Management, Outcomes, and Factors Associated with Mortality and Treatment Failure of Non- Aspergillus Mold Infections: A Multicenter Study in Australia and New Zealand
Chin Fen Neoh, Sharon C-A Chen, Arthur J Morris, Christopher H Heath, Shu Jin Tan, Rebekah Lane, Shio Yen Tio, Sze Yen Tay, Matthew B Roberts, Karina Kennedy, Sebastiaan J van Hal, Hugh C Murray, Robert Pickles, Natasha Marcella Vaselli, Abby Douglas, Karen Urbancic, Mahesh Menon, Adam Stewart, Julia C Howard, Caitlin Keighley, Spiros Miyakis, Rohan Beresford, Louise Cooley, Marjoree Sehu, Catriona L Halliday, Sarah Kidd, David C M Kong, Tim Spelman, Leon J Worth, Monica A Slavin, , Amy Crowe, Jane Davies, Michelle England, Dianne Gardam, Rupert Handy, May E Leitch, Catherine Marshall, Sarah Lynar, Owen Robinson, Philip Selby, Olivia Smibert, Peter Simos, Michelle K Yong, Kar Yee YongAbstract
Background
Very few large regional studies have evaluated treatment responses and mortality across different non-Aspergillus mold infections.
Methods
We conducted a retrospective, 21-center, observational study of non-Aspergillus mold infections in Australia and New Zealand. Cases from 2016 to 2023 were identified from each hospital’s pathology system. Treatment modalities were evaluated, and outcomes (e.g. treatment response, mortality) were compared across non-Aspergillus mold infections at day 30, 90 and 180 follow-up. Multivariable analyses were performed to identify factors associated with 90-day mortality and treatment failure.
Results
Of 421 cases, 129 were Mucorales (30.6%), 89 Lomentospora prolificans (21.1%), 82 Scedosporium spp. (19.5%), 30 Fusarium spp. (7.1%), 44 other dematiaceous molds (10.5%), 27 other non-Aspergillus molds (6.4%), and 20 mixed non-Aspergillus mold infections (4.8%). Antifungal therapy was administered in 376 (89.3%), and 219 (52.0%) underwent adjunctive surgery. Among those who survived by day 180, 42.6% (n=115/270) remained on antifungals, with total duration exceeding 180 days. All-cause 90-day mortality was 31.4% (n=132/421), being the highest in Lomentospora prolificans infection (n=51/89, 57.3%). Neutropenia [hazard ratio (HR):2.19, 95% confidence interval (CI):1.30-3.69], intensive care unit admission (HR:2.51, 95%CI:1.60-3.92), disseminated infection (HR:2.55, 95%CI:1.59-4.10), Mucorales (HR:4.87, 95%CI:2.71-8.77) and L. prolificans infections (HR:3.71, 95%CI:1.97-6.98) were associated with increased 90-day mortality (all p<0.001). Adjunctive surgery was associated with a lower 90-day mortality (HR:0.34, 95%CI:0.21-0.54, p<0.001). Factors associated with 90-day treatment failure included neutropenia, prolonged corticosteroid use, solid cancer, disseminated infection, central nervous system infection, and L. prolificans infections (all p<0.05).
Conclusions
Despite antifungal therapy, L. prolificans infections had the poorest clinical outcomes followed by Mucorales, highlighting the need for improved diagnostic methods and therapeutic strategies.