Mucorales: A systematic review to inform the World Health Organization priority list of fungal pathogens

Author:

Morrissey C Orla1ORCID,Kim Hannah Yejin234ORCID,Garnham Katherine5ORCID,Dao Aiken267ORCID,Chakrabarti Arunaloke8ORCID,Perfect John R9ORCID,Alastruey-Izquierdo Ana10ORCID,Harrison Thomas S1112ORCID,Bongomin Felix13ORCID,Galas Marcelo14,Siswanto Siswanto15,Dagne Daniel Argaw16,Roitberg Felipe17,Gigante Valeria18ORCID,Sati Hatim18ORCID,Alffenaar Jan-Willem234ORCID,Beardsley Justin2419ORCID

Affiliation:

1. Department of Infectious Diseases, Alfred Health and Monash University , Melbourne, Victoria , Australia

2. Infectious Diseases Institute (Sydney ID), The University of Sydney , Camperdown, New South Wales , Australia

3. Faculty of Medicine and Health, School of Pharmacy, The University of Sydney , Camperdown, New South Wales , Australia

4. Department of Pharmacy, Westmead Hospital , Westmead, New South Wales , Australia

5. Department of Infectious Diseases and Microbiology, Gold Coast University Hospital , Southport, Queensland , Australia

6. Department of Infectious Diseases, Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Camperdown, New South Wales , Australia

7. Orthopaedic Research and Biotechnology Unit, Children’s Hospital at Westmead , Westmead, New South Wales , Australia

8. Doodhadhari Burfani Hospital and Research Institute , Haridwar , India

9. Division of Infectious Diseases and International Health, Duke University School of Medicine , Durham, North Carolina , USA

10. Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III , Majadahonda, Madrid , Spain

11. Institute for Infection and Immunity, and Clinical Academic Group in Infection and Immunity, St. George’s, University of London, and St. George's University Hospitals NHS Foundation Trust , London , United Kingdom

12. MRC Centre for Medical Mycology, University of Exeter , Exeter , United Kingdom

13. Department of Medical Microbiology and Immunology, Faculty of Medicine, Gulu University , Gulu , Uganda

14. Antimicrobial Resistance Special Program, Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization , Washington, District of Columbia , USA

15. World Health Organization, South-East Asia Region Office , New Delhi , India

16. Department of Control of Neglected Tropical Diseases, World Health Organization , Geneva , Switzerland

17. Department of Noncommunicable Diseases, World Health Organization , Geneva , Switzerland

18. AMR Division, World Health Organization , Geneva , Switzerland

19. Westmead Institute for Medical Research , Westmead, New South Wales , Australia

Abstract

Abstract The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%–85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%–100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094–0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.

Funder

Ministry of Education and Science

World Health Organization

Publisher

Oxford University Press (OUP)

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