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

Shio Yen Tio; Sharon C-A Chen; Kate Hamilton; Christopher H Heath; Alyssa Pradhan; Arthur J Morris; Tony M Korman; Orla Morrissey; Catriona L Halliday; Sarah Kidd; Timothy Spelman; Nadiya Brell; Brendan McMullan; Julia E Clark; Katerina Mitsakos; Robyn P Hardiman; Phoebe Williams; Anita J Campbell; Justin Beardsley; Sebastiaan Van Hal; Michelle K Yong; Leon J Worth; Monica A Slavin

doi:10.1016/j.lanwpc.2023.100888

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

Lancet Reg Health West Pac. 2023 Sep 4:40:100888. doi: 10.1016/j.lanwpc.2023.100888. eCollection 2023 Nov.

Authors

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.

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.