Identifying Gaps in the International Consensus Case Definitions for Invasive Aspergillosis: A Review of Clinical Cases Not Meeting These Definitions

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

doi:10.1093/ofid/ofae594

Identifying Gaps in the International Consensus Case Definitions for Invasive Aspergillosis: A Review of Clinical Cases Not Meeting These Definitions

Open Forum Infect Dis. 2024 Oct 9;11(11):ofae594. doi: 10.1093/ofid/ofae594. eCollection 2024 Nov.

Authors

Shio Yen Tio^{1

2

3

4}, Sharon C A Chen^{5

6}, Christopher H Heath^{7

8

9}, Alyssa Pradhan^{6

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

6}, Sarah Kidd^{14

15}, Timothy Spelman^{16

17}, Nadiya Brell¹⁸, Brendan McMullan^{19

20}, Julia E Clark^{21

22}, Katerina Mitsakos²³, Robyn P Hardiman²³, Phoebe C M Williams^{19

24

25}, Anita J Campbell^{26

27}, Justin Beardsley^{25

28

29}, Sebastiaan Van Hal^{6

10}, 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, 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, New South Wales, Australia.
⁷ Department of Microbiology, PathWest Laboratory Medicine, Murdoch, Australia.
⁸ Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Australia.
⁹ Department of Medicine, University of Western Australia, Crawley, Australia.
¹⁰ Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, New South Wales, Australia.
¹¹ Auckland City Hospital, Auckland, New Zealand.
¹² Monash University and Monash Health, Clayton, Australia.
¹³ Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Australia.
¹⁴ National Mycology Reference Centre, Microbiology and Infectious Diseases, South Australia Pathology, Adelaide, Australia.
¹⁵ School of Biological Sciences, Faculty of Science Engineering & Technology, University of Adelaide, Adelaide, Australia.
¹⁶ Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
¹⁷ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
¹⁸ The Wollongong Hospital, New South Wales, Australia.
¹⁹ Department of Infectious Diseases, Sydney Children's Hospital, Randwick, Australia.
²⁰ School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales (UNSW), New South Wales, Australia.
²¹ Infection Management Service, Queensland Children's Hospital, Children's Health Queensland, Brisbane, Australia.
²² School of Clinical Medicine, Childrens Health Queensland Clinical Unit, University of Queensland, Queensland, Australia.
²³ Department of Infectious Disease and Microbiology, Royal North Shore Hospital, Sydney, Australia.
²⁴ School of Public Health, Faculty of Medicine, The University of Sydney, New South Wales, Australia.
²⁵ University of Sydney Infectious Diseases Institute, New South Wales, Australia.
²⁶ Department of Infectious Diseases, Perth Children's Hospital, Western Australia, Australia.
²⁷ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Western Australia, Australia.
²⁸ Westmead Hospital, Western Sydney Local Health District, NSW Health, New South Wales, Australia.
²⁹ Westmead Institute for Medical Research, New South Wales, Australia.

Abstract

Background: International consensus definitions for invasive aspergillosis (IA) in research are rigorous, yet clinically significant cases are often excluded from clinical studies for not meeting proven/probable IA case definitions. To better understand reasons for the failure to meet criteria for proven/probable infection, we herein review 47 such cases for their clinical and microbiological characteristics and outcomes.

Methods: Data on 47 cases that did not meet consensus IA definitions but were deemed significant were derived from a retrospective, observational, multicenter survey of 382 presumed IA cases across Australasia, of which findings of 221 proven/probable infections were recently published. The clinical, microbiological, and radiologic characteristics of these cases were analyzed. Mortality outcomes were compared with those of 221 proven/probable cases.

Results: Of 47 cases studied, 15 lacked classical host factors; 22 exhibited only a single positive Aspergillus polymerase chain reaction result; 7 lacked typical IA radiologic findings on chest computed tomography; and 3 had borderline galactomannan optical density indices (<1.0 but ≥0.5) in bronchoalveolar lavage fluid. The median age of patients was 61 years (IQR, 52-68); 34 were male (72%). Seven patients (15%) required intensive care admission. All patients had lung as the primary site of infection. Antifungal treatment was initiated in 42 patients (89%). All-cause 90-day mortality was 33%, similar to the 30% mortality in the comparative cohort (n = 221).

Conclusions: Our findings highlight the limitations of current consensus definitions for IA. Notably, the mortality of patients not meeting these definitions was similar to that of patients with proven/probable IA. Further studies, especially of patients with a single positive Aspergillus polymerase chain reaction result and those without host factors, are needed to determine if future consensus definitions may benefit from modifications.

Keywords: host factors; invasive aspergillosis; mortality; not meeting EORTC-MSGERC; single positive Aspergillus PCR.