Invasive aspergillosis in adult patients in Australia and New Zealand: 2017-2020

doi:10.1016/j.lanwpc.2023.100888

. 2023 Sep 4:40:100888.

doi: 10.1016/j.lanwpc.2023.100888. eCollection 2023 Nov.

Invasive aspergillosis in adult patients in Australia and New Zealand: 2017-2020

Shio Yen Tio^{1

2

3

4}, Sharon C-A Chen^{5

6}, Kate Hamilton⁵, Christopher H Heath^{7

8

9}, Alyssa Pradhan^{10

6}, Arthur J Morris¹¹, Tony M Korman¹², Orla Morrissey¹³, Catriona L Halliday^{5

6}, Sarah Kidd¹⁴, Timothy Spelman^{15

16}, Nadiya Brell^{10

17}, Brendan McMullan^{18

19}, Julia E Clark^{20

21}, Katerina Mitsakos²², Robyn P Hardiman²², Phoebe Williams^{18

23}, Anita J Campbell^{24

25}, Justin Beardsley^{26

27

28}, Sebastiaan Van Hal^{6

29}, Michelle K Yong^{1

2

3

4}, Leon J Worth^{1

2

4}, Monica A Slavin^{1

2

3

4}

Affiliations

¹ Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia.
² National Centre for Infections in Cancer, Melbourne, Australia.
³ Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Australia.
⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia.
⁵ Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, Sydney, Australia.
⁶ School of Medicine, University of Sydney, Australia.
⁷ Department of Microbiology, PathWest Laboratory Medicine, Murdoch, Western Australia, Australia.
⁸ Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
⁹ Department of Medicine, University of Western Australia, Crawley, Western Australia, Australia.
¹⁰ Prince of Wales Hospital, Southeast Sydney LHD, NSW Health Pathology, Australia.
¹¹ Auckland City Hospital, 2 Park Road, Grafton, Auckland 1023, New Zealand.
¹² Monash University and Monash Health, Clayton, Victoria, Australia.
¹³ Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia.
¹⁴ National Mycology Reference Centre, Microbiology & Infectious Diseases, SA Pathology, Adelaide, South Australia, Australia.
¹⁵ Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
¹⁶ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁷ University of New South Wales, Australia.
¹⁸ Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Australia.
¹⁹ School of Clinical Medicine, Faculty of Medicine and Health, UNSW, Australia.
²⁰ Infection Management Service, Queensland Children's Hospital, Children's Health Queensland, Brisbane 4101, Australia.
²¹ School of Clinical Medicine, CHQCU, University of Queensland, Australia.
²² Department of Infectious Disease and Microbiology, Royal North Shore Hospital, Sydney, Australia.
²³ School of Public Health, Faculty of Medicine, The University of Sydney, Australia.
²⁴ Department of Infectious Diseases, Perth Children's Hospital, Western Australia, Australia.
²⁵ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Western Australia, Australia.
²⁶ University of Sydney Infectious Disease Institute, Australia.
²⁷ Westmead Hospital, Western Sydney LHD, NSW Health, Australia.
²⁸ Westmead Institute for Medical Research, Australia.
²⁹ Department of Infectious Diseases and Microbiology Royal Prince Alfred Hospital, Australia.

PMID: 37701716
PMCID: PMC10494171
DOI: 10.1016/j.lanwpc.2023.100888

Invasive aspergillosis in adult patients in Australia and New Zealand: 2017-2020

Shio Yen Tio et al. Lancet Reg Health West Pac. 2023.

. 2023 Sep 4:40:100888.

doi: 10.1016/j.lanwpc.2023.100888. eCollection 2023 Nov.

Authors

Affiliations

¹ Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia.
² National Centre for Infections in Cancer, Melbourne, Australia.
³ Department of Infectious Diseases, Royal Melbourne Hospital, Melbourne, Australia.
⁴ Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia.
⁵ Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, Sydney, Australia.
⁶ School of Medicine, University of Sydney, Australia.
⁷ Department of Microbiology, PathWest Laboratory Medicine, Murdoch, Western Australia, Australia.
⁸ Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
⁹ Department of Medicine, University of Western Australia, Crawley, Western Australia, Australia.
¹⁰ Prince of Wales Hospital, Southeast Sydney LHD, NSW Health Pathology, Australia.
¹¹ Auckland City Hospital, 2 Park Road, Grafton, Auckland 1023, New Zealand.
¹² Monash University and Monash Health, Clayton, Victoria, Australia.
¹³ Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia.
¹⁴ National Mycology Reference Centre, Microbiology & Infectious Diseases, SA Pathology, Adelaide, South Australia, Australia.
¹⁵ Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
¹⁶ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁷ University of New South Wales, Australia.
¹⁸ Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Australia.
¹⁹ School of Clinical Medicine, Faculty of Medicine and Health, UNSW, Australia.
²⁰ Infection Management Service, Queensland Children's Hospital, Children's Health Queensland, Brisbane 4101, Australia.
²¹ School of Clinical Medicine, CHQCU, University of Queensland, Australia.
²² Department of Infectious Disease and Microbiology, Royal North Shore Hospital, Sydney, Australia.
²³ School of Public Health, Faculty of Medicine, The University of Sydney, Australia.
²⁴ Department of Infectious Diseases, Perth Children's Hospital, Western Australia, Australia.
²⁵ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Western Australia, Australia.
²⁶ University of Sydney Infectious Disease Institute, Australia.
²⁷ Westmead Hospital, Western Sydney LHD, NSW Health, Australia.
²⁸ Westmead Institute for Medical Research, Australia.
²⁹ Department of Infectious Diseases and Microbiology Royal Prince Alfred Hospital, Australia.

PMID: 37701716
PMCID: PMC10494171
DOI: 10.1016/j.lanwpc.2023.100888

Abstract

Background: New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice.

Methods: The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017-December 2020). Descriptive analyses were used to report patients' demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM).

Findings: Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria - 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51-69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04-3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93-8.17, p < 0.001) but not neutropenia (HR 1.45; 95% CI 0.88-2.39, p = 0.135) were associated with mortality. Chronic kidney disease was also a significant predictor of death in the HM subgroup (HR 3.94; 95% CI 1.15-13.44, p = 0.028).

Interpretation: IA is identified in high number of patients with mild/no immunosuppression in our study. The relatively high proportion of non-A. fumigatus species complex isolates and 6.5% azole-resistance rate amongst A. fumigatus sensu stricto necessitates accurate species identification and susceptibility testing for optimal patient outcomes.

Funding: This work is unfunded. All authors' financial disclosures are listed in detail at the end of the manuscript.

Keywords: Australasia; Epidemiology; Invasive aspergillosis; Outcome.

PubMed Disclaimer

Conflict of interest statement

This work itself is not funded. All authors declare no conflicts of interest associated with this publication, or any financial support that could have influenced its outcome.

Figures

**Fig. 1**
Number of patients with causative *Aspergillus* species identified and methods of identification.

**Fig. 2**
Kaplan–Meier survival curve stratified by: a) presence or absence of haematologic malignancy for the entire cohort (total 220 patients, as one patient’s date of death was not captured); b) ICU admission for the entire cohort (total 220 patients, as one patient’s date of death was not captured); c) presence or absence of chronic kidney disease for the haematologic malignancy subgroup only (total 110 patients); d) ICU admission for the haematologic malignancy subgroup only (total 110 patients).

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[1] Ghez D., Calleja A., Protin C., et al. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib. Blood. 2018;131(17):1955–1959. - PubMed

[2] Ghez D., Calleja A., Protin C., et al. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib. Blood. 2018;131(17):1955–1959. - PubMed

[3] Park J.H., Romero F.A., Taur Y., et al. Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells. Clin Infect Dis. 2018;67(4):533–540. - PMC - PubMed

[4] Park J.H., Romero F.A., Taur Y., et al. Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells. Clin Infect Dis. 2018;67(4):533–540. - PMC - PubMed

[5] Bulpa P., Dive A., Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J. 2007;30(4):782–800. - PubMed

[6] Bulpa P., Dive A., Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J. 2007;30(4):782–800. - PubMed

[7] Blot S.I., Taccone F.S., Van den Abeele A.M., et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2012;186(1):56–64. - PubMed

[8] Blot S.I., Taccone F.S., Van den Abeele A.M., et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2012;186(1):56–64. - PubMed

[9] Verweij P.E., Rijnders B.J.A., Bruggemann R.J.M., et al. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion. Intensive Care Med. 2020;46(8):1524–1535. - PMC - PubMed

[10] Verweij P.E., Rijnders B.J.A., Bruggemann R.J.M., et al. Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion. Intensive Care Med. 2020;46(8):1524–1535. - PMC - PubMed

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Invasive aspergillosis in adult patients in Australia and New Zealand: 2017-2020

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Invasive aspergillosis in adult patients in Australia and New Zealand: 2017-2020

Authors

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Abstract

Conflict of interest statement

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