Rebekah Lane

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.

Background: Understanding the epidemiology of invasive non-Aspergillus mold infections is essential to inform effective therapy. This study aimed to determine the epidemiology and infection characteristics of non-Aspergillus mold infections in Australasia. Methods: A 21-center, retrospective study of proven/probable non-Aspergillus mold infections from 2016 to 2023 was conducted in Australia and New Zealand. Data collected included demographic, clinical, microbiological, treatment, and outcome information through 180 days of follow-up. Results: Of 421 cases, 346 (82.2%) were proven infections and 315 (74.8%) were localized. Lung (n = 150, 35.6%) was the most common site of infection. Twenty cases (4.8%) were due to >1 non-Aspergillus mold pathogen, resulting in 443 isolates in total. Dematiaceous molds, inclusive of Lomentospora prolificans (n = 96 of 443, 21.7%), Scedosporium spp. (n = 87 of 443, 19.6%), and other dematiaceous molds of various genera (n = 48 of 443, 10.8%), were the most common (n = 231 of 443, 52.1%), followed by Mucorales (n = 141 of 443, 31.8%). Common underlying conditions were hematological malignancy (n = 146, 34.7%) and diabetes mellitus (n = 122, 29.0%), while 68 cases (16.2%) had no comorbidities. One-third (n = 138, 32.8%) of patients received antifungal prophylaxis 30 days before non-Aspergillus mold diagnosis, and L. prolificans was the most common cause of breakthrough infections (P < .001). All-cause 90-day mortality was 31.4% (n = 132 of 421), with higher mortality observed in L. prolificans (n = 51 of 89, 57.3%) and Mucorales (n = 56 of 129, 43.4%) infections. Conclusions: Lomentospora prolificans, Scedosporium spp., and Mucorales are the most frequent non-Aspergillus mold pathogens in Australasia, with other emerging species and mixed infections encountered. Mortality from L. prolificans and Mucorales infections remains high.

Background: Limited data exist regarding outcomes of cryptococcosis in patients without human immunodeficiency virus (HIV), and few studies have compared outcomes of Cryptococcus gattii versus Cryptococcus neoformans infection. Methods: We conducted a retrospective study in 46 Australian and New Zealand hospitals to determine the outcomes of cryptococcosis in patients without HIV diagnosed between 2015 and 2019 and compared outcomes of C. gattii versus C. neoformans infections. Multivariable analysis identified predictors of mortality within 1 year. Results: Of 426 patients, 1-year all-cause mortality was 21%. Cryptococcus gattii infection was associated with lower mortality than C. neoformans (adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], .23–.95), while severe neurological symptoms at presentation were the strongest predictor of death (adjusted OR, 8.46; 95% CI, 2.99–23.98). Almost all (99.5%) patients with central nervous system (CNS) infection received induction antifungal therapy versus 27.7% with isolated pulmonary cryptococcosis. The most common regimen in CNS disease was liposomal amphotericin B with flucytosine (93.8%; mean duration, 31 ± 13 days). Among patients with CNS cryptococcosis, C. gattii infection was associated with higher risk of immune reconstitution inflammatory response (C-IRIS) than C. neoformans (21% versus 3%, P < .001). Nineteen patients received amphotericin B-based re-induction therapy for suspected relapse, but none had microbiological relapse. Serum cryptococcal antigen positivity and lung imaging abnormalities resolved slowly (resolution at 1 year in 25% and 34% of patients, respectively). Conclusions: Compared with C. neoformans, C. gattii infection demonstrated lower mortality but higher C-IRIS risk in CNS infection. Severe neurological symptoms were the strongest predictor of mortality.

CMV-infected monocytes are unable to phagocytose fungal pathogens yet produce inflammation associated with rejection and GVHD.