal Darwin and Palmerston Hospitals, Darwin, Northern Territory, Australia.
²¹ Menzies School of Health Research, Darwin, Northern Territory, Australia.
²² Wollongong Hospital, Wollongong, New South Wales, Australia.
²³ Eastern Health, Box Hill, Victoria, Australia.
²⁴ St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia.
²⁵ Prince of Wales Hospital, Sydney, New South Wales, Australia.
²⁶ Bendigo Health, Bendigo, Victoria, Australia.
²⁷ Te Whatu Ora Waikato, Hamilton, New Zealand.
²⁸ Middlemore Hospital, Te Whatu Ora Counties Manukau, Auckland, New Zealand.
²⁹ Gosford Hospital, Gosford, New South Wales, Australia.
³⁰ Wyong Hospital, Hamlyn Terrace, New South Wales, Australia.
³¹ North Shore Hospital, Te Whatu Ora Waitemata, Auckland, New Zealand.
³² Waitakere Hospital, Te Whatu Ora Waitemata, Auckland, New Zealand.
³³ Southern IML Pathology, Wollongong, New South Wales, Australia.
³⁴ Capital, Coast and Hutt Valley District, Wellington, New Zealand.
³⁵ Royal Hobart Hospital, Hobart, TAS, Australia.
³⁶ Launceston General Hospital, Launceston, TAS, Australia.
³⁷ Albury Wodonga Health, Albury, Victoria, Australia.
³⁸ Barwon Health, Geelong, Victoria, Australia.
³⁹ Western Health, Footscray, Victoria, Australia.
⁴⁰ Western Clinical School, Melbourne Medical School, the University of Melbourne, St Albans, Victoria, Australia.
⁴¹ Tauranga Hospital, Hauora a Toi Bay of Plenty, Tauranga, New Zealand.
⁴² Whakatane Hospital, Hauora a Toi Bay of Plenty, Whakatane, New Zealand.
⁴³ Ballarat Health Services, Ballarat, Victoria, Australia.
⁴⁴ Latrobe Regional Hospital, Traralgon, Victoria, Australia.
⁴⁵ St John of God Midland Public and Private Hospital, Midland, Washington, Australia.
⁴⁶ Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁴⁷ Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.

PMID: 39692570
DOI: 10.1093/cid/ciae630

Abstract

Background: Limited data exist regarding outcomes of cryptococcosis in patients without human immunodeficiency virus (HIV), and few studies have compared outcomes of Cryptococcus gattii versus Cryptococcus neoformans infection.

Methods: We conducted a retrospective study in 46 Australian and New Zealand hospitals to determine the outcomes of cryptococcosis in patients without HIV diagnosed between 2015 and 2019 and compared outcomes of C. gattii versus C. neoformans infections. Multivariable analysis identified predictors of mortality within 1 year.

Results: Of 426 patients, 1-year all-cause mortality was 21%. Cryptococcus gattii infection was associated with lower mortality than C. neoformans (adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], .23-.95), while severe neurological symptoms at presentation were the strongest predictor of death (adjusted OR, 8.46; 95% CI, 2.99-23.98). Almost all (99.5%) patients with central nervous system (CNS) infection received induction antifungal therapy versus 27.7% with isolated pulmonary cryptococcosis. The most common regimen in CNS disease was liposomal amphotericin B with flucytosine (93.8%; mean duration, 31 ± 13 days). Among patients with CNS cryptococcosis, C. gattii infection was associated with higher risk of immune reconstitution inflammatory response (C-IRIS) than C. neoformans (21% versus 3%, P < .001). Nineteen patients received amphotericin B-based re-induction therapy for suspected relapse, but none had microbiological relapse. Serum cryptococcal antigen positivity and lung imaging abnormalities resolved slowly (resolution at 1 year in 25% and 34% of patients, respectively).

Conclusions: Compared with C. neoformans, C. gattii infection demonstrated lower mortality but higher C-IRIS risk in CNS infection. Severe neurological symptoms were the strongest predictor of mortality.

Keywords: Cryptococcus gattii; Cryptococcus neoformans; antifungal therapy; cryptococcosis; prognosis.

© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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Conflict of interest statement

Potential conflicts of interest . T. S. has received consulting fees from Biogen. O. M. has received grants from Gilead Sciences and Merck, Sharp and Dohme (MSD) Australia; honoraria from Gilead Sciences; and support for attending meetings from F2G and has participated on data and safety monitoring boards (DSMBs) or advisory boards for Gilead Sciences and MSD Australia. K. J. K. has received payment for expert testimony at the 46th Society of Hospital Pharmacists of Australia National Conference. A. R. T. has received honoraria from the Medical Journal of Australia. B. W. T. is supported by a Medical Research Future Fund Investigator Fellowship; has received grants from MSD and Seqirus and honoraria from Pfizer, Alexion, and Janssen; and has participated on DSMBs or advisory boards for CSLBehring, Takeda, and Moderna. S. C.-A. C. has received educational grants from F2G and MSD Australia. M. A. S. has received grants from Gilead Sciences, Merck, and F2G and honoraria from F2G and has participated on DSMBs or advisory boards for Pfizer, Cidara, and Roche. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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Management, Outcomes, and Predictors of Mortality of Cryptococcus Infection in Patients Without HIV: A Multicenter Study in 46 Hospitals in Australia and New Zealand

Collaborators

Affiliations

Management, Outcomes, and Predictors of Mortality of Cryptococcus Infection in Patients Without HIV: A Multicenter Study in 46 Hospitals in Australia and New Zealand

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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