Management, Outcomes, and Factors Associated With Mortality and Treatment Failure of Non-Aspergillus Mold Infections: A Multicenter Study in Australia and New Zealand

BACKGROUND: Few large studies have evaluated treatment responses and mortality across 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. Treatments were recorded and outcomes 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 survivors at 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), highest in L. 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 < .001). Adjunctive surgery was associated with a lower 90-day mortality (HR: 0.34, 95% CI: .21-.54, P < .001). 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.