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 Lomentospora prolificans is an uncommon fungal pathogen known for its intrinsic resistance to conventional antifungal treatments. We present a challenging case of L. prolificans osteomyelitis and septic arthritis in an immunocompromised patient, highlighting the complexities of diagnosis and management. Case Presentation A rural, 65-year-old male smoker with rheumatoid arthritis, managed with immunosuppressants upadacitinib and prednisolone, presented with post-traumatic right elbow pain and swelling. He was initially treated for MSSA infection however, repeat cultures grew L. prolificans. Eight surgical washouts and debridements were undertaken. Antifungal treatment included voriconazole and terbinafine, and novel antifungal olorofim. Despite this, the patient experienced ongoing pain, purulent discharge, constitutional symptoms, and a non-functional elbow requiring trans-humeral amputation. Results At 12-month follow-up, the patient showed no signs of recurrent infection. Olorofim treatment was ceased, and prosthetic fitting was initiated. Immunosuppression for rheumatoid arthritis was reinitiated. Ongoing pain management and rehabilitation continue. Discussion L. prolificans osteoarticular infections are challenging, particularly in immunocompromised patients. Whilst novel antifungals including Olorofim show promise to improve outcomes, early surgical intervention is warranted.Successful management of L. prolificans osteomyelitis requires early recognition, aggressive surgical intervention, and novel antifungal therapies. This case emphasizes the importance of a multidisciplinary approach, the potential role of new antifungal agents, and the importance of function and quality of life in managing these uncommon albeit emerging and challenging infections.

ABSTRACT Sporotrichosis is a globally distributed subcutaneous mycosis caused mainly by Sporothrix brasiliensis , S. schenckii , and S. globosa . Cat-transmitted sporotrichosis, primarily caused by S. brasiliensis in South America and to a lesser extent by S. schenckii in Southeast Asia, is emerging as a substantial public health concern due to its outbreak potential. Itraconazole is the first-line drug for the treatment of humans and cats, but reduced susceptibility has been reported based on previously proposed epidemiological cut-off values (ECVs). To support resistance surveillance, we aimed to establish the Clinical and Laboratory Standards Institute (CLSI)-endorsed ECVs for these clinically relevant Sporothrix species. A total of 3,504 minimum inhibitory concentration (MIC) values for six antifungal agents (amphotericin B, itraconazole, posaconazole, voriconazole, isavuconazole, and terbinafine) were obtained from 19 international laboratories. Four of seven antifungals met the CLSI M57 guidelines criteria to determine the ECV. Established ECVs for amphotericin B were found to be high, with 8 µg/mL for S. brasiliensis and S. globosa , and 4 µg/mL for S. schenckii . Itraconazole ECVs were 4 µg/mL for S. brasiliensis and S. schenckii . Posaconazole ECVs were 4 µg/mL for all three species (tentative for S. globosa ), while the terbinafine ECV for S. brasiliensis was 0.12 µg/mL. Overall, this study establishes validated ECVs for key antifungals against Sporothrix species and identifies a low prevalence of non-wild-type (NWT) isolates (<10% except for S. schenckii and posaconazole), supporting ongoing antifungal resistance monitoring.

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.

Sporothrix species (Ascomycota, Ophiostomatales) are dimorphic fungi with diverse ecological niches, ranging from mammalian, plant, and insect pathogens to fungicolous organisms. Here, we describe Sporothrix davidellisii (CBS 147636T), a novel pathogenic species within the S. pallida complex isolated from a case of feline sporotrichosis in Melbourne, Australia. Phylogenetic analyses based on ITS, β-tubulin (BT2), calmodulin (CAL), and translation elongation factor 1-α (EF1-α) sequences confirmed its distinctiveness, with ITS sequence identity to its closest relative (S. chilensis) not exceeding 97.6%. The assembled genome is 39.02 Mb (eight contigs) with a 27.2 kb mitochondrial genome and a total of 12,631 predicted genes. Genetic diversity analyses revealed moderate nucleotide variation in the ITS region (π = 0.055), greater diversity in BT2 (π = 0.098), and CAL (π = 0.118), supporting its status as a unique species. Morphological studies revealed distinctive characteristics differentiating S. davidellisii from its nearest relatives, including elongated clavate sympodial conidia and sessile conidia. Notably, S. davidellisii exhibits yeast-like growth at 37°C, forming ellipsoid to ovoid budding cells in liquid media, although cigar-shaped yeasts, characteristic of highly virulent Sporothrix species, are rarely observed. This ability to transition to a yeast-like form, combined with its high-temperature tolerance (growth up to 40°C), underscores its opportunistic pathogenic potential. The pathogenic role of S. davidellisii highlights the importance of monitoring atypical Sporothrix infections in feline hosts, which may serve as environmental sentinels for emerging fungal pathogens. These findings expand the taxonomy of Sporothrix, contributing to our understanding of the evolutionary complexity and zoonotic potential of species within the S. pallida complex.

SUMMARYAlthough Scedosporium species and Lomentospora prolificans are uncommon causes of invasive fungal diseases (IFDs), these infections are associated with high mortality and are costly to treat with a limited armamentarium of antifungal drugs. In light of recent advances, including in the area of new antifungals, the present review provides a timely and updated overview of these IFDs, with a focus on the taxonomy, clinical epidemiology, pathogenesis and host immune response, disease manifestations, diagnosis, antifungal susceptibility, and treatment. An expansion of hosts at risk for these difficult-to-treat infections has emerged over the last two decades given the increased use of, and broader population treated with, immunomodulatory and targeted molecular agents as well as wider adoption of antifungal prophylaxis. Clinical presentations differ not only between genera but also across the different Scedosporium species. L. prolificans is intrinsically resistant to most currently available antifungal agents, and the prognosis of immunocompromised patients with lomentosporiosis is poor. Development of, and improved access to, diagnostic modalities for early detection of these rare mold infections is paramount for timely targeted antifungal therapy and surgery if indicated. New antifungal agents (e.g., olorofim, fosmanogepix) with novel mechanisms of action and less cross-resistance to existing classes, availability of formulations for oral administration, and fewer drug-drug interactions are now in late-stage clinical trials, and soon, could extend options to treat scedosporiosis/lomentosporiosis. Much work remains to increase our understanding of these infections, especially in the pediatric setting. Knowledge gaps for future research are highlighted in the review.

Past analysis of laboratory methods used for mycology specimens revealed significant variation in practices, many of which fell short of recommended procedures. In 2016 these findings led to a set of recommendations for laboratories to consider modification of their methods where appropriate, to analyse current laboratory methods used by participants in the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) Mycology module, and to compare these to the 2016 recommendations. Seven test items, with 105-107 participants each, were analysed. Several laboratories (7-12%) did not handle specimens as recommended in an appropriate biological safety cabinet. Direct microscopy was not performed on tissue specimens 23-25% of the time. The most used staining method was potassium hydroxide with an optical brightener for fluorescent microscopy (49%) followed by Gram stain (33%). While 17-25% of laboratories used three or more media, use of four or more was uncommon (<3%). Between 9-13% of participants used only a single non-inhibitory medium for cultures. Urine specimens were incubated longer than recommended with 57% of laboratories incubating for >7days and 24% >21 days. Duration of incubation was shorter than recommended for several specimen types with 36% of skin specimens and 37-48% of tissue specimens being kept ≤21 days. For cultures kept >7 days, 13% were inspected daily, but for those incubating >14 days only 3%. The methods of several laboratories remain outside recommended practice. An updated set of recommendations are made.

Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, but little is known about the contribution of different A. fumigatus strains to the development of different phenotypes and CLAD. We used multi-locus microsatellite typing (MLMT) to determine if there is a relationship between strain (i.e., genotype) and phenotype in 60 patients post LTx or with chronic respiratory disease across two time periods (1 November 2006–31 March 2009 and 1 November 2015–30 June 2017). The MLMT (STRAf) assay was highly discriminatory (Simpson’s diversity index of 0.9819–0.9942) with no dominant strain detected. No specific genotype–phenotype link was detected, but several clusters and related strains were associated with invasive aspergillosis (IA) and colonisation in the absence of CLAD. Host factors were linked to clinical phenotypes, with prior lymphopenia significantly more common in IA cases as compared with A. fumigatus-colonised patients (12/16 [75%] vs. 13/36 [36.1%]; p = 0.01), and prior Staphylococcus aureus infection was a significant risk factor for the development of IA (odds ratio 13.8; 95% confidence interval [2.01–279.23]). A trend toward a greater incidence of CMV reactivation post-A. fumigatus isolation was observed (0 vs. 5; p = 0.06) in LTx recipients. Further research is required to determine the pathogenicity and immunogenicity of specific A. fumigatus strains.

A German Shepherd Dog diagnosed with Rasamsonia argillacea based on fungal culture and DNA sequencing, is the first documented case in Australia, and the Southern Hemisphere This species is part of R. argillacea complex, which is an emerging concern in immunocompromised human and veterinary patients. Intraventricular brain hemorrhage, noted on MRI, has not been reported previously in a dog with fungal encephalitis. The patient was euthanized due to progression of clinical signs before a final diagnosis was made, so no treatment was attempted in this case.

Medically important pathogenic fungi invade vertebrate tissue and are considered primary when part of their nature life cycle is associated with an animal host and are usually able to infect immunocompetent hosts. Opportunistic fungal pathogens complete their life cycle in environmental habitats or occur as commensals within or on the vertebrate body, but under certain conditions can thrive upon infecting humans. The extent of host damage in opportunistic infections largely depends on the portal and modality of entry as well as on the host's immune and metabolic status. Diseases caused by primary pathogens and common opportunists, causing the top approximately 80% of fungal diseases [D. W. Denning, Lancet Infect Dis, 24:e428-e438, 2024, https://doi.org/10.1016/S1473-3099(23)00692-8], tend to follow a predictive pattern, while those by occasional opportunists are more variable. For this reason, it is recommended that diseases caused by primary pathogens and the common opportunists are named after the etiologic agent, for example, histoplasmosis and aspergillosis, while this should not be done for occasional opportunists that should be named as [causative fungus] [clinical syndrome], for example, Alternaria alternata cutaneous infection. The addition of a descriptor that identifies the location or clinical type of infection is required, as the general name alone may cover widely different clinical syndromes, for example, "rhinocerebral mucormycosis." A list of major recommended human and animal disease entities (nomenclature) is provided in alignment with their causative agents. Fungal disease names may encompass several genera of etiologic agents, consequently being less susceptible to taxonomic changes of the causative species, for example, mucormycosis covers numerous mucormycetous molds.

Background: Fungal keratitis is an ophthalmic emergency that can cause visual impairment and blindness. We reviewed the epidemiology and clinical features of fungal keratitis in a tropical Australian setting. Objectives: To document the clinical and microbiological characteristics of fungal keratitis in an Australian tropical setting. Methods: A retrospective cohort study of patients with fungal keratitis from October 2014 to December 2022 was conducted at Royal Darwin Hospital, Northern Territory, Australia. We reviewed all patients with culture-proven fungal keratitis and their outcomes. Results: There were 31 patients identified. Aboriginal and Torres Strait Islander (ATSI) patients were of a significantly younger median age (28 years) compared to non-ATSI patients (42 years), and they also presented later to health care. Contact lens use and ocular trauma were the most common predisposing factors. Most patients presented with a corneal infiltrate and corneal epithelial defect, and the central visual axis was affected in 54% of patients. Curvularia spp. and Fusarium spp. were the commonest causative fungi (39% and 30% respectively). Conclusions: Our series is different and reveals a wider range of fungal species identified over the 7 years of the study, in particular, a range of Curvularia spp. were detected. Access to eye health services in rural and remote settings is important, particularly for ATSI patients, as morbidity remains high.

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.

Recognising the growing global burden of fungal infections, the World Health Organization (WHO) established an advisory group consisting of experts in fungal diseases to develop a Fungal Priority Pathogen List. Pathogens were ranked based on their research and development needs and perceived public health importance using a series of global surveys and pathogen characteristics derived from systematic reviews. This systematic review evaluates the features and global impact of invasive disease caused by Candida glabrata (Nakaseomyces glabrata). PubMed and Web of Science were searched for studies reporting on mortality, morbidity (hospitalization and disability), drug resistance (including isolates from sterile and non-sterile sites, since these reflect the same organisms causing invasive infections), preventability, yearly incidence, diagnostics, treatability, and distribution/emergence in the last 10 years. Candida glabrata (N. glabrata) causes difficult-to-treat invasive infections, particularly in patients with underlying conditions such as immunodeficiency, diabetes, or those who have received broad-spectrum antibiotics or chemotherapy. Beyond standard infection prevention and control measures, no specific preventative measures have been described. We found that infection is associated with high mortality rates and that there is a lack of data on complications and sequelae. Resistance to azoles is common and well described in echinocandins-in both cases, the resistance rates are increasing. Candida glabrata remains mostly susceptible to amphotericin and flucytosine. However, the incidence of the disease is increasing, both at the population level and as a proportion of all invasive yeast infections, and the increases appear related to the use of antifungal agents.

Wastewater testing can inform public health action as a component of polio outbreak response. During 2022-2023, a total of 7 US jurisdictions (5 states and 2 cities) participated in prospective or retrospective testing of wastewater for poliovirus after a paralytic polio case was identified in New York state. Two distinct vaccine-derived poliovirus type 2 viruses were detected in wastewater from New York state and New York City during 2022, representing 2 separate importation events. Of those viruses, 1 resulted in persistent community transmission in multiple New York counties and 1 paralytic case. No poliovirus was detected in the other participating jurisdictions (Connecticut, New Jersey, Michigan, and Illinois and Chicago, IL). The value of routine wastewater surveillance for poliovirus apart from an outbreak is unclear. However, these results highlight the ongoing risk for poliovirus importations into the United States and the need to identify undervaccinated communities and increase vaccination coverage to prevent paralytic polio.

Earlier this year we published an overview of taxonomic changes for medically relevant yeasts and molds [1], which is a heavily debated issue given the many changes currently impacting diagnostic laboratories.We are grateful to Dr. Denning for his comments on this article, and while we attempted to cover a wide range of issues around fungal nomenclature change, we agree that there remains a need to consider the nomenclature of disease manifestations caused by fungi, which are frequently named for the causative taxa [2].For example, can the disease term 'candidemia' be applied to blood stream infections caused by Nakaseomyces glabratus (formerly Candida glabrata) or Clavispora lusitaniae (formerly Candida lusitaniae)?And similarly, does the term fusariosis still apply to infections caused by Bisifusarium dimerum (formerly Fusarium dimerum) or Neocosmospora solani (formerly Fusarium solani)?Where therapeutic guidelines, drug licenses, and formulary indications utilize such terminology, is there potential for patients to

Background New and emerging risks for invasive aspergillosis (IA) bring the need for contemporary analyses of the epidemiology and outcomes of IA, in order to improve clinical practice.Methods The study was a retrospective, multicenter, cohort design of proven and probable IA in adults from 10 Australasian tertiary centres (January 2017-December 2020). Descriptive analyses were used to report patients' demographics, predisposing factors, mycological characteristics, diagnosis and management. Accelerated failure-time model was employed to determine factor(s) associated with 90-day all-cause mortality (ACM).Findings Of 382 IA episodes, 221 (in 221 patients) fulfilled inclusion criteria - 53 proven and 168 probable IA. Median patient age was 61 years (IQR 51-69). Patients with haematologic malignancies (HM) comprised 49.8% of cases. Fifteen patients (6.8%) had no pre-specified immunosuppression and eleven patients (5.0%) had no documented comorbidity. Only 30% of patients had neutropenia. Of 170 isolates identified, 40 (23.5%) were identified as non-Aspergillus fumigatus species complex. Azole-resistance was present in 3/46 (6.5%) of A. fumigatus sensu stricto isolates. Ninety-day ACM was 30.3%. HM (HR 1.90; 95% CI 1.04-3.46, p = 0.036) and ICU admission (HR 4.89; 95% CI 2.93-8.17, p < 0.001) but not neutropenia (HR 1.45; 95% CI 0.88-2.39, p = 0.135) were associated with mortality. Chronic kidney disease was also a significant predictor of death in the HM subgroup (HR 3.94; 95% CI 1.15-13.44, p = 0.028).Interpretation IA is identified in high number of patients with mild/no immunosuppression in our study. The relatively high proportion of non -A. fumigatus species complex isolates and 6.5% azole-resistance rate amongst A. fumigatus sensu stricto necessitates accurate species identification and susceptibility testing for optimal patient outcomes.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BackgroundInvasive fungal infections cause millions of infections annually, but diagnosis remains challenging. There is an increased need for low-cost, easy to use, highly sensitive and specific molecular assays that can differentiate between colonized and pathogenic organisms from different clinical specimens.Areas coveredWe reviewed the literature evaluating the current state of molecular diagnostics for invasive fungal infections, focusing on current and novel molecular tests such as polymerase chain reaction (PCR), digital PCR, high-resolution melt (HRM), and metagenomics/next generation sequencing (mNGS).Expert opinionPCR is highly sensitive and specific, although performance can be impacted by prior/concurrent antifungal use. PCR assays can identify mutations associated with antifungal resistance, non-Aspergillus mold infections, and infections from endemic fungi. HRM is a rapid and highly sensitive diagnostic modality that can identify a wide range of fungal pathogens, including down to the species level, but multiplex assays are limited and HRM is currently unavailable in most healthcare settings, although universal HRM is working to overcome this limitation. mNGS offers a promising approach for rapid and hypothesis-free diagnosis of a wide range of fungal pathogens, although some drawbacks include limited access, variable performance across platforms, the expertise and costs associated with this method, and long turnaround times in real-world settings.