Medicine › Infectious Diseases

Antifungal resistance and susceptibility

Works Count: 97928

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Description

This cluster of papers covers the diagnosis, management, epidemiology, and treatment of various fungal infections such as candidiasis, aspergillosis, mucormycosis, and biofilm-related infections. It also discusses antifungal therapy, resistance mechanisms, and the impact of these infections on immunocompromised patients.

Keywords

Invasive Fungal Infections; Candidiasis; Aspergillosis; Antifungal Therapy; Mucormycosis; Biofilm Formation; Antifungal Resistance; Epidemiology; Immunocompromised Patients; Diagnostic Methods

Posaconazole or Fluconazole for Prophylaxis in Severe Graft-versus-Host Disease

2007-01-25

Andrew J. Ullmann , Jeffrey H. Lipton , David H. Vesole +7 more

Invasive fungal infections are an important cause of morbidity and mortality after allogeneic hematopoietic stem-cell transplantation. Invasive fungal infections are an important cause of morbidity and mortality after allogeneic hematopoietic stem-cell transplantation.

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Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia

2007-01-25

Oliver A. Cornely , Johan Maertens , Drew J. Winston +7 more

Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections. Patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or the myelodysplastic syndrome are at high risk for difficult-to-treat and often fatal invasive fungal infections.

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Virulence factors of Candida albicans

2001-07-01

Richard Calderone , William A. Fonzi

Nonfilamentous C. albicans Mutants Are Avirulent

1997-09-01

Hsiu‐Jung Lo , Julia R. Köhler , Beth DiDomenico +3 more

Immunity to fungal infections

2011-03-11

Luigina Romani

Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis

2002-12-18

Jorge Mora-Duarte , Robert F. Betts , Coleman Rotstein +7 more

Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis.We … Caspofungin is an echinocandin agent with fungicidal activity against candida species. We performed a double-blind trial to compare caspofungin with amphotericin B deoxycholate for the primary treatment of invasive candidiasis.We enrolled patients who had clinical evidence of infection and a positive culture for candida species from blood or another site. Patients were stratified according to the severity of disease, as indicated by the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the presence or absence of neutropenia and were randomly assigned to receive either caspofungin or amphotericin B. The study was designed to compare the efficacy of caspofungin with that of amphotericin B in patients with invasive candidiasis and in a subgroup with candidemia.Of the 239 patients enrolled, 224 were included in the modified intention-to-treat analysis. Base-line characteristics, including the percentage of patients with neutropenia and the mean APACHE II score, were similar in the two treatment groups. A modified intention-to-treat analysis showed that the efficacy of caspofungin was similar to that of amphotericin B, with successful outcomes in 73.4 percent of the patients treated with caspofungin and in 61.7 percent of those treated with amphotericin B (difference after adjustment for APACHE II score and neutropenic status, 12.7 percentage points; 95.6 percent confidence interval, -0.7 to 26.0). An analysis of patients who met prespecified criteria for evaluation showed that caspofungin was superior, with a favorable response in 80.7 percent of patients, as compared with 64.9 percent of those who received amphotericin B (difference, 15.4 percentage points; 95.6 percent confidence interval, 1.1 to 29.7). Caspofungin was as effective as amphotericin B in patients who had candidemia, with a favorable response in 71.7 percent and 62.8 percent of patients, respectively (difference, 10.0 percentage points; 95.0 percent confidence interval, -4.5 to 24.5). There were significantly fewer drug-related adverse events in the caspofungin group than in the amphotericin B group.Caspofungin is at least as effective as amphotericin B for the treatment of invasive candidiasis and, more specifically, candidemia.

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Antifungal agents: mechanisms of action

2003-05-19

Frank C. Odds , Alistair J. P. Brown , Neil A. R. Gow

Isolation of the Candida albicans gene for orotidine-5′-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations

1984-12-01

Amanda M. Gillum , Emma Y. H. Tsay , Donald R. Kirsch

Biological effects of cyclosporin A: A new antilymphocytic agent

1976-07-01

J. F. Borel , Camille Feurer , H. U. Gubler +1 more

Voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis

2002-08-08

Raoul Herbrecht , David W. Denning , Thomas F. Patterson +7 more

Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis.

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Epidemiology and Outcome of Mould Infections in Hematopoietic Stem Cell Transplant Recipients

2002-04-01

Kieren A. Marr , Rachel A. Carter , Fulvio Crippa +2 more

Reports have focused on the emergence of moulds as pathogens in recipients of hematopoietic stem cell transplants. To review the incidence of and risks for mould infections, we examined the … Reports have focused on the emergence of moulds as pathogens in recipients of hematopoietic stem cell transplants. To review the incidence of and risks for mould infections, we examined the records of 5589 patients who underwent hematopoietic stem cell transplantation at the Fred Hutchinson Cancer Research Center (Seattle) from 1985 through 1999. After 1992, the incidence of invasive aspergillosis increased in allograft recipients and remained high through the 1990s. Infections with non-fumigatus Aspergillus species, Fusarium species, and Zygomycetes increased during the late 1990s, especially in patients who received multiple transplants. Although infection caused by Scedosporium species was common in patients who had neutropenia, infection caused by Zygomycetes typically occurred later after transplantation, when patients had graft-versus-host disease. The overall 1-year survival rate was equally poor (∼20%) for all patients with mould infections. The results of the present study demonstrate the changing epidemiology of mould infections, emphasizing the increasing importance of amphotericin B–resistant organisms and the differences in risks and outcome of infection with different filamentous fungi.

Aspergillosis Case-Fatality Rate: Systematic Review of the Literature

2001-02-01

Swu‐Jane Lin , Jennifer Schranz , Steven M. Teutsch

To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort … To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of ⩾10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.

Echinocandin antifungal drugs

2003-10-01

David W. Denning

Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance

1998-04-01

Theodore C. White , Kieren A. Marr , Raleigh A. Bowden

In the past decade, the frequency of diagnosed fungal infections has risen sharply due to several factors, including the increase in the number of immunosuppressed patients resulting from the AIDS … In the past decade, the frequency of diagnosed fungal infections has risen sharply due to several factors, including the increase in the number of immunosuppressed patients resulting from the AIDS epidemic and treatments during and after organ and bone marrow transplants. Linked with the increase in fungal infections is a recent increase in the frequency with which these infections are recalcitrant to standard antifungal therapy. This review summarizes the factors that contribute to antifungal drug resistance on three levels: (i) clinical factors that result in the inability to successfully treat refractory disease; (ii) cellular factors associated with a resistant fungal strain; and (iii) molecular factors that are ultimately responsible for the resistance phenotype in the cell. Many of the clinical factors that contribute to resistance are associated with the immune status of the patient, with the pharmacology of the drugs, or with the degree or type of fungal infection present. At a cellular level, antifungal drug resistance can be the result of replacement of a susceptible strain with a more resistant strain or species or the alteration of an endogenous strain (by mutation or gene expression) to a resistant phenotype. The molecular mechanisms of resistance that have been identified to date in Candida albicans include overexpression of two types of efflux pumps, overexpression or mutation of the target enzyme, and alteration of other enzymes in the same biosynthetic pathway as the target enzyme. Since the study of antifungal drug resistance is relatively new, other factors that may also contribute to resistance are discussed.

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Hidden Killers: Human Fungal Infections

2012-12-19

Gordon D. Brown , David W. Denning , Neil A. R. Gow +3 more

The lack of robust rapid diagnostic tests, safe and effective drugs, and preventative vaccines hampers treatment of patients with invasive fungal infections. The lack of robust rapid diagnostic tests, safe and effective drugs, and preventative vaccines hampers treatment of patients with invasive fungal infections.

Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant‐Associated Infection Surveillance Network (TRANSNET) Database

2010-03-10

Dimitrios P. Kontoyiannis , Kieren A. Marr , Benjamin J. Park +7 more

The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies.The Transplant Associated … The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies.The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts.We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT.In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.

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Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

2012-11-23

Janaína de Cássia Orlandi Sardi , Liliana Scorzoni , Thais Bernardi +2 more

The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, … The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, which retain many side effects. Candida species are major human fungal pathogens that cause both mucosal and deep tissue infections. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth. Biofilms are biological communities with a high degree of organization, in which micro-organisms form structured, coordinated and functional communities. These biological communities are embedded in a self-created extracellular matrix. Biofilm production is also associated with a high level of antimicrobial resistance of the associated organisms. The ability of Candida species to form drug-resistant biofilms is an important factor in their contribution to human disease. The study of plants as an alternative to other forms of drug discovery has attracted great attention because, according to the World Health Organization, these would be the best sources for obtaining a wide variety of drugs and could benefit a large population. Furthermore, silver nanoparticles, antibodies and photodynamic inactivation have also been used with good results. This article presents a brief review of the literature regarding the epidemiology of Candida species, as well as their pathogenicity and ability to form biofilms, the antifungal activity of natural products and other therapeutic options.

Secular Trends in the Epidemiology of Nosocomial Fungal Infections in the United States, 1980-1990

1993-05-01

C. M. B. Sague , William R. Jarvis

To identify pathogens causing nosocomial fungal infections and the secular trend in their incidence in US hospitals, data from the National Nosocomial Infections Surveillance System, 1980-1990, were analyzed. During that … To identify pathogens causing nosocomial fungal infections and the secular trend in their incidence in US hospitals, data from the National Nosocomial Infections Surveillance System, 1980-1990, were analyzed. During that period, 30,477 fungal infections were reported. The rate rose from 2.0 to 3.8 infections/1000 discharges. The highest number of nosocomial fungal infections/1000 discharges was reported from the burn/trauma service (16.1). Candida albicans was the most frequently isolated fungal pathogen (59.7%), followed by other Candida species (18.6%). The rate increased at all four major anatomic sites of infection. Patients with bloodstream infections who had a central intravascular catheter were more likely to have a fungal pathogen isolated than were other patients with bloodstream infection (relative risk = 3.2; P < .001): 29% of fungemia patients and 17% of patients with bloodstream infection due to other pathogens died during hospitalization (P < .001). Fungi are emerging as important nosocomial pathogens and control efforts should target fungal infections, especially fungemia.

Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America

2008-01-04

Thomas J. Walsh , Elias Anaissie , David W. Denning +7 more

Aspergillus species have emerged as an important cause of life-threatening infections in immunocompromised patients. This expanding population is composed of patients with prolonged neutropenia, advanced HIV infection, and inherited immunodeficiency … Aspergillus species have emerged as an important cause of life-threatening infections in immunocompromised patients. This expanding population is composed of patients with prolonged neutropenia, advanced HIV infection, and inherited immunodeficiency and patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) and/or lung transplantation. This document constitutes the guidelines of the Infectious Diseases Society of America for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2000 [1]. The objective of these guidelines is to summarize the current evidence for treatment of different forms of aspergillosis. The quality of evidence for treatment is scored according to a standard system used in other Infectious Diseases Society of America guidelines. This document reviews guidelines for management of the 3 major forms of aspergillosis: invasive aspergillosis, chronic (and saprophytic) forms of aspergillosis, and allergic forms of aspergillosis. Given the public health importance of invasive aspergillosis, emphasis is placed on the diagnosis, treatment, and prevention of the different forms of invasive aspergillosis, including invasive pulmonary aspergillosis, sinus aspergillosis, disseminated aspergillosis, and several types of single-organ invasive aspergillosis. There are few randomized trials on the treatment of invasive aspergillosis. The largest randomized controlled trial demonstrates that voriconazole is superior to deoxycholate amphotericin B (D-AMB) as primary treatment for invasive aspergillosis. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients (A-I). Although invasive pulmonary aspergillosis accounts for the preponderance of cases treated with voriconazole, voriconazole has been used in enough cases of extrapulmonary and disseminated infection to allow one to infer that voriconazole is effective in these cases. A randomized trial comparing 2 doses of liposomal amphotericin B (L-AMB) showed similar efficacy in both arms, suggesting that liposomal therapy could be considered as alternative primary therapy in some patients (A-I). For salvage therapy, agents include lipid formulations of amphotericin (LFAB; A-II), posaconazole (B-II), itraconazole (B-II), caspofungin (B-II), or micafungin (B-II). Salvage therapy for invasive aspergillosis poses important challenges with significant gaps in knowledge. In patients whose aspergillosis is refractory to voriconazole, a paucity of data exist to guide management. Therapeutic options include a change of class using an amphotericin B (AMB) formulation or an echinocandin, such as caspofungin (B-II); further use of azoles should take into account host factors and pharmacokinetic considerations. Refractory infection may respond to a change to another drug class (B-II) or to a combination of agents (B-II). The role of combination therapy in the treatment of invasive aspergillosis as primary or salvage therapy is uncertain and warrants a prospective, controlled clinical trial. Assessment of patients with refractory aspergillosis may be difficult. In evaluating such patients, the diagnosis of invasive aspergillosis should be established if it was previously uncertain and should be confirmed if it was previously known. The drug dosage should be considered. Management options include a change to intravenous (IV) therapy, therapeutic monitoring of drug levels, change of drug class, and/or combination therapy. Antifungal prophylaxis with posaconazole can be recommended in the subgroup of HSCT recipients with graft-versus-host disease (GVHD) who are at high risk for invasive aspergillosis and in neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome who are at high risk for invasive aspergillosis (A-I). Management of breakthrough invasive aspergillosis in the context of mould-active azole prophylaxis is not defined by clinical trial data. The approach to such patients should be individualized on the basis of clinical criteria, including host immunosuppression, underlying disease, and site of infection, as well as consideration of antifungal dosing, therapeutic monitoring of drug levels, a switch to IV therapy, and/or a switch to another drug class (B-III). Certain conditions of invasive aspergillosis warrant consideration for surgical resection of the infected focus. These include but are not limited to pulmonary lesions contiguous with the heart or great vessels, invasion of the chest wall, osteomyelitis, pericardial infection, and endocarditis (B-III). Restoration of impaired host defenses is critical for improved outcome of invasive aspergillosis (A-III). Recovery from neutropenia in a persistently neutropenic host or reduction of corticosteroids in a patient receiving high-dose glucocorticosteroids is paramount for improved outcome in invasive aspergillosis. A special consideration is made concerning recommendations for therapy of aspergillosis in uncommon sites, such as osteomyelitis and endocarditis. There are very limited data on these infections, and most involve D-AMB as primary therapy simply because of its long-standing availability. Based on the strength of the randomized study, the panel recommends voriconazole for primary treatment of these very uncommon manifestations of invasive aspergillosis (B-III). Management of the chronic or saprophytic forms of aspergillosis varies depending on the condition. Single pulmonary aspergillomas may be best managed by surgical resection (B-III), whereas chronic cavitary and chronic necrotizing pulmonary aspergillosis require long-term medical therapy (B-III). The management of allergic forms of aspergillosis involves a combination of medical and anti-inflammatory therapy. For example, management of allergic bronchopulmonary aspergillosis (ABPA) involves the administration of itraconazole and corticosteroids (A-I). © 2008 by the Infectious Diseases Society of America. All rights reserved.

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Biofilm Formation by the Fungal Pathogen Candida albicans : Development, Architecture, and Drug Resistance

2001-09-15

Jyotsna Chandra , Duncan M. Kuhn , Pranab K. Mukherjee +3 more

ABSTRACT Biofilms are a protected niche for microorganisms, where they are safe from antibiotic treatment and can create a source of persistent infection. Using two clinically relevant Candida albicans biofilm … ABSTRACT Biofilms are a protected niche for microorganisms, where they are safe from antibiotic treatment and can create a source of persistent infection. Using two clinically relevant Candida albicans biofilm models formed on bioprosthetic materials, we demonstrated that biofilm formation proceeds through three distinct developmental phases. These growth phases transform adherent blastospores to well-defined cellular communities encased in a polysaccharide matrix. Fluorescence and confocal scanning laser microscopy revealed that C. albicans biofilms have a highly heterogeneous architecture composed of cellular and noncellular elements. In both models, antifungal resistance of biofilm-grown cells increased in conjunction with biofilm formation. The expression of agglutinin-like ( ALS ) genes, which encode a family of proteins implicated in adhesion to host surfaces, was differentially regulated between planktonic and biofilm-grown cells. The ability of C. albicans to form biofilms contrasts sharply with that of Saccharomyces cerevisiae , which adhered to bioprosthetic surfaces but failed to form a mature biofilm. The studies described here form the basis for investigations into the molecular mechanisms of Candida biofilm biology and antifungal resistance and provide the means to design novel therapies for biofilm-based infections.

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Dectin-1 Mediates the Biological Effects of β-Glucans

2003-04-28

Gordon D. Brown , Jürgen Herre , David L. Williams +3 more

The ability of fungal-derived β-glucan particles to induce leukocyte activation and the production of inflammatory mediators, such as tumor necrosis factor (TNF)-α, is a well characterized phenomenon. Although efforts have … The ability of fungal-derived β-glucan particles to induce leukocyte activation and the production of inflammatory mediators, such as tumor necrosis factor (TNF)-α, is a well characterized phenomenon. Although efforts have been made to understand how these carbohydrate polymers exert their immunomodulatory effects, the receptors involved in generating these responses are unknown. Here we show that Dectin-1 mediates the production of TNF-α in response to zymosan and live fungal pathogens, an activity that occurs at the cell surface and requires the cytoplasmic tail and immunoreceptor tyrosine activation motif of Dectin-1 as well as Toll-like receptor (TLR)-2 and Myd88. This is the first demonstration that the inflammatory response to pathogens requires recognition by a specific receptor in addition to the TLRs. Furthermore, these studies implicate Dectin-1 in the production of TNF-α in response to fungi, a critical step required for the successful control of these pathogens.

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Defining Opportunistic Invasive Fungal Infections in Immunocompromised Patients with Cancer and Hematopoietic Stem Cell Transplants: An International Consensus

2002-01-01

Sibel Aşçıoğlu , John Rex , Ben de Pauw +7 more

During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal … During the past several decades, there has been a steady increase in the frequency of opportunistic invasive fungal infections (IFIs) in immunocompromised patients. However, there is substantial controversy concerning optimal diagnostic criteria for these IFIs. Therefore, members of the 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 formed a consensus committee to develop standard definitions for IFIs for clinical research. On the basis of a review of literature and an international consensus, a set of research-oriented definitions for the IFIs most often seen and studied in immunocompromised patients with cancer is proposed. Three levels of probability are proposed: "proven," "probable," and "possible." The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making.

Candida albicansSecreted Aspartyl Proteinases in Virulence and Pathogenesis

2003-09-01

Julian R. Naglik , Stephen Challacombe , Bernhard Hube

Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under … Candida albicans is the most common fungal pathogen of humans and has developed an extensive repertoire of putative virulence mechanisms that allows successful colonization and infection of the host under suitable predisposing conditions. Extracellular proteolytic activity plays a central role in Candida pathogenicity and is produced by a family of 10 secreted aspartyl proteinases (Sap proteins). Although the consequences of proteinase secretion during human infections is not precisely known, in vitro, animal, and human studies have implicated the proteinases in C. albicans virulence in one of the following seven ways: (i) correlation between Sap production in vitro and Candida virulence, (ii) degradation of human proteins and structural analysis in determining Sap substrate specificity, (iii) association of Sap production with other virulence processes of C. albicans, (iv) Sap protein production and Sap immune responses in animal and human infections, (v) SAP gene expression during Candida infections, (vi) modulation of C. albicans virulence by aspartyl proteinase inhibitors, and (vii) the use of SAP-disrupted mutants to analyze C. albicans virulence. Sap proteins fulfill a number of specialized functions during the infective process, which include the simple role of digesting molecules for nutrient acquisition, digesting or distorting host cell membranes to facilitate adhesion and tissue invasion, and digesting cells and molecules of the host immune system to avoid or resist antimicrobial attack by the host. We have critically discussed the data relevant to each of these seven criteria, with specific emphasis on how this proteinase family could contribute to Candida virulence and pathogenesis.

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Epidemiology and Clinical Manifestations of Mucormycosis

2012-01-13

G. Petrikkos , Anna Skiada , Olivier Lortholary +3 more

Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. Mucormycosis has emerged as the third most common invasive … Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Mucorales order of the class of Zygomycetes. Mucormycosis has emerged as the third most common invasive mycosis in order of importance after candidiasis and aspergillosis in patients with hematological and allogeneic stem cell transplantation. Mucormycosis also remains a threat in patients with diabetes mellitus in the Western world. Furthermore, this disease is increasingly recognized in recently developed countries, such as India, mainly in patients with uncontrolled diabetes or trauma. Epidemiological data on this type of mycosis are scant. Therefore, our ability to determine the burden of disease is limited. Based on anatomic localization, mucormycosis can be classified as one of 6 forms: (1) rhinocerebral, (2) pulmonary, (3) cutaneous, (4) gastrointestinal, (5) disseminated, and (6) uncommon presentations. The underlying conditions can influence clinical presentation and outcome. This review describes the emerging epidemiology and the clinical manifestations of mucormycosis.

Isogenic strain construction and gene mapping in Candida albicans.

1993-07-01

William A. Fonzi , M Y Irwin

Genetic manipulation of Candida albicans is constrained by its diploid genome and asexual life cycle. Recessive mutations are not expressed when heterozygous and undesired mutations introduced in the course of … Genetic manipulation of Candida albicans is constrained by its diploid genome and asexual life cycle. Recessive mutations are not expressed when heterozygous and undesired mutations introduced in the course of random mutagenesis cannot be removed by genetic back-crossing. To circumvent these problems, we developed a genotypic screen that permitted identification of a heterozygous recessive mutation at the URA3 locus. The mutation was introduced by targeted mutagenesis, homologous integration of transforming DNA, to avoid introduction of extraneous mutations. The ura3 mutation was rendered homozygous by a second round of transformation resulting in a Ura- strain otherwise isogenic with the parental clinical isolate. Subsequent mutation of the Ura- strain was achieved by targeted mutagenesis using the URA3 gene as a selectable marker. URA3 selection was used repeatedly for the sequential introduction of mutations by flanking the URA3 gene with direct repeats of the Salmonella typhimurium hisG gene. Spontaneous intrachromosomal recombination between the flanking repeats excised the URA3 gene restoring a Ura- phenotype. These Ura- segregants were selected on 5-fluoroorotic acid-containing medium and used in the next round of mutagenesis. To permit the physical mapping of disrupted genes, the 18-bp recognition sequence of the endonuclease I-SceI was incorporated into the hisG repeats. Site-specific cleavage of the chromosome with I-SceI revealed the position of the integrated sequences.

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Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

2007-01-01

Michael A. Pfaller , Daniel J. Diekema

SUMMARY Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in … SUMMARY Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.

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Candida albicanspathogenicity mechanisms

2013-02-07

François L. Mayer , Duncan Wilson , Bernhard Hube

The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans … The polymorphic fungus Candida albicans is a member of the normal human microbiome. In most individuals, C. albicans resides as a lifelong, harmless commensal. Under certain circumstances, however, C. albicans can cause infections that range from superficial infections of the skin to life-threatening systemic infections. Several factors and activities have been identified which contribute to the pathogenic potential of this fungus. Among them are molecules which mediate adhesion to and invasion into host cells, the secretion of hydrolases, the yeast-to-hypha transition, contact sensing and thigmotropism, biofilm formation, phenotypic switching and a range of fitness attributes. Our understanding of when and how these mechanisms and factors contribute to infection has significantly increased during the last years. In addition, novel virulence mechanisms have recently been discovered. In this review we present an update on our current understanding of the pathogenicity mechanisms of this important human pathogen.

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Antifungal Agents: Mode of Action, Mechanisms of Resistance, and Correlation of These Mechanisms with Bacterial Resistance

1999-10-01

Mahmoud A. Ghannoum , Louis B. Rice

The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to … The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. In this review, the mode of action of antifungals and their mechanisms of resistance are discussed. Additionally, an attempt is made to discuss the correlation between fungal and bacterial resistance. Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors defined in the review, a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.

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Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant‐Associated Infection Surveillance Network (TRANSNET)

2010-03-10

Peter G. Pappas , Barbara D. Alexander , David R. Andes +7 more

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking.The Transplant-Associated … Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking.The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts.During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005.We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.

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Epidemiology and Outcome of Zygomycosis: A Review of 929 Reported Cases

2005-08-05

Maureen Roden , Theoklis E. Zaoutis , Wendy Buchanan +7 more

Background. Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. Methods. We reviewed reports of zygomycosis … Background. Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. Methods. We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. Results. The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 [60%] of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 [66%] of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 [33%] of 337), compared with patients with malignancy (6 [4%] of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). Conclusions. Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.

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Clinical Practice Guidelines for the Management Candidiasis: 2009 Update by the Infectious Diseases Society of America

2009-01-29

Peter G. Pappas , Carol A. Kauffman , David R. Andes +7 more

Abstract Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace … Abstract Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

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Aspergillus fumigatusand Aspergillosis

1999-04-01

Jean‐Paul Latgé

SUMMARY Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in … SUMMARY Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.

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Current and Emerging Azole Antifungal Agents

1999-01-01

Daniel J. Sheehan , Christopher A. Hitchcock , Carol M. Sibley

SUMMARY Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole … SUMMARY Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging. This review describes present and future uses of the currently available azole antifungal agents in the treatment of systemic and superficial fungal infections and provides a brief overview of the current status of in vitro susceptibility testing and the growing problem of clinical resistance to the azoles. Use of the currently available azoles in combination with other antifungal agents with different mechanisms of action is likely to provide enhanced efficacy. Detailed information on some of the second-generation triazoles being developed to provide extended coverage of opportunistic, endemic, and emerging fungal pathogens, as well as those in which resistance to older agents is becoming problematic, is provided.

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Novel Perspectives on Mucormycosis: Pathophysiology, Presentation, and Management

2005-07-01

Brad Spellberg , John E. Edwards , Ashraf S. Ibrahim

SUMMARY Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of … SUMMARY Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement.

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Candida biofilms and their role in infection

2003-01-01

Laura Douglas

ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients

2012-09-25

Oliver A. Cornely , Matteo Bassetti , Thierry Calandra +7 more

Time to Initiation of Fluconazole Therapy Impacts Mortality in Patients with Candidemia: A Multi‐Institutional Study

2006-06-07

Kevin W. Garey , M Rege , Manjunath P. Pai +4 more

Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of … Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality.We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast.A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05).A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.

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Revised Definitions of Invasive Fungal Disease from the 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 (EORTC/MSG) Consensus Group

2008-05-07

Ben de Pauw , Thomas J. Walsh , J. Peter Donnelly +7 more

Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set … Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies.After the introduction of the original 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 (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved.The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only.These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

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Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America

2015-12-16

Peter G. Pappas , Carol A. Kauffman , David R. Andes +7 more

Abstract It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or … Abstract It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

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Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America

2016-01-22

Peter G. Pappas , Carol A. Kauffman , David R. Andes +7 more

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A Controlled Trial of Fluconazole to Prevent Fungal Infections in Patients Undergoing Bone Marrow Transplantation

1992-03-26

Jesse L. Goodman , Drew J. Winston , Ronald A. Greenfield +7 more

Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a doubleblind, randomized, multicenter trial in which patients receiving bone … Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a doubleblind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved.

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J Antimicrob Chemother 1994; 33: 350–351

1994-01-01

Elizabeth O’Shaughnessy , Satya Das

Journal Article J Antimicrob Chemother 1994; 33: 350–351 Get access ELIZABETH M. O'SHAUGHNESSY, ELIZABETH M. O'SHAUGHNESSY Department of Medical Microbiology, St Bartholomew's Hospital Medical CollegeWest Smithfield, London EC1A 7BE, UK … Journal Article J Antimicrob Chemother 1994; 33: 350–351 Get access ELIZABETH M. O'SHAUGHNESSY, ELIZABETH M. O'SHAUGHNESSY Department of Medical Microbiology, St Bartholomew's Hospital Medical CollegeWest Smithfield, London EC1A 7BE, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar SATYA S. DAS SATYA S. DAS Department of Medical Microbiology, St Bartholomew's Hospital Medical CollegeWest Smithfield, London EC1A 7BE, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 33, Issue 2, February 1994, Pages 350–351, https://doi.org/10.1093/jac/33.2.350 Published: 01 February 1994

Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America

2016-06-29

Thomas F. Patterson , George R. Thompson , David W. Denning +7 more

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special … It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

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Simultaneous Emergence of Multidrug-ResistantCandida aurison 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses

2016-10-15

Shawn R. Lockhart , Kizee A. Etienne , Snigdha Vallabhaneni +7 more

Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. To understand the global emergence and … Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

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Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision

2017-10-18

Felix Bongomin , Sara Gago , Rita Oladele +1 more

Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal … Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.

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Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline

2018-03-18

Andrew J. Ullmann , José María Aguado , Sevtap Arıkan-Akdağlı +7 more

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Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

2019-11-05

Oliver A. Cornely , Ana Alastruey‐Izquierdo , Dorothee Arenz +7 more

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Invasive candidiasis

2018-05-10

Peter G. Pappas , Michail S. Lionakis , Maiken Cavling Arendrup +2 more

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Invasive Aspergillosis

1998-04-01

David W. Denning

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Invasive pulmonary aspergillosis in an immunocompetent adult: A case report

2025-06-25

Manouri Gamage , Janaka Kalubowila , Suresh Mendis +4 more | Sri Lankan Journal of Infectious Diseases

Invasive pulmonary aspergillosis is a severe potentially life-threatening infection, usually affecting immunocompromised patients and caused by many species of Aspergillus. It is usually diagnosed based on a combination of clinical, … Invasive pulmonary aspergillosis is a severe potentially life-threatening infection, usually affecting immunocompromised patients and caused by many species of Aspergillus. It is usually diagnosed based on a combination of clinical, microbiological and radiological findings. Since it is rarely reported in immunocompetent people, diagnosis can be delayed. We report a case of invasive pulmonary aspergillosis in a male patient who presented with features of community acquired pneumonia. The importance of radiological features and serological tests and timely institution of appropriate treatment, monitoring and assessing clinical response has been emphasised.

Development and validation of an RP-HPLC method for the quantitative estimation of itraconazole in bulk and capsule dosage forms

2025-06-24

M. Sunitha Reddy , M. Murali Krishna Kumar M.Srinu , M. RAJITHA +3 more | International Journal of Science and Research Archive

This study presents the development and validation of a simple, precise, accurate, and robust Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the quantitative analysis of Itraconazole in bulk and … This study presents the development and validation of a simple, precise, accurate, and robust Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the quantitative analysis of Itraconazole in bulk and capsule forms. Chromatographic separation was carried out using a C18 column with an optimized mobile phase, flow rate, and detection wavelength to ensure effective resolution and symmetrical peak shapes. The method was validated in accordance with ICH guidelines, assessing parameters such as linearity, precision, accuracy, specificity, robustness, limit of detection (LOD), and limit of quantification (LOQ). The developed method demonstrated excellent linearity (R² > 0.999), accuracy with recoveries between 98–102%, and precision with RSD below 2%. No interference was observed from excipients or degradation products, confirming the method’s specificity. Robustness testing confirmed the system’s reliability under minor changes in conditions. Therefore, this RP-HPLC method is suitable for routine quality control of Itraconazole in pharmaceutical formulations

Identification and Antifungal Susceptibility of Candida Species in Canine Oral Flora

2025-06-24

Oğuzhan Dolgun , Hafize Tuğba Yüksel Dolgun , Yiğit Seferoğlu +1 more | Animal Health Production and Hygiene

In this study, the presence of Candida species was investigated in 60 oral swab samples collected from dogs. The samples were cultured on Candida chromogenic agar and incubated at 30°C … In this study, the presence of Candida species was investigated in 60 oral swab samples collected from dogs. The samples were cultured on Candida chromogenic agar and incubated at 30°C for 48 hours. Following the incubation period, growth was observed on 30 (50%) of the plates, resulting in the isolation of 57 Candida colonies. These colonies exhibited growth either as single or multiple agents on the chromogenic agar. Species identification was performed based on the color patterns displayed on the chromogenic agar, leading to the detection of six distinct Candida species. Among the isolates, 16 (28.1%) were identified as Candida krusei, 10 (17.5%) as Candida glabrata, 10 (17.5%) as Candida parapsilosis, 9 (15.8%) as Candida utilis, 7 (12.3%) as Candida tropicalis, and 5 (8.8%) as Candida albicans. To confirm their identification at the molecular level, all isolates were verified as belonging to the Candida genus using PCR with ITS3-ITS4 primers. The antifungal susceptibility of the isolates (n=57) was assessed using the disk diffusion method. The results revealed that the isolates exhibited resistance to miconazole (43.8%), ketoconazole (26.3%), flucytosine (100%), and fluconazole (93.1%), while showing high sensitivity to nystatin (93.1%). This study highlights the presence of pathogenic Candida species in the oral flora of dogs and underscores the emergence of antifungal resistance among these isolates. The findings suggest that the presence of Candida species in the oral microbiota of dogs could pose a potential health risk to both animals and humans, particularly in immunocompromised individuals.

Diagnostic Approaches for Candida auris: A Comprehensive Review of Screening, Identification, and Susceptibility Testing

2025-06-24

C.-L. Hsu , Mohamed Yassin | Microorganisms

Candida auris (C. auris) is an emerging multidrug-resistant fungal pathogen recognized by the World Health Organization (WHO) as a critical global health threat. Its rapid transmission, high mortality rate, and … Candida auris (C. auris) is an emerging multidrug-resistant fungal pathogen recognized by the World Health Organization (WHO) as a critical global health threat. Its rapid transmission, high mortality rate, and frequent misidentification in clinical laboratories present significant challenges for diagnosis and infection control. This review provides a comprehensive overview of current and emerging diagnostic methods for C. auris detection, including culture-based techniques, biochemical assays, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and molecular diagnostics such as PCR and loop-mediated isothermal amplification (LAMP). We evaluate each method’s sensitivity, specificity, turnaround time, and feasibility in clinical and surveillance settings. While culture remains the diagnostic gold standard, it is limited by slow turnaround and phenotypic overlap with related species. Updated biochemical platforms and MALDI-TOF MS with expanded databases have improved identification accuracy. Molecular assays offer rapid, culture-independent detection. Antifungal susceptibility testing (AFST), primarily using broth microdilution, is essential for guiding treatment, although standardized breakpoints remain lacking. This review proposes an integrated diagnostic workflow and discusses key innovations and gaps in current practice. Our findings aim to support clinicians, microbiologists, and public health professionals in improving early detection, containment, and management of C. auris infections.

Pathogenicity Evaluation on Fluconazole-Resistant Candida auris Clade V in Murine Model

2025-06-24

Robab Ebrahimi Barough , Hamid Badali , Fereshteh Talebpour Amiri +7 more | Mycopathologia

Early Outcomes of PSI-Integrated Abutments for Functional Restoration in Post-COVID-19 Mucormycosis

2025-06-24

Sharath K Rao , Arjun K. Ghosh | International Journal of Oral and Maxillofacial Surgery

Emergence of Flucytosine-Resistant Candida tropicalis Clade, the Netherlands

2025-06-24

Fatima Zohra Delma , Bram Spruijtenburg , Jacques F. Meis +7 more | Emerging infectious diseases

Candida tropicalis is the second most virulent Candida species after C. albicans. Previous studies from the Netherlands and France reported a notable reduction in susceptibility to flucytosine (5-FC) in a … Candida tropicalis is the second most virulent Candida species after C. albicans. Previous studies from the Netherlands and France reported a notable reduction in susceptibility to flucytosine (5-FC) in a substantial proportion of C. tropicalis isolates. We investigated epidemiologic patterns of C. tropicalis isolates in the Netherlands and the genetic mechanisms driving widespread non-wild-type (WT) 5-FC resistance. We conducted antifungal susceptibility testing and used advanced molecular techniques, including short tandem repeat genotyping and whole-genome sequencing paired with single-nucleotide polymorphism analysis, to analyze 250 C. tropicalis isolates collected across the Netherlands during 2012-2022. Our findings revealed the rapid emergence of a 5-FC-resistant, non-WT C. tropicalis clade, accounting for >40% of all C. tropicalis isolates by 2022. Genomic analysis identified a homozygous nonsense mutation in the FCY2 gene, which was exclusive to this non-WT population. Continued surveillance efforts are needed to detect and prevent the spread of drug-resistant Candida species.

Successful Medical Management of Gastrointestinal Invasive Mucormycosis with Associated Bowel Perforation in an Adolescent Patient with pre‐B Cell Acute Lymphoblastic Leukemia

2025-06-23

Heather Valdin , Kathleen Condon , M Dietrich +4 more | Pediatric Blood & Cancer

Host targets of candidalysin

2025-06-23

Jianfeng Lin , Scott G. Filler | PLoS Pathogens

Candida albicans is a normal constituent of the human microbiota and a ubiquitous human threat. This fungus causes diseases ranging from superficial cutaneous and mucosal candidiasis to life-threatening disseminated candidiasis. … Candida albicans is a normal constituent of the human microbiota and a ubiquitous human threat. This fungus causes diseases ranging from superficial cutaneous and mucosal candidiasis to life-threatening disseminated candidiasis. C. albicans hyphae secrete candidalysin, a cytolytic peptide toxin that damages host cells and activates immune responses. Candidalysin plays a key role in both pathogenicity and commensalism. In this Pearl, we review the host targets of candidalysin and how they modulate the interaction of C. albicans with the host.

Heterogeneity of Candida bloodstream isolates in an academic medical center and affiliated hospitals

2025-06-23

Nancy E. Scott , Elizabeth Wash , Christopher Zajac +3 more | Microbiology Spectrum

Invasive Candida bloodstream infections (candidemia) are a deadly global health threat. Rare Candida species are becoming increasingly important causes of candidemia. Phenotypic data, including patterns of antifungal drug resistance, are … Invasive Candida bloodstream infections (candidemia) are a deadly global health threat. Rare Candida species are becoming increasingly important causes of candidemia. Phenotypic data, including patterns of antifungal drug resistance, are limited. There is a geographic variation in the distribution of Candida species and frequency of antifungal drug resistance, meaning that regional data can have significant clinical value. Here, we report on the species distribution, frequency of antifungal drug resistance, and phenotypic variability of Candida bloodstream isolates from an academic medical center and five affiliated hospitals in the Minneapolis-Saint Paul region of Minnesota collected during an 18-month period from 2019 to 2021. We collected 288 isolates spanning 11 species from 119 patients. C. albicans was recovered from 45% of cases, followed by C. glabrata (35%), C. parapsilosis (7%), and C. tropicalis (2.5%), with 10% of cases representing additional rare species. We performed antifungal drug susceptibility by the EUCAST (European Committee on Antimicrobial Susceptibility Testing) method for three major drug classes. Concerningly, we identified fluconazole, micafungin, and multidrug resistance rates in C. glabrata that were ~2 times higher than that reported in other regions of the United States. Through analysis of serial isolates from individual patients, we identified clinically relevant within-patient differences of MIC values in multiple drug classes. We also report phenotypic data in rare non-albicans Candida species to address a significant gap in available data. Our results provide valuable clinical data relevant to antifungal stewardship efforts and highlight important areas of future research, including within-patient dynamics of infection and the mechanisms of drug resistance in rare Candida species.IMPORTANCECandida species are an important cause of hospital-acquired infection. The prevalence of species causing infections and the frequency of antifungal drug resistance have changed over time. Reporting the regional Candida species distribution and phenotypes has clinical significance. Current clinical microbiology practices may underestimate the within-host diversity of infecting strains, including important variation in drug susceptibility. Our study reports the results of an 18-month survey of Candida bloodstream infections in an academic medical center and associated hospitals in the Minneapolis-Saint Paul region of Minnesota. We identified antifungal drug resistance, including multidrug resistance, in multiple non-albicans species. By analyzing serial isolates from individual patients, we identified clinically relevant differences in drug susceptibility during infection. Our results contribute data to antifungal stewardship efforts and identify avenues of future research.

Candida auris outbreak in a cardiothoracic transplant intensive care unit: implications for infection prevention practices and keeping pace with an evolving landscape

2025-06-23

Shardul N Rathod , Grace Barajas , Brooks I. Mitchell +7 more | Infection Control and Hospital Epidemiology

To describe the mitigation strategies for a Candida auris outbreak in a cardiothoracic transplant intensive care unit (CTICU) and its implications for infection prevention practices. Retrospective cohort study from July … To describe the mitigation strategies for a Candida auris outbreak in a cardiothoracic transplant intensive care unit (CTICU) and its implications for infection prevention practices. Retrospective cohort study from July 2023 to February 2024. A large academic medical center. A multidisciplinary team convened to conduct the outbreak investigation and develop mitigation strategies in the CTICU. From July 2023 to February 2024, 34 possible hospital-onset cases of C. auris were identified in our CTICU. Whole-genome sequencing and phylogenetic analysis based on pairwise single nucleotide polymorphism (WG-SNP) distance revealed two distinct outbreak clusters. Of the 34 patients, 11 (32.3%) were solid organ transplant recipients and 12 (35.3%) had a mechanical circulatory support device. Of the cohort, only 11/34 (32.3%) had prior exposure to high-risk healthcare facilities within six months prior to admission, as follows: acute inpatient rehabilitation facilities (AIRs) (n = 5, 14.7%), skilled nursing facilities (SNFs) (n = 3, 8.8%), and long-term acute care hospitals (LTACHs) (n = 3, 8.8%). The cohort had a median of 22.0 antibiotic-days prior to their positive results. Five (14.7%) patients had C. auris candidemia, three of whom expired likely due to infection. Infection Prevention (IP) interventions addressed several modes of transmission, including healthcare personnel hands, shared patient equipment, and the environment. Our experience suggests that the epidemiology of C. auris may be changing, pointing towards a rising prevalence in acute care settings. IP interventions targeting hand hygiene behavior and promoting centralizing cleaning and disinfection of shared patient equipment may have contributed to outbreak resolution.

New Generation Modified Azole Antifungals against Multidrug-Resistant Candida auris

2025-06-23

Yiyuan Chen , Yunxiao Li , Kazi S. Nahar +7 more | Journal of Medicinal Chemistry

The rise of antifungal resistance and limited treatment options highlight the urgent need for new drug classes. Candida auris is a serious global health threat with few effective therapies. In … The rise of antifungal resistance and limited treatment options highlight the urgent need for new drug classes. Candida auris is a serious global health threat with few effective therapies. In this study, novel azole-based compounds were developed by modifying the azole core with cyclic heteroaliphatic linkers connecting aromatic and heteroaromatic rings. Several compounds showed potent activity against C. auris, including azole-resistant strains, with MICs ranging from 0.016 to 4 μg/mL. The compounds also demonstrated strong activity against C. albicans, Nakaseomyces glabratus, C. tropicalis, and C. parapsilosis, with MICs mostly below 1 μg/mL. Compounds 7, 18, and 21 were more potent than fluconazole. Compound 7 inhibited CYP51, eradicated C. auris biofilms, and showed better intracellular accumulation than fluconazole. In vivo studies in Galleria mellonella and Drosophila melanogaster confirmed efficacy at 5 mg/kg and no toxicity up to 50 mg/kg, supporting further development of this scaffold against multidrug-resistant C. auris infections.

Finding Acridone as Potent Antifungal Ligand Targeting Virulent Proteins of Fungal Pathogen Candida albicans

2025-06-22

Anubhuti Jha , Jyoti Sankar Prusty , Awanish Kumar | Multiscale Science and Engineering

Disseminated Penicillium labradoris (synonym: P. labradorum) in three dogs from Western Australia

2025-06-22

LJ Tong , John P.H. Th'ng , Nola V. Lester +6 more | Australian Veterinary Journal

Introduction This case series presents three new cases of disseminated Penicillium labradoris (syn. P. labradorum ) infection in unrelated dogs from Western Australia, illustrating varied clinical presentations and outcomes. P. … Introduction This case series presents three new cases of disseminated Penicillium labradoris (syn. P. labradorum ) infection in unrelated dogs from Western Australia, illustrating varied clinical presentations and outcomes. P. labradoris infections are rare in dogs, with only three prior cases reported worldwide. Typically considered low‐virulence mycotic pathogens, Penicillium species can occasionally cause severe disease in dogs likely affected by some genetically programmed immune defect. Case Histories Case one was a three‐year‐old Staffordshire bull terrier crossbreed who presented for lameness, metatarsal swelling and lymphadenomegaly. Radiographs showed osteomyelitis and P. labradoris was cultured from both bone and lymph node biopsy specimens. Treatment included en bloc metatarsal excision and long‐term antifungal therapy, initially with voriconazole and terbinafine, and subsequently delayed‐release posaconazole. Currently, 1217 days post‐diagnosis, the dog remains clinically well with only mild biomarker elevations. The second case featured bilateral asymmetrical forelimb fungal osteomyelitis with more severe left forelimb involvement and demonstrated a good clinical response to delayed‐release posaconazole and terbinafine. The third case presented with severe disseminated infection affecting multiple organ systems, including lymphadenomegaly, gastrointestinal and pulmonary involvement, and tri‐cavitary effusion. Despite treatment with posaconazole, terbinafine, and voriconazole, the dog succumbed. Discussion and Relevance to Australian Clinical Practice This series underscores the variability of P. labradoris presentations in dogs and highlights potential for successful long‐term management with posaconazole therapy. Serial biomarker determinations and therapeutic drug monitoring play a crucial role in guiding treatment. These cases suggest intriguing aspects of pathogen virulence and potential genetic susceptibility in individual unrelated dogs. Although this fungal species is present in the US, France, and Brazil, it is of great interest that all three Australian cases were from Perth, Western Australia.

Enhanced performances of the short-PCR coupled lateral flow assay in the detection of Candida albicans in clinical blood samples.

2025-06-22

Oranee Srichaiyapol , Bhanubong Saiboonjan , Sawinee Ngernpimai +7 more | PubMed

Candida albicans remains the most common fungal pathogen among the species, causing candidemia. Thus, early diagnosis is indispensable in patients with severe underlying infections. To develop a short-polymerase chain reaction … Candida albicans remains the most common fungal pathogen among the species, causing candidemia. Thus, early diagnosis is indispensable in patients with severe underlying infections. To develop a short-polymerase chain reaction (short-PCR) coupled with lateral flow strip (LFS) assay for the detection of C. albicans in clinical blood samples. A short-PCR-LFS was enhanced to detect clinical isolates and clinical blood samples. The ITS2 gene of C. albicans was amplified using the modified primers-probes to produce highly specific, dual-labeled amplicons. The sensitivity and specificity of the test system were evaluated using C. albicans, Candida spp. other than C. albicans and other microbial DNAs. The test system was validated by 44 clinical isolates and 51 clinical blood samples. The short-PCR-LFS revealed a high specificity for C. albicans with no cross-reactivity and a limit of detection (LOD) of 0.1 ng per 2 mL of blood and 2 CFU/mL using a direct colony as a template. The result was consistent with the validation by short-PCR agarose gel electrophoresis (AGE). The short-PCR-LFS assay showed all positives with all C. albicans relevant samples and exhibited negative for other microbial relevance samples. The entire process of this system provides visual detection results less than 1 h with high sensitivity, high specificity, DNA extraction-free method, and little dependence on instruments. Thus, it can be considered as a promising method for professional use to early detect and identify clinical relevance samples of C. albicans.

Pathogenic Features, Experimental Models, and Molecular Tools of Human Fungal Pathogens: Who’s on WHO’s Radar?

2025-06-22

Aswathy Narayanan , Amrutha Ambily Shaji , Dileep Pullepu +2 more | ACS Infectious Diseases

With the prevalence of immunocompromising infections, the emergence of new pathogenic species, rising multidrug resistance, hospital outbreaks, and high mortality rates, once neglected fungal pathogens are now taking over the … With the prevalence of immunocompromising infections, the emergence of new pathogenic species, rising multidrug resistance, hospital outbreaks, and high mortality rates, once neglected fungal pathogens are now taking over the global healthcare arena, necessitating breakthroughs in diagnostics and therapeutics. The World Health Organization (WHO) recently published a list of critical and high-priority fungal pathogens, underlining the need and significance of broadening the focus to include fungal infections, among other life-threatening infectious diseases. This is also a wake-up call to the scientific community to facilitate a better understanding of the emergence, life cycle, spread, virulence, and drug resistance mechanisms in fungal pathogens. The strategies that fungal pathogens adopt to escape the immune system, establish an infection, and combat antifungal drugs are diverse. In this review, we focus on the pathogenic lifestyles of WHO critical and high priority fungal pathogens, with a brief introduction to the epidemiology and infection statistics.

Danazol/ixekizumab/secukinumab

2025-06-21

| Reactions Weekly

Amphotericin-B-liposomal/voriconazole

2025-06-21

| Reactions Weekly

Fluconazole resistant pathogenic yeasts isolated from plastic debris on recreational public beaches in West and East Africa

2025-06-21

Ayorinde B. Akinbobola , Dativa J. Shilla , Daniel Abel Shilla +1 more | Biologia

Abstract Plastic pollution in the environment becomes rapidly colonised by microbial communities, which often contain human bacterial pathogens. However, there is a lack of information about the interaction of fungal … Abstract Plastic pollution in the environment becomes rapidly colonised by microbial communities, which often contain human bacterial pathogens. However, there is a lack of information about the interaction of fungal pathogens with plastic debris, particularly in marine environments. This study screened common plastic wastes collected from a range of recreational public and tourist beaches in Nigeria and Tanzania for colonisation by human pathogenic yeasts. Isolates were identified on selective media with confirmation by ITS sequencing. All beaches and all plastic polymer types were colonised by at least one species of human pathogenic yeast, with Candida tropicalis being the most frequently isolated species across both countries. Importantly, most of these pathogenic yeast isolates showed some level of resistance to fluconazole, which in Africa is the most commonly prescribed anti-fungal drug. Therefore, due to the high potential for human skin exposure at beach environments, plastic debris could pose a significant public health risk.

Consensus Criteria for Invasive Fungal Infections: A 22-Year Review of EORTC Definitions

2025-06-21

Giulianna Pereira Tizzot , Luis Carreño , Marcello Mihailenko Chaves Magri +4 more | Current Tropical Medicine Reports

Amphotericin-B/echinocandins/voriconazole

2025-06-21

| Reactions Weekly

Infliximab/Methylprednisolone/Pembrolizumab/Prednisone

2025-06-21

| Reactions Weekly

Proteinase and Phospholipase as Virulence Determinants of Candida Isolates from Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders

2025-06-20

S. Palanisamy , Krishnan Mahalakshmi , Sankar Leena Sankari | World Journal of Dentistry

Microbiota and cancer: Elucidating the role of Candida albicans in cancer progression

2025-06-20

Lei Wang , Hao-Ling Zhang , Hao-Long Zhang +3 more | World Journal of Clinical Oncology

Candida albicans (C. albicans) represents one of the most prevalent opportunistic fungal pathogens in cancer patients. Although the association between C. albicans and cancer has been recognized for decades, the … Candida albicans (C. albicans) represents one of the most prevalent opportunistic fungal pathogens in cancer patients. Although the association between C. albicans and cancer has been recognized for decades, the causal relationship, whether C. albicans infection is a consequence of cancer or a direct contributor to cancer development-remains a subject of intensive investigation. Recently, the complex interplay between microbes and cancer has garnered significant attention within the scientific community, with growing interest in elucidating the underlying molecular mechanisms. This review systematically examines the biological characteristics of C. albicans, its multifaceted interactions with the host, and its relationship with the intestinal microbiota. Additionally, it provides a comprehensive analysis of the association between C. albicans and the development of various malignancies, with particular emphasis on digestive tract cancers. The review also identifies critical knowledge gaps and apparent contradictions in existing research, highlighting potential avenues for breakthroughs that will advance the efficient and accurate screening, diagnosis, and treatment of cancer.

Correction to “Systemic Acetylome Analysis of Evolution in Fluconazole Resistance Candida auris”

2025-06-20

Xiaowei Zhou , Danrui Jing , Yuying Huang +5 more | Journal of Proteome Research

Virulence Factors and Molecular Identification of Candida Species Causing Candidemia in Honduras

2025-06-20

Jaime E. Villena , Bryan Ortíz , Roque Sampedro López +7 more | Journal of Fungi

Invasive fungal infections (IFIs), primarily caused by Candida species, represent a significant global public health concern due to their high mortality rates and growing antifungal resistance. In Honduras, data on … Invasive fungal infections (IFIs), primarily caused by Candida species, represent a significant global public health concern due to their high mortality rates and growing antifungal resistance. In Honduras, data on their epidemiology remains scarce. This study aimed to characterize Candida species associated with candidemia and assess key virulence factors. A total of 80 clinical isolates were collected from four hospitals in Honduras’s major cities, Tegucigalpa and San Pedro Sula. Identification was performed using both phenotypic and molecular methods. Hemolytic activity, phospholipase and protease production, and biofilm formation were evaluated. C. albicans and C. tropicalis were the most prevalent species (30% each), followed by C. parapsilosis (27.5%). Phenotypic methods misidentified 13.8% of the isolates. Most strains (96.3%) exhibited strong hemolytic activity. C. albicans showed the highest phospholipase activity, while C. tropicalis was the most robust film producer. These findings highlight an evolving epidemiological landscape characterized by an increasing prevalence of non-albicans Candida species, often less susceptible to antifungal agents, and diverse virulence profiles such as strong biofilm formation. This underscores the clinical need for accurate species-level identification through molecular diagnostics and ongoing surveillance to guide targeted antifungal therapy and enable early, locally adapted interventions.

Investigation of voriconazole heteroresistance in clinical isolates of Trichosporon asahii from a multicenter study in China

2025-06-20

C C Liu , Qiaoying Gao , Yingxing Li +7 more | Microbiology Spectrum

ABSTRACT Heteroresistance refers to the presence of subpopulations within seemingly homogeneous microbial cells that exhibit varying sensitivities to antifungal agents, potentially contributing to treatment failure. Our study investigated the heteroresistance … ABSTRACT Heteroresistance refers to the presence of subpopulations within seemingly homogeneous microbial cells that exhibit varying sensitivities to antifungal agents, potentially contributing to treatment failure. Our study investigated the heteroresistance levels of clinical isolates of Trichosporon asahii collected from a multicenter study in China. A total of 62 isolates from 31 research centers, representing five different genotypes, were analyzed. We assessed the minimal inhibitory concentrations (MICs) of voriconazole (VRC), the level of heteroresistance to voriconazole (LHV), the strains’ capacity for adaptation to high VRC concentrations (ADP), and the stability of the heteroresistance phenomenon. The isolates had low VRC MICs (average 0.038 µg/mL), with 95.2% (59/62) classified as wild type. Heteroresistance to VRC was observed in all isolates, with an average LHV (0.25–4 µg/mL) 23 times higher than the MICs (0.012–0.19 µg/mL). Additionally, 90.3% of strains tolerated VRC concentrations at least 16 times the MICs, with heteroresistant subpopulations appearing at frequencies ranging from 0.002% to 0.830%. Furthermore, the strains rapidly adapted to elevated drug concentrations following brief exposure to VRC, with 71.0% tolerating VRC at 8 µg/mL and an average ADP value 285 times the MICs. However, the strains gradually lost this resistance when serially passaged on drug-free SDA plates, with the time required for resistance loss varying among strains. Our study is the first to reveal the presence of heteroresistance in clinical Trichosporon asahii , adding to the body of research on fungal heteroresistance and posing challenges to the clinical interpretation of MIC values for guiding treatment. IMPORTANCE Trichosporon asahii has become an increasingly important fungal pathogen responsible for invasive infections in clinical settings. Due to its natural resistance to flucytosine and echinocandin classes, azole drugs, especially voriconazole, are the mainstay of treatment. The phenomenon of heteroresistance may be associated with treatment failure in fungal infections; however, this phenomenon remains unclear in T. asahii . Our study provides the first comprehensive characterization of voriconazole heteroresistance in T. asahii, significantly advancing our understanding of antifungal resistance dynamics in this emerging pathogen. Our findings also challenge the reliability of conventional minimal inhibitory concentration-based therapeutic guidance for T. asahii infections.

Clinical and Radiological Response to Antifungal Treatment in Aspergilloma

2025-06-20

Emine Afşin , Zeliha Coşgun , Furkan Küçük | Infectious Diseases in Clinical Practice

Introduction Aspergilloma can be found in all forms of chronic aspergillosis except for Aspergillus nodules. Whether antifungal treatment or surgery should be the first option remains unclear. Our study retrospectively … Introduction Aspergilloma can be found in all forms of chronic aspergillosis except for Aspergillus nodules. Whether antifungal treatment or surgery should be the first option remains unclear. Our study retrospectively evaluated patients diagnosed with aspergilloma to investigate their clinical and radiologic responses to antifungal treatment. Materials and Methods We evaluated the demographic, radiological, laboratory, and clinical data; comorbidities; treatment processes (including duration and complications); and clinical and radiological responses after voriconazole treatment in 12 patients diagnosed with aspergilloma between January 2021 and May 2024. Results Radiological response to antifungal treatment was 22.2%, whereas clinical response was 66.7%. Patients with a history of ankylosing spondylitis (AS), previous tuberculosis (TB), destructed parenchyma, bronchiectasis, and old cavities on computed tomography (CT) had a higher, though not statistically significant, clinical response rate to antifungal treatment. The presence of pleural effusion and short treatment duration were associated with a decreased clinical response to treatment ( P = 0.018, P = 0.025). Conclusion In aspergilloma, antifungal therapy may be considered primarily for patients with AS, a history of TB, destructed parenchyma on CT, bronchiectasis, previous cavities, and no pleural effusion. Optimal adherence to the treatment duration will improve the clinical response.

Therapeutic Isavuconazole Concentration in a Patient With Acute on Chronic Liver Failure on Continuous Kidney Replacement Therapy

2025-06-20

Christopher Bunk , Stephen Rappaport , Emma Chee-How +2 more | Infectious Diseases in Clinical Practice

Abstract Isavuconazonium sulfate (Cresemba) is a newer broad-spectrum antifungal in the triazole class used to treat invasive aspergillosis and mucormycosis. Patients with impaired liver function may significantly accumulate the drug … Abstract Isavuconazonium sulfate (Cresemba) is a newer broad-spectrum antifungal in the triazole class used to treat invasive aspergillosis and mucormycosis. Patients with impaired liver function may significantly accumulate the drug however, and whether dose adjustment is necessary in patients with hepatic impairment and specifically in the setting of critical illness is unknown. A 57-year-old critically ill female with pulmonary aspergillosis and high-grade acute on chronic liver failure was treated with standard dose isavuconazonium sulfate. When a trough concentration was evaluated it was on the high end of the recommended, though poorly validated, range. Before routine dose reduction is undertaken, we suggest that further studies should be done to assess the appropriate dosing regimen for patients with hepatic impairment and those with critical illness as unnecessarily decreasing the isavuconazonium dose can lead to underexposure and potential treatment failure. Therapeutic drug monitoring also presents an appealing option.

Fungi under fire: diagnostic capacities and antifungal availability in Peruvian healthcare facilities

2025-06-20

Julio Maquera-Afaray , Luis E. Cuéllar , Oliver A. Cornely +7 more | Microbiology Spectrum

ABSTRACT Invasive fungal infections (IFI) are a significant global health issue, affecting an estimated 7 million people annually, with around 3 million deaths. In Peru, IFIs are estimated to affect … ABSTRACT Invasive fungal infections (IFI) are a significant global health issue, affecting an estimated 7 million people annually, with around 3 million deaths. In Peru, IFIs are estimated to affect about 2% of the population. Underdiagnosis due to the limited sensitivity of diagnostic tests underestimates the true burden. This study evaluates the diagnostic capabilities of mycology laboratories and the availability of antifungal treatments in Peruvian healthcare facilities to identify gaps and improve IFI management. An observational, cross-sectional study was conducted online targeting physicians involved in IFI management across multiple centers in Peru, from April 2023 to April 2024. The survey covered institutional profiles, incidence and perceived relevance of IFI, diagnostic tools, and access to antifungal drugs. Fifty-four centers from 21/24 departments (Peruvian term for regions) in Peru participated. All centers reported a low to moderate IFI incidence. Candida spp. was the most concerning pathogen (93%), followed by Aspergillus spp. and Cryptococcus spp. (57% each). Diagnostic methods like microscopy were universally used (100%), while culture-based diagnosis was available in 90% of centers. Access to advanced diagnostics for species identification varied, with better availability in the capital (91%) compared to regions (64%). Antibody detection tests were available in 30% of centers, mostly in the capital area. Antigen detection tests were available in 46% of institutions, with significant regional disparities. Imaging techniques were widely used, but surgical access varied. Triazoles were the most accessible antifungals (96%), while echinocandins and therapeutic drug monitoring (TDM) were significantly limited (37% and 2%, respectively). The study highlights disparities in the availability of advanced diagnostics and antifungals in Peru. Despite universal use of microscopy, access to species identification, antibody, and antigen detection tests is limited outside the capital. Ensuring equitable access to these resources and implementing therapeutic drug monitoring are crucial for improving IFI management in Peru. IMPORTANCE Invasive fungal infections are a critical yet often underrecognized public health issue, particularly in countries with diverse climates like Peru. Limited access to advanced diagnostic tools and antifungal treatments creates significant barriers to effective management, contributing to underdiagnosis and delayed care. Our study provides an in-depth evaluation of current diagnostic capabilities and drug availability for IFI across Peru, uncovering geographic disparities and resource gaps that affect patient outcomes. This research highlights the urgent need for policy reforms aimed at enhancing laboratory infrastructure and access to antifungal therapies, ultimately improving IFI management and reducing mortality in Peru and similar regions globally.

Discrimination of Clinical and Food-Derived Candida Strains Using Biotyping and Molecular Typing Approaches

2025-06-20

Katarzyna Rajkowska , Anna Otlewska , Dorota Simińska | Pathogens

Identification and differentiation of Candida spp. yeasts, especially clinically relevant isolates, is of high importance with respect to their origin, pathogenic potential, colonization pattern, and resistance to antimycotics. Currently, numerous … Identification and differentiation of Candida spp. yeasts, especially clinically relevant isolates, is of high importance with respect to their origin, pathogenic potential, colonization pattern, and resistance to antimycotics. Currently, numerous typing methods with varying or unknown discriminatory power are used. This study evaluated the utility of five methods—biotyping using the API system, ITS1 and ITS4 sequence analysis, ITS region polymorphism, multiplex PCR of ITS1, ITS3, and ITS4 regions, and karyotyping—for typing 42 strains differing in origin (24 clinical and 18 food-borne). The highest discriminatory power was obtained for ITS sequencing and karyotyping, both yielding a discrimination index of 1.000. The discrimination indices for other methods ranged from 0.957 for genotyping based on ITS region polymorphism to 0.997 for multiplex PCR-genotyping. Although biotyping showed relatively high discriminatory potential, its use led to misclassification of 64.3% of isolates compared to ITS sequencing. These findings emphasize the importance of applying a typing method with a discrimination index of 1.000 to ensure accurate interpretation of strain-relatedness and origin. Methods with lower indices may reflect methodological limitations rather than actual genetic relatedness. Determining the discrimination index is therefore essential when selecting appropriate tools for yeast typing, particularly in clinical and epidemiological contexts.

Hefen in der Lunge – Kolonisation oder Katastrophe?

2025-06-20

Christian Hohmann , Ludwig Abel-Andrée , Dariusz Peszko +2 more | Medizinische Klinik - Intensivmedizin und Notfallmedizin

Evaluation of a novel aspergillus IgG lateral flow assay for the diagnosis of non-neutropenic patients with acute and subacute invasive aspergillosis

2025-06-20

Yajie Lu , Huanhuan Zhong , Yujie Wang +7 more | Frontiers in Cellular and Infection Microbiology

Purpose This study aimed to assess a novel lateral flow assay (LFA) for Aspergillus IgG detection in patients with non-neutropenic invasive aspergillosis (IA). Methods Aspergillus IgG LFA and enzyme-linked immunosorbent … Purpose This study aimed to assess a novel lateral flow assay (LFA) for Aspergillus IgG detection in patients with non-neutropenic invasive aspergillosis (IA). Methods Aspergillus IgG LFA and enzyme-linked immunosorbent assay (ELISA) were performed in non-neutropenic IA patients and control group (proven community acquired pneumonia and healthy persons), respectively. The diagnostic performance of Aspergillus IgG LFA for IA was evaluated and compared with ELISA method. Results 33 cases of acute IA, 30 cases of subacute IA and 80 controls were enrolled in this study. The level of plasma Aspergillus IgG LFA in the IA group was significantly higher than that in the control group (190.5 AU/mL vs. 50.3 AU/mL, P &lt; 0.001). In total, the sensitivity/specificity/PPV/NPV of Aspergillus IgG LFA was 65.1%/97.5%/95.4%/78.0%. The sensitivity and specificity of Aspergillus IgG LFA were equivalent to those of Aspergillus IgG ELISA with a 120 AU/mL cut-off, but exhibited significantly higher specificity (97.5% vs 87.5%, P = 0.021) compared to the ELISA with an 80 AU/mL cut-off. The consistency was strong among the two methods (P &lt; 0.001, Kappa = 0.67/0.68). The sensitivities/specificities/PPVs/NPVs of Aspergillus IgG LFA were 57.6%/97.5%/90.5%/84.8% for patients with acute IA, and 73.3%/97.5%/91.7%/90.7% for patients with subacute IA, respectively. The “any-positive” strategy, which combined Aspergillus IgG LFA with sputum culture and serum galactomannan (GM), had a sensitivity/specificity/PPV/NPV of 81.1%/94.7%/95.6%/78.3%. The sensitivity/specificity/PPV/NPV of bronchoalveolar lavage fluid (BALF) GM was 65.0%/90.0%/92.9%/56.3%. When combined Aspergillus IgG LFA with BALF GM, the figures were 87.5%/85.0%/92.1%/77.3%. Conclusions Compared to the Aspergillus IgG ELISA, the Aspergillus IgG LFA exhibits comparable or superior diagnostic efficiency in IA patients, while offering a faster and more convenient option for clinical diagnosis. The “any-positive” strategy of combined diagnosis with Aspergillus IgG LFA serves as a valuable supplement to current diagnostic approaches, particularly benefiting patients who cannot tolerate invasive bronchoscopic procedures.

Antifungal Use in Immunocompromised Children in Europe: A 12-Week Multicenter Weekly Point Prevalence Survey (CALYPSO)

2025-06-20

Elisavet Chorafa , Εlias Iosifidis , Andrea Oletto +7 more | Journal of Pediatric Hematology/Oncology

We prospectively analyzed antifungal use in immunocompromised children through a multicenter 12-week weekly point-prevalence survey in 31 hematology-oncology (HO) and hematopoietic stem cell/solid organ transplant (HSCT/SOT) units of 18 hospitals … We prospectively analyzed antifungal use in immunocompromised children through a multicenter 12-week weekly point-prevalence survey in 31 hematology-oncology (HO) and hematopoietic stem cell/solid organ transplant (HSCT/SOT) units of 18 hospitals in 11 European countries. All patients hospitalized and receiving systemic antifungals were included. Ward policies, and weekly ward/patient data were collected. All 21 HO and 10 HSCT/SOT units had prophylaxis policies for high-risk patients (27/31 used azoles, 14/31 echinocandins and 15/31 liposomal amphotericin B [LAMB]). Among 572 courses recorded, prophylaxis was indicated in 439/572 (77%) and treatment in 133/572 (62/133 empirical, 43/133 pre-emptive, 28/133 targeted). Among patients receiving prophylaxis, 56% belonged to the non-high-risk group. Most common reasons for empirical, pre-emptive and targeted treatment were antibiotic-resistant febrile neutropenia (52%), abnormalities on chest-CT with/without positive galactomannan (77%) and candidiasis (82%), respectively. Fluconazole and LAMB were the most frequently prescribed agents both for prophylaxis (31%, 21%) and treatment (32%, 23%). Underdosing of micafungin for treatment in 50% of prescriptions and of fluconazole for treatment and prophylaxis in 70% of cases was noticed. In conclusion, most antifungal prescribing was for prophylaxis, with fluconazole being the main antifungal prescribed. Inadequate doses of antifungal prescribing and prophylaxis of non-high-risk patients could be targets for improvement.

Characterizing neonatal community-acquired invasive fungal infections: Clinical profiles, pathogens, and underlying conditions

2025-06-20

C.A. Gao , Li Wang , Lingkong Zeng +1 more | Medicine

To characterize the clinical presentation and diagnostic indicators of neonatal community-acquired invasive fungal infections and establish a systematic approach for early identification and management. This study retrospectively reviewed the medical … To characterize the clinical presentation and diagnostic indicators of neonatal community-acquired invasive fungal infections and establish a systematic approach for early identification and management. This study retrospectively reviewed the medical records of neonates discharged from the neonatal department between 1/1/2019 and 1/12/2023. Cases were identified based on the primary or first diagnosis using the International Classification of Diseases, 9th Revision codes. A total of 6 patients were included and comprehensive clinical data were analyzed. A systematic literature review (PubMed/Embase, 2000-2023) was conducted to contextualize findings. 6 neonates, including 5 boys, weighed 2700 to 4480 g, hospitalized at the age of 15 to 26 days. Key findings included: Patients had nonspecific respiratory symptoms, such as cough, tachypnea, and fever; the auxiliary examination showed positive β-ᴅ-glucan (cases 1, 4, 5) and galactomannan test (cases 2, 3, 4), and all cases had elevated CD4+/CD8 + ratio; multifocal consolidations (cases 2, 3) with halo sign evolution on serial imaging; pathogen spectrum were: Aspergillus flavus (3/6), Candida spp. (2/6), Lichtheimia corymbifera (1/6); antifungal treatments achieved clinical resolution in all cases (median duration 24 days), with sustained remission at 3-month follow-up; underlying immunometabolic disorders identified post-diagnosis in 83% (5/6) cases, including chronic granulomatous disease, lupus syndrome, and methylmalonic acidemia. Neonatal community-acquired invasive fungal infections represents a critical diagnostic challenge requiring for its low incidence and nonspecific clinical features. Diagnosis mainly based on the fungi-culture. Appropriate use of antifungi medication can lead to a better outcome. Moreover, suspicion of the latent diseases which can cause immune and metabolic dysfunction would be benefit for improving prognosis.

Adjunctive use of posaconazole, hyperbaric oxygen therapy, and methylene blue for COVID-19-associated mucormycosis

2025-06-19

Sujata Mohanty , Neeraj Bansal , Anjali Verma +3 more | Oral and Maxillofacial Surgery

A rare presentation of adrenal histoplasmosis in an immunocompetent patient as an adrenal crisis

2025-06-19

Anita Sarkar , Satya Ranjan Misra , Shuvajit Roy +2 more | Indian Journal of Case Reports

A 44-year-old diabetic male presented with hypovolemic shock along with cough-cold, weakness, and low-grade fever for the past 4 months. On laboratory investigation, there were hyponatremia, hyperkalemia, and hypercalcemia. Persistently … A 44-year-old diabetic male presented with hypovolemic shock along with cough-cold, weakness, and low-grade fever for the past 4 months. On laboratory investigation, there were hyponatremia, hyperkalemia, and hypercalcemia. Persistently low parathyroid levels along with a positive adrenocorticotropic hormone stimulation test confirmed primary Addison’s disease. On ultrasonography, there was a bilateral adrenal mass over which computed tomography-guided fine needle aspiration cytology was done. Periodic acid Schiff stain of the sample showed intracellular yeast cells resembling histoplasmosis and on culture at 25°C it showed microconidia with successful conversion of mycelium to yeast. The patient was treated with Liposomal Amphotericin B over 2 weeks and steroids, with which the patient gradually improved.

Species Distribution and Antifungal Susceptibility Patterns of Invasive Candidiasis in a Belgian Tertiary Center: A 7-Year Retrospective Analysis

2025-06-19

Sarah Cugnata , Rosalie Sacheli , Nathalie Layios +1 more | Journal of Fungi

Candidiasis is a major fungal infection worldwide, with invasive forms linked to high morbidity and mortality. The emergence of azole resistance in Candida parapsilosis causing candidemia led us to examine … Candidiasis is a major fungal infection worldwide, with invasive forms linked to high morbidity and mortality. The emergence of azole resistance in Candida parapsilosis causing candidemia led us to examine the epidemiology and antifungal susceptibility of Candida species at the University Hospital of Liège between January 2017 and December 2023. A total of 916 isolates from blood or sterile body fluids, tissues, and abscesses were analyzed. Species identification was performed using MALDI-TOF MS and antifungal susceptibility testing via Sensititre YO10 AST was interpreted according to the CLSI guidelines. Candida albicans remained the predominant species (56%), followed by Nakaseomyces glabratus (19%), Candida parapsilosis (8%), and Candida tropicalis (7%). No significant shift toward non-albicans Candida species (NAC) was observed even during the COVID-19 pandemic, supporting the use of narrow-spectrum empirical therapy in selected patients. Fluconazole susceptibility was high in C. albicans (98.8%), whereas N. glabratus and C. tropicalis showed high resistance rates with 10.1% and 16.9%, respectively. C. parapsilosis showed stable fluconazole susceptibility across the study period. Echinocandins demonstrated excellent activity (95.6-100%), and amphotericin B was effective against nearly all isolates. This seven-year surveillance at the University Hospital of Liège confirms that while C. albicans remains the predominant and highly susceptible species, rising azole resistance in non-albicans Candida-particularly N. glabratus and C. tropicalis-highlights the critical need for ongoing local epidemiological monitoring to guide effective and targeted antifungal therapy.

Home sputum collection forAspergillus fumigatusdetection in adults with cystic fibrosis

2025-06-19

Gina Hong , J. B. Walsh , Abraham Koshy +7 more | ERJ Open Research

Background Elexacaftor/tezacaftor/ivacaftor (ETI) has impacted the ability for people with cystic fibrosis (PwCF) to spontaneously expectorate sputum leading to lower respiratory sampling rates and infection detection challenges. Home sampling may … Background Elexacaftor/tezacaftor/ivacaftor (ETI) has impacted the ability for people with cystic fibrosis (PwCF) to spontaneously expectorate sputum leading to lower respiratory sampling rates and infection detection challenges. Home sampling may permit a potential strategy for fungal detection in PwCF. Methods We conducted a prospective decentralized cohort study of PwCF to test the feasibility of home sputum collection and ambient temperature transport for Aspergillus fumigatus ( Af ) detection. Participants collected and shipped weekly sputum samples from home to the laboratory for fungal culture and completed electronic questionnaires. Descriptive statistics were calculated for patient factors, sputum characteristics, and Af positive cultures. We used a generalized estimating equations model to determine the association between highly effective modulator therapy (HEMT) and sputum volume. Results We enrolled 76 adults with cystic fibrosis (CF) with a median FEV 1 percent predicted of 72.5 [53.8, 86.3] %. Sixty (79%) were on ETI and 44 (58%) had a history of Aspergillus . Seventy (92%) successfully collected and shipped three or more sputum samples. Of 284 samples received, 83% arrived within one day. Sputum collection was reported as easy in 83 (29%) and somewhat easy in 114 (40%) collection events. Sputum volume from PwCF on HEMT was 36% lower than those not on HEMT (36%, 95% CI 3%, 58%, p=0.03), adjusting for covariates. Af was detected in 205 (73%) home sputum samples. Conclusion Home sputum collection is feasible in adults with CF. Af was detected in remotely collected sputum samples. Further work to assess the validity of home sputum samples in PwCF is necessary to determine the value of remote specimens in clinical and research settings.

New Therapeutic Options for Fusariosis: A Patent Review (2008–2023)

2025-06-18

Izadora Dillis Faccin , Túlio Máximo Salomé , Gleyce Hellen de Almeida de Souza +6 more | Journal of Fungi

Fusariosis is an infection caused by the fungus Fusarium spp., which is pathogenic to both plants and humans. The disease presents several clinical manifestations and epidemiological patterns. Current treatment relies … Fusariosis is an infection caused by the fungus Fusarium spp., which is pathogenic to both plants and humans. The disease presents several clinical manifestations and epidemiological patterns. Current treatment relies on azoles and polyenes, but increasing antifungal resistance requires the exploration of new therapeutic options. This study reviewed patents related to the treatment of Fusariosis from the last 15 years (up to June 2023). The search identified 318 patents, categorized by identification code, publication date, type of application and mechanism of action, using the International Patent Classification and Cooperative Patent Classification systems. In addition, we conducted a bibliographic search in the PubMed database using the same criteria to identify the number of scientific articles. Of the 318 patents, 21 targeted Fusarium infections in humans. The years 2014 and 2018 stood out with three patents each, while the same period recorded an average of 58 published articles. The patents addressed mechanisms such as drug delivery, gene expression, immunotherapy, engineered drugs, and novel compounds. This research highlights the urgent need for continued innovation in therapeutic technologies to effectively treat Fusarium wilt.

Detection of Mucorales antigen in bronchoalveolar lavage samples using a newly developed lateral-flow device

2025-06-18

Julie Rousselot , Laurence Millon , Émeline Scherer +7 more | Journal of Clinical Microbiology

ABSTRACT A murine IgG2b monoclonal antibody, named TG11, binding to an extracellular polysaccharide antigen secreted by all Mucorales fungi has been recently developed and integrated into a lateral-flow device (TG11-LFD). … ABSTRACT A murine IgG2b monoclonal antibody, named TG11, binding to an extracellular polysaccharide antigen secreted by all Mucorales fungi has been recently developed and integrated into a lateral-flow device (TG11-LFD). The aim of this study was to establish the clinical performance of TG11-LFD on bronchoalveolar lavage (BAL) fluids for the diagnosis of mucormycosis. Thirteen BAL samples from 13 patients with mucormycosis, all of which tested positive for Mucorales qPCR ( Mucor/Rhizopus [ n = 5], Lichtheimia [ n = 2], Rhizomucor [ n = 5], and Cunninghamella [ n = 1]), were used to assess the TG11-LFD. We also selected 49 BAL samples from 25 patients with other invasive fungal infections (IFI) (aspergillosis, Pneumocystis infection, candidiasis, and possible IFI) and from 20 patients without IFI for use as negative controls. The intensities of the test and control lines were recorded using a Cube reader. The diagnostic performance was assessed by analyzing the receiver operating characteristics (ROC) curve with the Jamovi software package (version 2.6.13). The area under the curve of the ROC curve was 0.739. Using a threshold value positivity ≤531 artificial units, the TG11-LFD test has a sensitivity and specificity of 76.92% and 75.51%, respectively, a positive predictive value of 45.45%, and a negative predictive value of 92.5%. In this study, we evaluated the performance of TG11-LFD on clinical samples for the first time and demonstrated its significant potential for enhancing the rapid detection of mucormycosis. Combining antigen detection with qPCR, as successfully applied in the diagnosis of aspergillosis, is likely to yield the most reliable diagnostic approach. IMPORTANCE Mucormycosis is a severe emerging, invasive fungal disease caused by fungi in the order Mucorales . The mortality rate remains high at approximately 50%. Rapid diagnosis and prompt initiation of targeted treatment are associated with an improved prognosis. Gold standard diagnostic procedures have poor sensitivity and long turnaround times. Mucorales polymerase chain reaction in blood and respiratory samples has improved diagnosis, but this technique is not widely available due to high costs and the need for specialist equipment. A prototype lateral-flow device (TG11-LFD) incorporating a mouse monoclonal antibody, which binds to an extracellular polysaccharide antigen specific to Mucorales fungi, has been recently developed. In this study, we evaluated for the first time the performance of the TG11-LFD test on clinical bronchoalveolar lavage fluids for diagnosing mucormycosis. With 76.92% sensitivity and 75.51% specificity, this innovative, simple, and affordable approach shows great potential for improving the rapid diagnosis of mucormycosis.

Mitochondrial anchor protein Num11 is key to pathogenicity of Candida albicans by affecting mitochondrial function and cell wall masking

2025-06-18

Guangyuan Yang , Xiaojia Niu , Tian Zhuang +7 more | Virulence

The mitochondrial anchoring protein Num1 directly affects mitochondrial redox function, cell division, and growth in unicellular fungi. However, the functional characterization of Num11, its Candida albicans homolog, remains elusive. Our … The mitochondrial anchoring protein Num1 directly affects mitochondrial redox function, cell division, and growth in unicellular fungi. However, the functional characterization of Num11, its Candida albicans homolog, remains elusive. Our investigation revealed that Num11 deletion in C. albicans caused profound cellular defects: (1) Disrupted cell cycle progression and mitochondrial dysfunction manifesting as mitochondrial morphological aggregation, ATP depletion, membrane potential collapse, and ROS overproduction; (2) Hypersensitivity to cell wall-perturbing agents accompanied by thicker cell walls and increased surface exposure of β-glucan/chitin; (3) Enhanced macrophage phagocytosis and proinflammatory cytokine release. These cellular alterations translated to significantly attenuated virulence in both Galleria mellonella and systematic mice infection models. Mechanistically, transcriptome profiling and protein interaction analyses demonstrated Num11 deficiency hyperactivates the Cdc42-Cek1 MAPK cascade (phospho-Cek1 increased), driving cell wall remodeling. Our findings establish Num11's dual closely connected regulatory roles in C. albicans pathogenesis: as a mitochondrial scaffold maintaining bioenergetic homeostasis to attenuate growth and as a negative regulator of the Cdc42-Cek1 axis controlling cell wall architecture through affection on mitochondria. These coordinated actions collectively underscore Num11's critical role in mediating host-pathogen interactions during invasive candidiasis.

Impact of CD11c+ cells in conducting airway lumen on Aspergillus fumigatus conidia deposition in neutropenic mice

2025-06-18

Mariia V. Pavelchenko , Svyatoslav Shalyapin , Sergey Portnov +6 more | Frontiers in Fungal Biology

Introduction Inhaled conidia of the opportunistic fungi Aspergillus fumigatus settle in the airway mucosa and in alveolar spaces. Different immune cells typically provide crucial defense against fungal germination. However, in … Introduction Inhaled conidia of the opportunistic fungi Aspergillus fumigatus settle in the airway mucosa and in alveolar spaces. Different immune cells typically provide crucial defense against fungal germination. However, in immunocompromised patients, the lack of sufficient pro-inflammatory immune response often leads to invasive aspergillosis, with current treatments being limited by insufficient understanding of the precise conidial distribution patterns in the airways. Methods Therefore, we employed advanced imaging techniques, including immunohistochemistry, optical clearing, and confocal laser scanning microscopy, to map A. fumigatus conidial distribution in both immunocompetent and neutropenic mouse airways. We developed a 3D airway model distinguishing the main bronchus, intermediate bronchi, and terminal bronchioles, enabling quantitative analysis of conidial location. In addition, we analyzed the interactions of CD11c + cells with conidia in the conducting airway mucosa. Results Our findings revealed that while the majority of conidia reached the alveolar space in both groups, neutropenic mice showed significantly higher conidial concentrations in bronchial branches, particularly in the main bronchus, compared with immunocompetent mice. Simultaneously, in the conducting airway mucosa of neutropenic mice, CD11c + cells ingested an elevated number of conidia compared with immunocompetent mice. Discussion Thus, detailed mapping of the conidial distribution patterns provides crucial insights into the spatial aspects of antifungal treatment in neutropenic patients. The enhanced contribution of CD11c + cells to conidial internalization in the conducting airway mucosa of neutropenic mice demonstrated in the present study emphasizes the potential of these cells in the development of more effective, cell-targeted antifungal treatments.

SARS-CoV-2 coinfection in patients with invasive pulmonary aspergillosis: clinical characteristics and prognosis

2025-06-18

Mengshu Xie , Xiaofeng Zhu , Ao Ma +6 more | Annals of Clinical Microbiology and Antimicrobials

COVID-19 associated pulmonary aspergillosis (CAPA) has been globally reported to be a life-threatening complication of severe COVID-19. Previous studies primarily focused on an association between secondary Aspergillus infection and elevated … COVID-19 associated pulmonary aspergillosis (CAPA) has been globally reported to be a life-threatening complication of severe COVID-19. Previous studies primarily focused on an association between secondary Aspergillus infection and elevated mortality risk in COVID-19 patients, while potential confounding factors and alternative pathogenic mechanisms remain insufficiently investigated. The risk factors and outcomes of patients with secondary SARS-CoV-2 infection following invasive pulmonary aspergillosis (IPA) were not been well explored either. This retrospective monocentric study enrolled 152 hospitalized IPA patients with and without SARS-CoV-2 infection from 1 November 2022 to 31 October 2023. The characteristics of IPA patients and related risk factors were investigated, and the relationship between different SARS-CoV-2 infection status and the prognosis in IPA patients was further evaluated. Our analysis demonstrated that IPA patients subsequently diagnosed with SARS-CoV-2 infection exhibited significantly elevated mortality risk compared to those without viral coinfection (53.6% vs. 22.9%, P < 0.001). SARS-CoV-2 infection status (OR 3.708; P = 0.001; 95%CI 1.674-8.212), albumin concentration (OR 0.885; P = 0.005; 95%CI 0.813-0.964), and C-reactive protein level (OR 1.007; P = 0.012; 95%CI 1.002-1.013) were statistically significant independent risk factors for prognosis of IPA patients. Subsequent analysis established a multivariate risk prediction model incorporating independent prognostic factors, which exhibited robust discriminative capacity for mortality risk stratification via ROC curve validation (AUC = 0.792, 95%CI 0.721-0.862, P < 0.0001). A statistically significant difference in mortality rate existed between IPA patients with secondary SARS-CoV-2 infection and CAPA patients (63.2% and 33.3%, P = 0.037). Notably, comparative analysis revealed no statistically significant differences in 28-day (22/96, 22.9% vs. 6/18, 33.3%) or 90-day mortality rates (22/96, 22.9% vs. 6/18, 33.3%) between patients with IPA without SARS-CoV-2 infection and IPA patients with secondary SARS-CoV-2 infection. IPA patients with secondary SARS-CoV-2 coinfection had a lower mortality compared to those with CAPA. Considering the high mortality rate, more medical cares are needed for these patients.

Aggregation and biofilm formation of mono- and co-culture Candida species and Staphylococcus aureus are affected by nutrients in growth media

2025-06-18

Wan NurHazirah Wan Ahmad Kamil , Mukarramah Zainal , Munirah Mokhtar +3 more | Biofouling

Candida species and Staphylococcus aureus coexist in nosocomial infections. These interkingdom interactions are associated with oral biofilm formation, leading to various oral diseases. This study elucidated the interkingdom interactions of … Candida species and Staphylococcus aureus coexist in nosocomial infections. These interkingdom interactions are associated with oral biofilm formation, leading to various oral diseases. This study elucidated the interkingdom interactions of these microorganisms, particularly their aggregation and biofilm formation, in three different media. Candida auris, Candida albicans, Candida lusitaniae, Candida dubliniensis, Candida parapsilosis, Candida glabrata and S. aureus were used in this study. Aggregation assays were conducted to determine planktonic interaction, and biofilm assays were performed to investigate intra- and interkingdom interactions in a static biofilm environment. Most Candida spp. exhibited a high auto-aggregation percentage in brain heart infusion broth supplemented with yeast extract (BHIYE). In addition, co-culture biofilm with S. aureus significantly reduced the total cell counts of Candida spp. compared to mono-culture (p < 0.05). In conclusion, co-aggregation, biofilm biomass and total cell count were species- and growth medium-dependent, and S. aureus interacted antagonistically with Candida spp.

Time for an Update? Fungal Infection Trends and Practices With Mechanical Circulatory Support

2025-06-18

Mark Liotta , Virginia Gonzalez , Claire Zurlo +6 more | ASAIO Journal

A benchmark dataset for validating FKS1 mutations in Candida auris

2025-06-18

Elizabeth Misas , Lindsay A. Parnell , Malavika Rajeev +7 more | Microbiology Spectrum

ABSTRACT Echinocandins are the recommended antifungal therapy for Candida auris infections in many countries. While echinocandin resistance remains uncommon, recent reports demonstrate an increase in such cases, with the potential … ABSTRACT Echinocandins are the recommended antifungal therapy for Candida auris infections in many countries. While echinocandin resistance remains uncommon, recent reports demonstrate an increase in such cases, with the potential for echinocandin-resistant C. auris transmission between persons. The expansion of C. auris whole-genome sequencing capacity in public health laboratories provides a great opportunity to leverage genomic data to detect echinocandin resistance-conferring mutations. However, curated datasets for validating genomic tools for these purposes are lacking. Therefore, we developed a benchmark dataset comprising 100 whole-genome sequenced C. auris isolates categorized as echinocandin-susceptible ( n = 53) and resistant ( n = 47) by antifungal susceptibility testing. We implemented the fungal bioinformatics pipeline, MycoSNP-nf, to perform whole-genome sequencing analysis, including C. auris clade typing and the detection of FKS1 mutations in hotspot (HS) regions. Phylogenetic analysis classified isolates into four major clades (Clades I–IV). Of the 47 isolates considered resistant by AFST, 44 showed HS mutations identified by MycoSNP-nf—with 41 positioned in two well-described HS regions and 3 within a potential third hotspot that was recently reported. This benchmark dataset is designed to be a resource to build sequencing capacity to detect echinocandin resistance-conferring mutations in FKS1 and to help standardize comparisons across other bioinformatics tools. IMPORTANCE Echinocandins are the recommended first-line treatment for invasive infections caused by Candida auri s, a multi-drug-resistant yeast that has emerged in healthcare facilities globally. Increasing instances of echinocandin-resistant cases highlight the need for rapid detection and response. We developed a benchmark dataset comprising 100 C. auris echinocandin-resistant and -susceptible isolates to demonstrate the utility of the bioinformatics tool, MycoSNP-nf, for detecting echinocandin resistance-related FKS1 mutations and to assess their concordance with antifungal susceptibility testing results. This benchmark may help validate MycoSNP-nf and other bioinformatics tools aimed at detecting these mechanisms using whole-genome sequencing data.