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Elizabeth L Berkow, Shawn R Lockhart Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Candida albicans and the emerging non-albicans Candida spp. have significant clinical relevance among many patient populations. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of these infections, but it is only fungistatic against Candida spp. and both inherent and acquired resistance to fluconazole have been reported. Such mechanisms of resistance include increased drug efflux, alteration or increase in the drug target, and development of compensatory pathways for producing the target sterol, ergosterol. While many mechanisms of resistance observed in C. albicans are also found in the non-albicans species, there are also important and unexpected differences between species. Furthermore, mechanisms of fluconazole resistance in emerging Candida spp., including the global health threat Candida auris, are largely unknown. In order to preserve the utility of one of our fundamental antifungal drugs, fluconazole, it is essential that we fully appreciate the manner by which Candida spp. manifest resistance to it. Keywords: Candida, fluconazole resistance, ERG11, drug efflux, ergosterol

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.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jason Zucker reports support from the National Institutes of Health and receipt of honoraria from academic medical centers or educational centers for educational lectures. Shauna H. Gunaratne reports receipt of honoraria from the International Antiviral Society-USA for an invited review and from the New York State Department of Health AIDS Institute for work on guidelines. John G. Zampella reports receipt of honoraria from the Vaseline Healing Project and compensated participation on advisory boards (Merck, Ferndale Pharma Group, Janssen, and Dermavant), service as deputy chair of the American Academy of Dermatology State Society Relationship Committee, and co-chair of the American Academy of Dermatology LGBTQ Expert Research Group. No other potential conflicts of interest were disclosed.

Objectives: Reported amphotericin B resistance rates for Candida auris vary considerably. This may reflect clinically relevant differences in susceptibility, technical issues with testing, or adoption of a clinical breakpoint that bisects the wild-type population. We compared reference methods and two gradient diffusion strips using a shared C. auris strain collection., Methods: Forty C. auris strains from nine U.S. states and ≥3 clades were included. Fourteen MIC data sets were generated using European Committee on Antimicrobial Susceptibility Testing (EUCAST) E.Def 7.4, Clinical and Laboratory Standards Institute (CLSI) M27Ed4, Etest, and MIC gradient test strip (MTS, Liofilchem) MICs. MICs ≤1 mg/L were classified as susceptible., Results: EUCAST and CLSI amphotericin B MIC testing were robust across the included method variables. The modal MIC was 1 mg/L, distributions unimodal and narrow with similar geometric mean (GM)-MICs (0.745-1.072); however, susceptibility classification varied (0-28% resistance). Gradient diffusion strip testing resulted in wider and bimodal distributions for 8/9 data sets. If adopting, per manufacturer's protocol, double inoculation for the Etest method, the modal MIC increased to 2-4 mg/L and resistance rates to 45-63% versus 25-30% with the single inoculation. The EUCAST, CLSI, Etest, and MTS strip MICs correlated to the optical density of drug-free control EUCAST wells, suggesting that some isolates grew better than others and that this was associated with MIC., Discussion: The EUCAST and CLSI MIC results were in close agreement, whereas the strip test showed wider and bimodal distributions with reader to reader and centre to centre variation. Our study adds to the concern for commercial MIC testing of amphotericin B against C. auris and suggests the current breakpoint leads to random susceptibility classification., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.)

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021-2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Antifungal-resistant dermatophyte infections have recently emerged as a global public health concern. A survey of US infectious diseases specialists found that only 65% had heard of this issue and just 39% knew how to obtain testing to determine resistance. Increased clinician awareness and access to testing for antifungal-resistant dermatophytosis are needed.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for Ortho-Dermatologics, Moberg Pharmaceuticals, Eli Lilly, and BelleTorus Corporation. Authors Zarzeka, Benedict, and McCloskey, Drs Lockhart and Gold have no conflicts of interest to declare.

The taxonomy of the Cryptococcus gattii species complex continues to evolve, and has been divided into five pathogenic species. The objective of this systematic review was to summarise the geographical distribution of the C gattii species complex and the species within the C gattii species complex. We searched PubMed for articles related to human, animal, ecological, or laboratory-based studies of C gattii species complex isolates with traceable geographical origin published from January, 1970, until September, 2021. Having extracted their geographical origin, we used ArcMap to construct maps according to the highest degree of resolution allowed by their reported taxonomy, to reflect the most likely area of transmission on the basis of published reports of human isolates. 604 such articles were included in the study. This review indicated that although C gattii species complex isolates have been reported globally, understanding their heterogeneous geographical distribution by species can have implications for researchers and clinicians in formulating research questions and considering diagnostic quandaries., Competing Interests: Declaration of interests FH is the Vice President of the International Society for Human and Animal Mycology, treasurer of the Netherlands Society for Medical Mycology, chair of the Royal Netherlands Society for Microbiology, Microbial Genomic Division, and received molecular diagnostic kits from Bruker Molecular Diagnostics. NCB was the Data and Safety Monitoring Board chair for NCT04335123. All other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Blastomycosis, coccidioidomycosis, and histoplasmosis are environmentally acquired fungal diseases that clinically resemble bacterial and viral community-acquired pneumonia and require laboratory testing for diagnosis. Patients frequently present to primary care and experience diagnostic delays when a fungal etiology is not initially suspected. Current national-level public health surveillance for these diseases is limited and does not include laboratory data, so nationwide testing practices are unknown., Methods: We identified laboratory tests for blastomycosis, coccidioidomycosis, and histoplasmosis ordered during 1 March 2019-29 February 2024 and performed within a major national commercial laboratory system. We analyzed test results, patient and healthcare provider features, reasons for testing, and temporal trends., Results: Results included 5693 Blastomyces complement fixation tests (of those, 12% were positive), 71 858 immunodiffusion tests (0.1% positive), and 1186 serum enzyme immunoassay (EIA) tests (11% positive); 154 989 Coccidioides EIA immunoglobulin M results (5% positive) and 154 968 immunoglobulin G results (8% positive); and 46 346 Histoplasma complement fixation tests (30% positive), 49 062 immunodiffusion tests (1% positive), 35 506 serum EIA tests (4% positive), and 82 489 urine EIA tests (2% positive). Most histoplasmosis (58%-74%) and blastomycosis (42%-68%) tests were ordered from hospitals, whereas coccidioidomycosis tests were most frequently ordered by primary care providers (40%). A yearly average of 2727 positive tests were ordered by healthcare providers in states without public health surveillance for these diseases., Conclusions: Blastomycosis, coccidioidomycosis, and histoplasmosis are likely underdetected in primary care settings or by public health surveillance. Increased testing by primary care providers and expanded surveillance are needed to reduce disease burden., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Between September and November 2021, 5 snow leopards ( Panthera uncia ) and 1 lion ( Panthera leo ) were naturally infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) and developed progressive respiratory disease that resulted in death. Severe acute respiratory syndrome coronavirus 2 sequencing identified the delta variant in all cases sequenced, which was the predominant human variant at that time. The time between initial clinical signs and death ranged from 3 to 45 days. Gross lesions in all 6 cats included nasal turbinate hyperemia with purulent discharge and marked pulmonary edema. Ulcerative tracheitis and bronchitis were noted in 4 cases. Histologically, there was necrotizing and ulcerative rhinotracheitis and bronchitis with fibrinocellular exudates and fibrinosuppurative to pyogranulomatous bronchopneumonia. The 4 cats that survived longer than 8 days had fungal abscesses. Concurrent bacteria were noted in 4 cases, including those with more acute disease courses. Severe acute respiratory syndrome coronavirus 2 was detected by in situ hybridization using probes against SARS-CoV-2 spike and nucleocapsid genes and by immunohistochemistry. Viral nucleic acid and protein were variably localized to mucosal and glandular epithelial cells, pneumocytes, macrophages, and fibrinocellular debris. Based on established criteria, SARS-CoV-2 was considered a contributing cause of death in all 6 cats. While mild clinical infections are more common, these findings suggest that some SARS-CoV-2 variants may cause more severe disease and that snow leopards may be more severely affected than other felids., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission., Objective: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing., Design, Setting, and Participants: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers., Main Outcome and Measure: Improvement or resolution at the last follow-up assessment., Results: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 μg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates., Conclusion and Relevance: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

Background: Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention., Methods: Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data., Results: Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates ( P = .01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates., Conclusions: Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis . Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis ., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Dermatophytoses are fungal infections of the skin, hair, and nails that affect approximately 25% of the global population. Occlusive clothing, living in a hot humid environment, poor hygiene, proximity to animals, and crowded living conditions are important risk factors. Dermatophyte infections are named for the anatomic area they infect, and include tinea corporis, cruris, capitis, barbae, faciei, pedis, and manuum. Tinea incognito describes steroid-modified tinea. In some patients, especially those who are immunosuppressed or who have a history of corticosteroid use, dermatophyte infections may spread to involve extensive skin areas, and, in rare cases, may extend to the dermis and hair follicle. Over the past decade, dermatophytoses cases not responding to standard of care therapy have been increasingly reported. These cases are especially prevalent in the Indian subcontinent, and Trichophyton indotineae has been identified as the causative species, generating concern regarding resistance to available antifungal therapies. Antifungal-resistant dermatophyte infections have been recently recognized in the United States. Antifungal resistance is now a global health concern. When feasible, mycological confirmation before starting treatment is considered best practice. To curb antifungal-resistant infections, it is necessary for physicians to maintain a high index of suspicion for resistant dermatophyte infections coupled with antifungal stewardship efforts. Furthermore, by forging partnerships with federal agencies, state and local public health agencies, professional societies, and academic institutions, dermatologists can lead efforts to prevent the spread of antifungal-resistant dermatophytes., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

We describe a feline sporotrichosis cluster and zoonotic transmission between one of the affected cats and a technician at a veterinary clinic in Kansas, USA. Increased awareness of sporotrichosis and the potential for zoonotic transmission could help veterinary professionals manage feline cases and take precautions to prevent human acquisition.

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51 , corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus . SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates., Competing Interests: The authors declare no conflict of interest.

CHROMagar Candida Plus is a new formulation of chromogenic media designed for the detection and differentiation of major clinical Candida species, including Candida auris . The objective of this study is to evaluate CHROMagar Candida Plus when used according to manufacturer's instructions with a panel of 206 fungal isolates and 83 skin-swab specimens originally collected for C. auris colonization screening. Of the 68 C . auris isolates tested, 66/68 displayed the expected light-blue colony morphology and blue halo within 48 h. None of the remaining 138 non- auris isolates appeared similar to C. auris . CHROMagar Candida Plus was, therefore, inclusive to 97% of 68 C . auris isolates tested and supported visual exclusion of 100% of the 138 non- C . auris isolates tested. For the 83 colonization screening specimens, direct plating onto CHROMagar Candida Plus was 60% sensitive and 100% specific when compared to the enrichment broth gold-standard reference method. In sum, these findings demonstrate the utility of this media when working with isolates but also notable limitations when working with primary skin-swabs specimens when competing yeast species are present.IMPORTANCE Candida auris is an emerging fungal pathogen of public health concern. As it continues to spread, it is important to publish evaluations of new diagnostic tools. In this study, we share our experience with a new chromogenic media which can help distinguish C. auris from related species., Competing Interests: The authors declare no conflict of interest.

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

Background: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology., Methods: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates., Findings: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade., Interpretation: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country., Funding: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil., Competing Interests: Declaration of interests We declare no competing interests., (Published by Elsevier Ltd.)

Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission , or acquired resistance. IMPORTANCE In our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo ., Competing Interests: The authors declare no conflict of interest.

Dermatophyte infections (a.k.a. ringworm, tinea) affect an estimated 20%-25% of the world's population. In North America, most dermatophytoses are caused by Trichophyton rubrum or Trichophyton mentagrophytes species complexes. Severe and antifungal-resistant dermatophytoses are a growing global public health problem. A new species of the T. mentagrophytes species complex, Trichophyton indotineae , has recently emerged and is notable for the severe infections it causes, its propensity for antifungal resistance, and its global spread. In this issue of the Journal of Clinical Microbiology , C. F. Cañete-Gibas, J. Mele, H. P. Patterson, et al. (J Clin Microbiol 61:e00562-23, 2023, https://doi.org/10.1128/JCM.00562-23) summarize the results of speciation and AFST performed on North American dermatophyte isolates received at a fungal diagnostic reference laboratory. Within their collection, 18.6% of isolates were resistant to terbinafine (a first-line oral antifungal for dermatophytoses), and similar proportions of T. rubrum and T. indotineae demonstrated terbinafine resistance. The authors also found that T. indotineae has been present in North America since at least 2017. These findings highlight the importance of increased surveillance efforts to monitor trends in severe and antifungal-resistant dermatophytoses and the need for antifungal stewardship efforts, the success of which is contingent upon improving laboratory capacity for dermatophyte speciation and AFST., Competing Interests: The authors declare no conflict of interest.

During recent decades, the emergence of pathogenic fungi has posed an increasing public health threat, particularly given the limited number of antifungal drugs available to treat invasive infections. In this Review, we discuss the global emergence and spread of three emerging antifungal-resistant fungi: Candida auris, driven by global health-care transmission and possibly facilitated by climate change; azole-resistant Aspergillus fumigatus, driven by the selection facilitated by azole fungicide use in agricultural and other settings; and Trichophyton indotineae, driven by the under-regulated use of over-the-counter high-potency corticosteroid-containing antifungal creams. The diversity of the fungi themselves and the drivers of their emergence make it clear that we cannot predict what might emerge next. Therefore, vigilance is critical to monitoring fungal emergence, as well as the rise in overall antifungal resistance., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way., Competing Interests: The authors declare no conflict of interest.

Candida auris has been recognized as an emerging multidrug-resistant pathogen with a significant public health burden, causing cases of invasive infection and colonization due to its persistence on inanimate surfaces, ability to colonize skin of some patients, and high transmissibility in healthcare settings. The first sporadic report of the isolation of this species from the ear canal of a patient in Asia was in 2009 and reports from other regions of the world soon followed. However, it was not until 2015 that global epidemiological alerts were communicated as a result of an increasing number of reports of invasive infections caused by C. auris in several countries. Colombia was soon added to this list in 2016 after an unusual increase in the number of C. haemulonii isolates was reported, later confirmed as C. auris. Since the issuing of a national alert by the Colombian National Institute of Health together with the Ministry of Health in 2016, the number of cases reported reached over 2,000 by 2022. Colombian isolates have not shown pan resistance to available antifungals, unlike C. auris strains reported in other regions of the world, which leaves patients in Colombia with therapeutic options for these infections. However, increasing fluconazole resistance is being observed. Whole-genome sequencing of Colombian C. auris isolates has enhanced molecular epidemiological data, grouping Colombian isolates in clade IV together with other South American isolates.

Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines. Characterizing the public health, economic, health system, and individual burden caused by fungal diseases can provide critical insights to promote better prevention and treatment. The development and validation of fungal diagnostic tests that are rapid, accurate, and cost-effective can improve testing practices. Understanding best practices for antifungal prophylaxis can optimize prevention in at-risk populations, while research on antifungal resistance can improve patient outcomes. Investment in vaccines may eliminate certain fungal diseases or lower incidence and mortality. Public health research priorities and approaches may vary by fungal pathogen.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for BelleTorus Corporation, Ortho-dermatologics, Moberg Pharmaceuticals, and Hoth Therapeutics. Dr Gold, Author Benedict, and Dr Lockhart have no conflicts of interest to declare.

Competing Interests: Conflicts of interest Dr Lipner has served as a consultant for BelleTorus Corporation, Hoth Therapeutics, Moberg Pharmaceuticals, and Ortho-dermatologics. Dr Gold, Author Smith, Author Benedict, and Dr Lockhart have no conflicts of interest to declare.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Competing Interests: Dr Lipner has served as a consultant for BelleTorus Corporation and Ortho-dermatologics.

Candida haemulonii complex species can be multidrug-resistant and cause infections such as candidemia. This study determined the genetic relationship between isolates from Brazil and the United States through whole-genome sequencing and performed antifungal susceptibility testing to investigate drug resistance. Contrary to what is widely described, most isolates were susceptible to azoles. However, an atypical susceptibility profile was found in 50% of Candida pseudohaemulonii strains, including resistance to the three echinocandins. Isolates from both countries formed distinct clusters with wide genetic diversity. Isolates from three hospitals in Brazil were clonal and involved in candidemia cases, pointing to the importance of improving hospital infection control measures and molecular identification., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Candida auris is an emerging fungal threat that has been spreading in the United States since it was first reported in 2016., Objective: To describe recent changes in the U.S. epidemiology of C auris occurring from 2019 to 2021., Design: Description of national surveillance data., Setting: United States., Patients: Persons with any specimen that was positive for C auris ., Measurements: Case counts reported to the Centers for Disease Control and Prevention by health departments, volume of colonization screening, and antifungal susceptibility results were aggregated and compared over time and by geographic region., Results: A total of 3270 clinical cases and 7413 screening cases of C auris were reported in the United States through 31 December 2021. The percentage increase in clinical cases grew each year, from a 44% increase in 2019 to a 95% increase in 2021. Colonization screening volume and screening cases increased in 2021 by more than 80% and more than 200%, respectively. From 2019 to 2021, 17 states identified their first C auris case. The number of C auris cases that were resistant to echinocandins in 2021 was about 3 times that in each of the previous 2 years., Limitation: Identification of screening cases depends on screening that is done on the basis of need and available resources. Screening is not conducted uniformly across the United States, so the true burden of C auris cases may be underestimated., Conclusion: C auris cases and transmission have risen in recent years, with a dramatic increase in 2021. The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris . These findings highlight the need for improved detection and infection control practices to prevent spread of C auris ., Primary Funding Source: None.

Scedosporium spp. and Lomentospora prolificans are an emerging group of fungi refractory to current antifungal treatments. These species largely affect immunocompromised individuals but can also be lung colonizers in cystic fibrosis patients. Although Scedosporium apiospermum is thought to be the predominant species, the group has been expanded to a species complex. The distribution of species within the S. apiospermum species complex and other closely related species in the United States is largely unknown. Here, we used β-tubulin and ITS sequences to identify 37 Scedosporium isolates to the species level. These Scedosporium isolates as well as 13 L. prolificans isolates were tested against a panel of nine antifungal drugs, including the first in novel class orotimide, olorofim. IMPORTANCE Scedosporium and Lomentospora infections are notoriously hard to treat as these organisms can be resistant to numerous antifungals. The manuscript contributes to our knowledge of the activity of the new antifungal agent olorofim and comparator agents against Lomentospora and against Scedosporium isolates that have been molecularly identified to the species level. The efficacy of olorofim against all species of Scedosporium and Lomentospora was confirmed.

Azole resistance in Aspergillus fumigatus is a One Health resistance threat, where azole fungicide exposure compromises the efficacy of medical azoles. The use of the recently authorized fungicide ipflufenoquin, which shares its mode-of-action with a new antifungal olorofim, underscores the need for risk assessment for dual use of antifungals., Competing Interests: Declaration of Competing Interest Paul E Verweij declares grants from F2G and Gilead Sciences and payments for lectures and advisory boards by F2G, Gilead Sciences, Pfizer and Mundipharma. All payments to institute. Maiken C Arendrup, Ana Alastruey-Izquierdo, Jeremy A W Gold, Shawn R Lockhart, and Tom Chiller declare no competing interests. P Lewis White declares grants from F2G, CERBA, IHMA, payments for lectures and advisory boards by F2G, Gilead Sciences, and Pfizer, and support for travel from OLM., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Candidemia is a common healthcare-associated infection with high mortality. Estimates of recurrence range from 1% to 17%. Few studies have focused on those with recurrent candidemia, who often experience more severe illness and greater treatment failure. We describe recurrent candidemia trends and risk factors., Methods: We analyzed population-based candidemia surveillance data collected during 2011-2018. Persons with >1 episode (defined as the 30-day period after a positive Candida species) were classified as having recurrent candidemia. We compared factors during the initial episode between those who developed recurrent candidemia and those who did not., Results: Of the 5428 persons identified with candidemia, 326 (6%) had recurrent infection. Recurrent episodes occurred 1.0 month to 7.6 years after any previous episode. In multivariable logistic regression controlling for surveillance site and year, recurrent candidemia was associated with being 19-44 years old (vs ≥65 years; adjusted odds ratio [aOR], 3.05 [95% confidence interval {CI}, 2.10-4.44]), being discharged to a private residence (vs medical facility; aOR, 1.53 [95% CI, 1.12-2.08]), hospitalization in the 90 days prior to initial episode (aOR, 1.66 [95% CI, 1.27-2.18]), receipt of total parenteral nutrition (aOR, 2.08 [95% CI, 1.58-2.73]), and hepatitis C infection (aOR, 1.65 [95% CI, 1.12-2.43])., Conclusions: Candidemia recurrence >30 days after initial infection occurred in >1 in 20 persons with candidemia. Associations with younger age and hepatitis C suggest injection drug use may play a modifiable role. Prevention efforts targeting central line care and total parenteral nutrition use may help reduce the risk of recurrent candidemia., Competing Interests: Potential conflicts of interest. Monica M. Farley reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement, NIH grant to institution for the Infectious Diseases Clinical Research Consortium (IDCRC) Leadership Group (unrelated to this project), honoraria for Grand Rounds presentation at NYU in January 2022 (unrelated to this project), and serves in a leadership role on the National Foundation for Medical Research Finance Committee (unrelated to this project). Lee H. Harrison reports support for attending meetings and/or travel from GSK and participation on a Data Safety Monitoring Board or Advisory Board (Merck). William Schaffner reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement and serves as Medical Director for National Foundation for Infectious Diseases outside the submitted work. Tiffanie M. Markus reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program cooperative agreement. Rebecca A. Pierce reports institutional support from the Centers for Disease Control and Prevention via the Emerging Infections Program and Epidemiology and Laboratory Capacity cooperative agreements. All other authors report no conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against Candida spp. Loewe additivity-based fractional inhibitory concentration index (FICi) analysis and Bliss independence-based response surface (BIRS) analysis were used to analyze two-drug inter- and intraclass combinations of triazoles (AZO) (voriconazole, posaconazole), echinocandins (ECH) (caspofungin, micafungin, anidulafungin), and a polyene (amphotericin B) against Candida albicans, C. parapsilosis, and C. glabrata. Although mean FIC indices did not differ statistically significantly from the additivity range of 0.5−4, indicating no significant pharmacodynamic interactions for all of the strain−combinations tested, BIRS analysis showed that significant pharmacodynamic interactions with the sum of percentages of interactions determined with this analysis were strongly associated with the FIC indices (Χ2 646, p < 0.0001). Using a narrower additivity range of 1−2 FIC index analysis, statistically significant pharmacodynamic interactions were also found with FICi and were in agreement with those found with BIRS analysis. All ECH+AB combinations were found to be synergistic against all Candida strains except C. glabrata. For the AZO+AB combinations, synergy was found mostly with the POS+AB combination. All AZO+ECH combinations except POS+CAS were synergistic against all Candida strains although with variable magnitude; significant antagonism was found for the POS+MIF combination against C. albicans. The AZO+AZO combination was additive for all strains except for a C. parapsilosis strain for which antagonism was also observed. The ECH+ECH combinations were synergistic for all Candida strains except C. glabrata for which they were additive; no antagonism was found.

Identification of the emerging multidrug-resistant yeast Candida auris is challenging. Here, we describe the role of the Mexico national reference laboratory Instituto de Diagnóstico y Referencia Epidemiológicos Dr. Manuel Martínez Báez (InDRE) and the Mexican national laboratory network in the identification of C. auris. Reference identification of six suspected isolates was done based on phenotypic and molecular laboratory methods, including growth in special media, evaluation of isolate micromorphology, and species-specific PCR and pan-fungal PCR and sequencing. The four C. auris isolates identified were able to grow on modified Sabouraud agar with 10% NaCl incubated at 42 °C. With one exception, isolates of C. auris were spherical to ovoid yeast-like cells and blastoconidia, with no hyphae or pseudohyphae on cornmeal agar. C. auris isolates were resistant to fluconazole. Species-specific and pan-fungal PCR confirmed isolates as C. auris. Sequence analysis revealed the presence of two different C. auris clades in Mexico, clade I (South Asia) and clade IV (South America)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We report a fatal infection in a 65-year-old immunocompromised male patient caused by pan-triazole-resistant Aspergillus fumigatus containing a TR 34 /L98H genetic mutation linked to agricultural fungicide use. Clinical and environmental surveillance of triazole-resistant A. fumigatus is needed in the United States to prevent spread and guide healthcare and agricultural practices.

Candida auris is an emerging yeast species that has the unique characteristics of patient skin colonization and rapid transmission within health care facilities and the ability to rapidly develop antifungal resistance. When C. auris first started to appear in clinical microbiology laboratories, it could be identified only by using DNA sequencing. In the decade since its first identification outside of Japan, there have been many improvements in the detection of C. auris. These include the expansion of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) databases to include C. auris, the development of both laboratory-developed tests and commercially available kits for its detection, and special CHROMagar for identification from laboratory specimens. Here we discuss the current tools and resources that are available for C. auris identification and detection.

Background: Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system., Methods: During 2017-2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases., Results: Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n = 66 [63.5%]), mucormycosis (n = 8 [7.7%]), and fusariosis (n = 4 [3.8%]); the most frequently affected body sites were pulmonary (n = 66 [63.5%]), otorhinolaryngologic (n = 17 [16.3%]), and cutaneous/deep tissue (n = 9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit-level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients., Conclusions: IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis., Methods: We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention's Emerging Infections Program during April-August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher's exact tests., Results: Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit-level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%)., Conclusions: One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Candida and Cryptococcus affect millions of people yearly, being responsible for a wide array of clinical presentations, including life-threatening diseases. Interestingly, most human pathogenic yeasts are not restricted to the clinical setting, as they are also ubiquitous in the environment. Recent studies raise concern regarding the potential impact of agricultural use of azoles on resistance to medical antifungals in yeasts, as previously outlined with Aspergillus fumigatus. Thus, we undertook a narrative review of the literature and provide lines of evidence suggesting that an alternative, environmental route of azole resistance, may develop in pathogenic yeasts, in addition to patient route. However, it warrants sound evidence to support that pathogenic yeasts cross border between plants, animals and humans and that environmental reservoirs may contribute to azole resistance in Candida or other yeasts for humans. As these possibilities could concern public health, we propose a road map for future studies under the One Health perspective., (© 2021 Wiley-VCH GmbH.)