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Annual Review of Microbiology Sep 2023is a multidrug-resistant fungal pathogen that presents a serious threat to global human health. Since the first reported case in 2009 in Japan, infections have been... (Review)
Review
is a multidrug-resistant fungal pathogen that presents a serious threat to global human health. Since the first reported case in 2009 in Japan, infections have been reported in more than 40 countries, with mortality rates between 30% and 60%. In addition, has the potential to cause outbreaks in health care settings, especially in nursing homes for elderly patients, owing to its efficient transmission via skin-to-skin contact. Most importantly, is the first fungal pathogen to show pronounced and sometimes untreatable clinical drug resistance to all known antifungal classes, including azoles, amphotericin B, and echinocandins. In this review, we explore the causes of the rapid spread of . We also highlight its genome organization and drug resistance mechanisms and propose future research directions that should be undertaken to curb the spread of this multidrug-resistant pathogen.
Topics: Humans; Aged; Candida; Candida auris; Antifungal Agents; Echinocandins; Amphotericin B
PubMed: 37406342
DOI: 10.1146/annurev-micro-032521-015858 -
Journal de Mycologie Medicale Aug 2023Trichophyton indotineae is a newly described dermatophyte species. This fungal pathogen has recently emerged in India and is responsible for chronic or recurrent... (Review)
Review
Trichophyton indotineae is a newly described dermatophyte species. This fungal pathogen has recently emerged in India and is responsible for chronic or recurrent widespread superficial infections. Resistance to terbinafine is frequently associated to this pathogen and is related to point mutations in the gene encoding the squalene epoxidase. T. indotineae infections have been reported outside India, highlighting the risk of worldwide diffusion of this microorganism. Species identification and antifungal susceptibility determination are key points for infection control but still remain challenging. Systemic treatment is usually required and itraconazole is frequently prescribed in case of terbinafine resistance. This review summarizes main features of T. indotineae taxonomy, epidemiology, clinical manifestations, identification, antifungal profile, treatment and prevention.
Topics: Antifungal Agents; Terbinafine; Trichophyton; Drug Resistance, Fungal; Microbial Sensitivity Tests; Arthrodermataceae
PubMed: 37031652
DOI: 10.1016/j.mycmed.2023.101383 -
Molecular Aspects of Medicine Dec 2023Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or... (Review)
Review
Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or super-infections are emerging and have become a rising concern within the last few years. In Europe, cases of candidiasis and aspergillosis dominate, followed by mucormycosis in India. Epidemiological studies show an increasing trend in the incidence of all three entities. Parallel to this, a shift within the underlying fungal pathogens is observed. More non-albicans Candida infections and aspergillosis with cryptic species are on the rise; cryptic species may cover intrinsic resistance to azoles and other antifungal drugs. The recent COVID-19 pandemic led to a significantly increasing incidence of invasive fungal diseases among hospitalized patients.
Topics: Humans; Pandemics; Mycoses; Antifungal Agents; Aspergillosis
PubMed: 37804792
DOI: 10.1016/j.mam.2023.101215 -
Pharmacotherapy Oct 2023Triazole antifungals (i.e., fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) are commonly used in clinical practice to prevent or treat invasive... (Review)
Review
Utility of triazole antifungal therapeutic drug monitoring: Insights from the Society of Infectious Diseases Pharmacists: Endorsed by the Mycoses Study Group Education and Research Consortium.
Triazole antifungals (i.e., fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) are commonly used in clinical practice to prevent or treat invasive fungal infections. Most triazole antifungals require therapeutic drug monitoring (TDM) due to highly variable pharmacokinetics, known drug interactions, and established relationships between exposure and response. On behalf of the Society of Infectious Diseases Pharmacists (SIDP), this insight describes the pharmacokinetic principles and pharmacodynamic targets of commonly used triazole antifungals and provides the rationale for utility of TDM within each agent.
Topics: Humans; Antifungal Agents; Drug Monitoring; Pharmacists; Mycoses; Triazoles; Voriconazole; Communicable Diseases
PubMed: 37459118
DOI: 10.1002/phar.2850 -
Mycoses Sep 2023Isavuconazole is a novel triazole antifungal agent. However, the previous outcomes were highlighted by statistical heterogeneity. This meta-analysis aimed to validate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Isavuconazole is a novel triazole antifungal agent. However, the previous outcomes were highlighted by statistical heterogeneity. This meta-analysis aimed to validate the efficacy and safety of isavuconazole for the treatment and prophylaxis of invasive fungal infections (IFIs) compared with other antifungal agents (amphotericin B, voriconazole and posaconazole).
METHODS
Scopus, EMBASE, PubMed, CINAHL and Ichushi databases were searched for relevant articles that met the inclusion criteria through February 2023. Mortality, IFI rate, discontinuation rate of antifungal therapy and incidence of abnormal hepatic function were evaluated. The discontinuation rate was defined as the percentage of therapy discontinuations due to adverse events. The control group included patients who received other antifungal agents.
RESULTS
Of the 1784 citations identified for screening, 10 studies with an overall total of 3037 patients enrolled. Isavuconazole was comparable with the control group in mortality and IFI rate in the treatment and prophylaxis of IFIs, respectively (mortality, odds rate (OR) 1.11, 95% confidential interval (CI) 0.82-1.51; IFI rate, OR 1.02, 95% CI 0.49-2.12). Isavuconazole significantly reduced the discontinuation rate in the treatment (OR 1.96, 95% CI 1.26-3.07) and incidence of hepatic function abnormalities in the treatment and prophylaxis, compared with the control group (treatment, OR 2.31, 95% CI 1.41-3.78; prophylaxis, OR 3.63, 95% CI 1.31-10.05).
CONCLUSIONS
Our meta-analysis revealed that isavuconazole was not inferior to other antifungal agents for the treatment and prophylaxis of IFIs, with substantially fewer drug-associated adverse events and discontinuations. Our findings support the use of isavuconazole as the primary treatment and prophylaxis for IFIs.
Topics: Humans; Antifungal Agents; Invasive Fungal Infections; Voriconazole; Triazoles
PubMed: 37300337
DOI: 10.1111/myc.13622 -
Advanced Drug Delivery Reviews Jul 2023The growing occurrence of invasive fungal infections and the mounting rates of drug resistance constitute a significant menace to human health. Antifungal drug... (Review)
Review
The growing occurrence of invasive fungal infections and the mounting rates of drug resistance constitute a significant menace to human health. Antifungal drug combinations have garnered substantial interest for their potential to improve therapeutic efficacy, reduce drug doses, reverse, or ameliorate drug resistance. A thorough understanding of the molecular mechanisms underlying antifungal drug resistance and drug combination is key to developing new drug combinations. Here we discuss the mechanisms of antifungal drug resistance and elucidate how to discover potent drug combinations to surmount resistance. We also examine the challenges encountered in developing such combinations and discuss prospects, including advanced drug delivery strategies.
Topics: Humans; Antifungal Agents; Mycoses; Drug Combinations; Drug Resistance, Fungal
PubMed: 37211279
DOI: 10.1016/j.addr.2023.114874 -
Clinical Infectious Diseases : An... Sep 2023Invasive Fusarium infections cause high mortality. Fosmanogepix, a first-in-class antifungal agent, has potent activity against Fusarium. A patient with acute leukemia...
Invasive Fusarium infections cause high mortality. Fosmanogepix, a first-in-class antifungal agent, has potent activity against Fusarium. A patient with acute leukemia with invasive fusariosis, probably involving the central nervous system and caused by Fusarium lactis resistant to currently available antifungal agents, was cured of her infection with fosmanogepix. Fosmanogepix was well tolerated.
Topics: Humans; Female; Antifungal Agents; Fusariosis; Leukemia, Myeloid, Acute; Central Nervous System
PubMed: 37220752
DOI: 10.1093/cid/ciad309 -
Infectious Disease Clinics of North... Sep 2023Recently, there have been significant advances in the diagnosis and management of invasive fungal infections. Compared with traditional fungal diagnostics, molecular... (Review)
Review
Recently, there have been significant advances in the diagnosis and management of invasive fungal infections. Compared with traditional fungal diagnostics, molecular assays promise improved sensitivity and specificity, the ability to test a range of samples (including noninvasive samples, ie, blood), the detection of genetic mutations associated with antifungal resistance, and the potential for a faster turnaround time. Antifungals in late-stage clinical development include agents with novel mechanisms of action (olorofim and fosmanogepix) and new members of existing classes with distinct advantages over existing antifungals in toxicity, drug-drug interactions, and dosing convenience (oteseconazole, opelconazole, rezafungin, ibrexafungerp, encochleated amphotericin B).
Topics: Humans; Antifungal Agents; Mycoses; Invasive Fungal Infections; Drug Resistance, Fungal
PubMed: 37532392
DOI: 10.1016/j.idc.2023.05.001 -
Advanced Drug Delivery Reviews Sep 2023Human pathogenic fungi pose a serious threat to human health and safety. Unfortunately, the limited number of antifungal options is exacerbated by the continuous... (Review)
Review
Human pathogenic fungi pose a serious threat to human health and safety. Unfortunately, the limited number of antifungal options is exacerbated by the continuous emergence of drug-resistant variants, leading to frequent drug treatment failures. Recent studies have also highlighted the clinical importance of other modes of fungal survival of antifungal treatment, including drug tolerance and persistence, pointing to the complexity of the fungal response to antifungal drugs. A lack of understanding of the fungal drug response has hampered the identification of new targets, the development of alternative antifungal strategies and the design of appropriate delivery systems. In this review we summarize recent advances in the study of antifungal resistance, tolerance and persistence, with an emphasis on promising drug targets and drug delivery systems that may yield important insights into the development of new or improved antifungal therapies against fungal infections.
Topics: Humans; Antifungal Agents; Mycoses; Fungi; Drug Tolerance; Drug Delivery Systems
PubMed: 37437715
DOI: 10.1016/j.addr.2023.115007 -
Biomolecules Oct 2023Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited antifungal range,... (Review)
Review
Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited antifungal range, inadequate safety profiles, and low oral bioavailability. Consequently, there is an urgent imperative to develop novel antifungal medications for clinical application. This comprehensive review provides a summary of the antifungal properties and mechanisms exhibited by natural polyketides, encompassing macrolide polyethers, polyether polyketides, xanthone polyketides, linear polyketides, hybrid polyketide non-ribosomal peptides, and pyridine derivatives. Investigating natural polyketide compounds and their derivatives has demonstrated their remarkable efficacy and promising clinical application as antifungal agents.
Topics: Humans; Antifungal Agents; Polyketides; Macrolides; Peptides
PubMed: 38002254
DOI: 10.3390/biom13111572