4.6 Article

The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Microbiology

Olorofim Susceptibility Testing of 1,423 Danish Mold Isolates Obtained in 2018-2019 Confirms Uniform and Broad-Spectrum Activity

Karen Marie Thyssen Astvad et al.

Summary: Olorofim, a novel antifungal drug, demonstrates promising activity against various molds but is less effective against Mucorales. This study investigated the susceptibility of different mold isolates, providing essential data for future epidemiological research.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Immunology

Rezafungin Versus Caspofungin in a Phase 2, Randomized, Double-blind Study for the Treatment of Candidemia and Invasive Candidiasis: The STRIVE Trial

George R. Thompson et al.

Summary: The study findings demonstrate that Rezafungin is effective and safe for the treatment of candidemia and/or invasive candidiasis, with high cure rates and clinical responses.

CLINICAL INFECTIOUS DISEASES (2021)

Editorial Material Immunology

Invasive Fungal Disease Complicating Coronavirus Disease 2019: When It Rains, It Spores

Martin Hoenigl

CLINICAL INFECTIOUS DISEASES (2021)

Article Infectious Diseases

Investigational Agents for the Treatment of Resistant Yeasts and Molds

Garret T. Seiler et al.

Summary: This review provides an overview of investigational antifungals in clinical development aimed at addressing the increasing drug resistance patterns. It discusses the pharmacodynamics, spectrum of activity, preclinical studies, and latest clinical trial data of these antifungals. The review highlights the need for continual efforts to discover new antifungals to combat the emergence of multidrug-resistant fungi.

CURRENT FUNGAL INFECTION REPORTS (2021)

Article Microbiology

Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis Pneumonia

Lynn Miesel et al.

Summary: Rezafungin, a novel echinocandin, has shown efficacy against Candida, Aspergillus, and Pneumocystis in prophylactic studies. By reducing fungal burden and preventing infection, it has the potential to be a single-agent prophylaxis against invasive fungal diseases caused by these pathogens.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Infectious Diseases

In vitro activity of the novel antifungal olorofim against dermatophytes and opportunistic moulds including Penicillium and Talaromyces species

Ashutosh Singh et al.

Summary: Olorofim demonstrates potent in vitro activity against drug-resistant dermatophytes and opportunistic moulds, with exceptions in Alternaria alternata. When compared to other systemic antifungal drugs, Olorofim exhibits lower activity against Penicillium and Talaromyces species. Particularly, Olorofim shows strong activity against Trichophyton isolates, including those resistant to terbinafine and azoles.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

Article Pharmacology & Pharmacy

Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent

Lindsey Cass et al.

Summary: PC945 is a novel antifungal triazole for nebulized delivery to treat lung Aspergillus infections. Pharmacokinetics and safety profiles were characterized in healthy subjects and subjects with mild asthma. PC945 showed high lung concentrations and specific inhibition of CYP3A4/5 substrate metabolism.

PHARMACOLOGY RESEARCH & PERSPECTIVES (2021)

Review Microbiology

Potency of Olorofim (F901318) Compared to Contemporary Antifungal Agents against Clinical Aspergillus fumigatus Isolates and Review of Azole Resistance Phenotype and Genotype Epidemiology in China

Huilin Su et al.

Summary: Triazole resistance in Aspergillus fumigatus is a global problem, requiring new antifungal drugs like olorofim that show efficacy against triazole-resistant strains. In China, TRAF rates range from 2.5% to 5.56% for clinical isolates, with predominant resistance mechanisms being TR34/L98H/S297T/F495I and TR34/L98H mutations. Continuous surveillance and novel drug targets are essential for managing TRAF in China.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Infectious Diseases

Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology

Martin Hoenigl et al.

Summary: With an increasing number of patients requiring intensive care or being immunosuppressed, infections caused by molds other than Aspergillus spp or Mucorales are on the rise. Antifungal prophylaxis has been effective, but breakthrough infections by other rare molds are also increasing. Regional differences should be considered in providing practical clinical decision guidance.

LANCET INFECTIOUS DISEASES (2021)

Review Immunology

Ibrexafungerp, a Novel Oral Triterpenoid Antifungal in Development: Overview of Antifungal Activity Against Candida glabrata

Ahmed Gamal et al.

Summary: Systemic infections caused by Candida glabrata pose a significant threat to both immunocompromised and non-immunocompromised patients, with increasing resistance to traditional antifungal therapies. Ibrexafungerp, a first-in-class glucan synthase inhibitor, shows promising broad-spectrum activity against C. glabrata, including drug-resistant strains, and has potential for treating vulvovaginal candidiasis. Further preclinical and clinical studies are needed to explore its mechanisms and evaluate its efficacy as a new agent for C. glabrata infections.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2021)

Article Microbiology

Manogepix, the Active Moiety of the Investigational Agent Fosmanogepix, Demonstrates In Vitro Activity against Members of the Fusarium oxysporum and Fusarium solani Species Complexes

Hamid Badali et al.

Summary: Manogepix showed good in vitro activity against Fusarium oxysporum and Fusarium solani species complex, while Amphotericin B also demonstrated some activity. Triazoles and micafungin had limited activity in this study.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Microbiology

Antifungal Susceptibility Profiles of Olorofim (Formerly F901318) and Currently Available Systemic Antifungals against Mold and Yeast Phases of Talaromyces marneffei

Jing Zhang et al.

Summary: OLOROFIM exhibits the highest antifungal activity against both mold and yeast phases of Talaromyces marneffei isolates.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Dermatology

In vitro activity of olorofim against clinical isolates of the Fusarium oxysporum and Fusarium solani species complexes

Hamid Badali et al.

Summary: Olorofim showed good in vitro activity against clinical isolates of the Fusarium oxysporum and F solani species complexes, similar to amphotericin B, while other drugs exhibited inconsistent in vitro activity. Further studies are needed to determine its in vivo efficacy.

MYCOSES (2021)

Article Microbiology

A High Rate of Recurrent Vulvovaginal Candidiasis and Therapeutic Failure of Azole Derivatives Among Iranian Women

Amir Arastehfar et al.

Summary: RVVC is a common fungal infection that may be caused by dysbiosis and other factors. FLZR and FLZT phenotypes were found to contribute to fluconazole therapeutic failure, with Iran having a heavy burden of RVVC. Research on RVVC remains limited.

FRONTIERS IN MICROBIOLOGY (2021)

Article Microbiology

In Vitro Activity of Ibrexafungerp against a Collection of Clinical Isolates of Aspergillus, Including Cryptic Species and Cyp51A Mutants, Using EUCAST and CLSI Methodologies

Olga Rivero-Menendez et al.

Summary: Ibrexafungerp, a new orally-available 1,3-beta-D-glucan synthesis inhibitor, demonstrated promising in vitro activity against various clinical isolates of Aspergillus, including azole-resistant strains, with low minimal effective concentrations.

JOURNAL OF FUNGI (2021)

Article Microbiology

Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center

Danilo Y. Thomaz et al.

Summary: This study identified for the first time the environmental sources of ARCP isolates causing persistent clonal outbreaks, which showed resistance to fluconazole. ARCP isolates were associated with a higher crude mortality rate and demonstrated resistance to disinfectants.

JOURNAL OF FUNGI (2021)

Article Microbiology

In Vitro Activity of Novel Antifungal Olorofim against Filamentous Fungi and Comparison to Eight Other Antifungal Agents

Ourania Georgacopoulos et al.

Summary: Olorofim is a novel antifungal drug with promising activity against Aspergillus fumigatus and other molds, regardless of acquired azole resistance. It showed significantly lower MICs compared to echinocandin, azole, and amphotericin B drug classes. Some isolates from Rhizopus spp. and Fusarium spp. were not sensitive to olorofim.

JOURNAL OF FUNGI (2021)

Review Microbiology

Multidrug-resistant Trichosporon species: underestimated fungal pathogens posing imminent threats in clinical settings

Amir Arastehfar et al.

Summary: Species of Trichosporon and related genera are commonly used in biotechnology, but also cause life-threatening invasive trichosporonosis. Understanding of antifungal resistance mechanisms in these fungi is limited, and there is a need for improved treatment strategies.

CRITICAL REVIEWS IN MICROBIOLOGY (2021)

Letter Critical Care Medicine

COVID-19 associated pulmonary aspergillosis: regional variation in incidence and diagnostic challenges

Juergen Prattes et al.

INTENSIVE CARE MEDICINE (2021)

Article Dermatology

ECMM/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries

Shivaprakash M. Rudramurthy et al.

Summary: Globally, the incidence of COVID-19-associated mucormycosis (CAM) is rising, with a significant surge in India. The need to address misconceptions in managing and treating this infection is crucial, with a focus on early suspicion, diagnosis confirmation, glycemic control, surgical debridement, and antifungal therapy. Limited availability of amphotericin B formulations during the epidemic has led to discussions on alternative antifungal therapies.

MYCOSES (2021)

Article Mycology

Aspergillus fumigatus and aspergillosis: From basics to clinics

A. Arastehfar et al.

Summary: The airborne fungus Aspergillus fumigatus poses a serious health threat by causing invasive infections in humans, with frontline azole therapeutics being limited by the emergence of resistant isolates. The search for novel antifungal drugs to combat emerging resistance is ongoing, while advancements in genetic engineering and whole-genome sequencing are being explored to understand and address challenges caused by A. fumigatus.

STUDIES IN MYCOLOGY (2021)

Article Infectious Diseases

Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018-2019)

Michael A. Pfaller et al.

Summary: Manogepix demonstrates potent activity against a wide range of fungal isolates, including drug-resistant strains of Candida and Aspergillus, as well as uncommon fungal species. Its extended spectrum of activity suggests potential therapeutic value in treating difficult-to-treat fungal infections.

JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE (2021)

Article Infectious Diseases

Genetically related micafungin-resistant Candida parapsilosis blood isolates harbouring novel mutation R658G in hotspot 1 of Fks1p: a new challenge?

Amir Arastehfar et al.

Summary: Echinocandin resistance is rare in clinical Candida parapsilosis isolates. A novel mutation in HS1 of FKS1 was identified in echinocandin-resistant isolates, likely leading to in vitro micafungin resistance and in vivo caspofungin therapeutic failure. Close genetic relatedness of isolates suggests clonal expansion as the possible mechanism for the acquisition of echinocandin-resistant C. parapsilosis isolates in naive patients.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

Review Infectious Diseases

Ibrexafungerp: A novel oral glucan synthase inhibitor

M. R. Davis et al.

MEDICAL MYCOLOGY (2020)

Article Infectious Diseases

Madurella mycetomatis, the main causative agent of eumycetoma, is highly susceptible to olorofim

Wilson Lim et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2020)

Review Microbiology

Drug resistance and tolerance in fungi

Judith Berman et al.

NATURE REVIEWS MICROBIOLOGY (2020)

Article Immunology

Hope on the Horizon: Novel Fungal Treatments in Development

Adriana M. Rauseo et al.

OPEN FORUM INFECTIOUS DISEASES (2020)

Article Microbiology

Fosmanogepix (APX001) Is Effective in the Treatment of Pulmonary Murine Mucormycosis Due to Rhizopus arrhizus

Teclegiorgis Gebremariam et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

Article Pharmacology & Pharmacy

Lack of Effect of Rezafungin on QT/QTc Interval in Healthy Subjects

Shawn Flanagan et al.

CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT (2020)

Article Microbiology

Manogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICs

Maiken Cavling Arendrup et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

Review Microbiology

Review of the Novel Investigational Antifungal Olorofim

Nathan P. Wiederhold

JOURNAL OF FUNGI (2020)

Review Microbiology

COVID-19 Associated Pulmonary Aspergillosis (CAPA)-From Immunology to Treatment

Amir Arastehfar et al.

JOURNAL OF FUNGI (2020)

Review Microbiology

The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

Amir Arastehfar et al.

JOURNAL OF FUNGI (2020)

Review Infectious Diseases

Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium

Amir Arastehfar et al.

ANTIBIOTICS-BASEL (2020)

Article Infectious Diseases

Extrapolating Antifungal Animal Data to Humans-Is It Reliable?

Victoria M. Stevens et al.

CURRENT FUNGAL INFECTION REPORTS (2020)

Article Infectious Diseases

In vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies

Olga Rivero-Menendez et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2019)

Article Infectious Diseases

In vitro activity of olorofim (F901318) against clinical isolates of cryptic species of Aspergillus by EUCAST and CLSI methodologies

Olga Rivero-Menendez et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2019)

Article Microbiology

Efficacy of Delayed Therapy with Fosmanogepix (APX001) in a Murine Model of Candida auris Invasive Candidiasis

Nathan P. Wiederhold et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2019)

Article Microbiology

Extended-Interval Dosing of Rezafungin against Azole-Resistant Aspergillus fumigatus

Nathan P. Wiederhold et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2019)

Article Infectious Diseases

In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae

Zoltan Toth et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2019)

Article Microbiology

APX001 Is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis

Teclegiorgis Gebremariam et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2019)

Article Microbiology

APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental Coccidioides immitis Pneumonia

Suganya Viriyakosol et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2019)

Article Immunology

726. APX001 (Fosmanogepix) Is Effective in an Immunosuppressed Mouse Model of Rhizopus oryzae Infection

Teklegiorgis Gebremariam et al.

Open Forum Infectious Diseases (2019)

Article Obstetrics & Gynecology

CD101 Topical Compared With Oral Fluconazole for Acute Vulvovaginal Candidiasis: A Randomized Controlled Trial

Paul Nyirjesy et al.

JOURNAL OF LOWER GENITAL TRACT DISEASE (2019)

Article Microbiology

The Orotomide Olorofim Is Efficacious in an Experimental Model of Central Nervous System Coccidioidomycosis

Nathan P. Wiederhold et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2018)

Article Microbiology

Understanding Echinocandin Resistance in the Emerging Pathogen Candida auris

Milena Kordalewska et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2018)

Article Pharmacology & Pharmacy

In vitro and in vivo Evaluation of APX001A/APX001 and other Gwt1 inhibitors against Cryptococcus

Karen Joy Shaw et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2018)

Article Microbiology

In Vitro and In Vivo Evaluation of the Antifungal Activity of APX001A/APX001 against Candida auris

Christopher L. Hager et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2018)

Article Infectious Diseases

Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method

M. C. Arendrup et al.

CLINICAL MICROBIOLOGY AND INFECTION (2018)

Article Multidisciplinary Sciences

Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia

Alexander Rosenberg et al.

NATURE COMMUNICATIONS (2018)

Article Microbiology

APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method

Maiken Cavling Arendrup et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2018)

Article Microbiology

Safety and Pharmacokinetics of CD101 IV, a Novel Echinocandin, in Healthy Adults

Taylor Sandison et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2017)

Article Infectious Diseases

In vitro activity of the novel antifungal compound F901318 against difficult-to-treat Aspergillus isolates

J. B. Buil et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2017)

Article Infectious Diseases

The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp.

Laura Judith Marcos-Zambrano et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2017)

Article Infectious Diseases

Dihydroorotate dehydrogenase inhibitor F901318 has potent in vitro activity against Scedosporium species and Lomentospora prolificans

Nathan P. Wiederhold et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2017)

Article Infectious Diseases

The global problem of antifungal resistance: prevalence, mechanisms, and management

David S. Perlin et al.

LANCET INFECTIOUS DISEASES (2017)

Article Immunology

APX001A Protects Immunosuppressed Mice from Rhizopus delemar Infection

Teclegiorgis Gebremariam et al.

Open Forum Infectious Diseases (2017)

Article Microbiology

Preclinical Evaluation of the Stability, Safety, and Efficacy of CD101, a Novel Echinocandin

Voon Ong et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2016)

Article Microbiology

Characterization of In Vitro Resistance Development to the Novel Echinocandin CD101 in Candida Species

Jeffrey B. Locke et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2016)

Article Microbiology

Aspergillus fumigatus Intrinsic Fluconazole Resistance Is Due to the Naturally Occurring T301I Substitution in Cyp51Ap

Florencia Leonardelli et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2016)

Article Multidisciplinary Sciences

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

Jason D. Oliver et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Article Multidisciplinary Sciences

Structural mechanism of ergosterol regulation by fungal sterol transcription factor Upc2

Huiseon Yang et al.

NATURE COMMUNICATIONS (2015)

Article Microbiology

Role of FKS Mutations in Candida glabrata: MIC Values, Echinocandin Resistance, and Multidrug Resistance

Cau D. Pham et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2014)

Article Microbiology

Population-Based Survey of Filamentous Fungi and Antifungal Resistance in Spain (FILPOP Study)

A. Alastruey-Izquierdo et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2013)

Article Microbiology

Discovery of a Novel Class of Orally Active Antifungal β-1,3-D-Glucan Synthase Inhibitors

Scott S. Walker et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2011)

Article Infectious Diseases

In vitro activity of a novel broad-spectrum antifungal, E1210, tested against Candida spp. as determined by CLSI broth microdilution method

Michael A. Pfaller et al.

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE (2011)

Article Microbiology

Heteroresistance to Fluconazole in Cryptococcus neoformans Is Intrinsic and Associated with Virulence

Edward Sionov et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2009)

Review Microbiology

Candida albicans cell wall proteins

W. LaJean Chaffin

MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS (2008)

Article Multidisciplinary Sciences

Aneuploidy and isochromosome formation in drug-resistant Candida albicans

Anna Selmecki et al.

SCIENCE (2006)

Article Biochemistry & Molecular Biology

Functional and structural diversity in the Als protein family of Candida albicans

DC Sheppard et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2004)

Review Medicine, General & Internal

Echinocandin antifungal drugs

DW Denning

LANCET (2003)

Article Microbiology

The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro

JC Bowman et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2002)

Article Microbiology

In vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates

S Arikan et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2001)

Article Biochemistry & Molecular Biology

The cell wall architecture of Candida albicans wild-type cells and cell wall-defective mutants

JC Kapteyn et al.

MOLECULAR MICROBIOLOGY (2000)