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1.
The high morbidity, mortality, and healthcare costs associated with the invasive fungal infections, especially in the critical care setting, is of importance since the prophylactic, empiric, and pre-emptive therapy interventions, based on early identification of risk factors, is of common occurrence. In the last years alone there have been important developments in antifungal pharmacotherapy. Evidence-based studies using new antifungal agents are now emerging as important players in the pharmacotherapy of invasive fungal infections in seriously ill and difficult patients. However, data on critically ill patients are more limited and usually recovered from general studies. This study shows the benefits obtained by the new antifungal agents on different clinical situations in critical care units. The increasing number of non-C. albicans species and the high mortality rates in these settings suggest that the application of early de-escalation therapy in critically ill patients with fungal infection should be mandatory. The possibility of using antifungal combination therapy in these types of patients should be considered. 相似文献
2.
近年来,真菌感染患者的发病率和死亡率持续上升,但现有抗真菌药物种类依然非常少,并且耐药现象的出现使临床可选择的抗真菌药物变得更加有限.因此,对新的抗真菌药物的开发迫在眉睫,从天然产物中寻找新型高效的抗真菌药物成为目前的研究热点之一.从天然产物中筛选出具有抗真菌活性的天然化合物,有助于扩大治疗真菌感染疾病的可选药物种类,减少耐药的发生.该文归纳现有报道的具有抗真菌活性的化合物,根据其不同来源及不同化学结构进行分类,阐明不同类别天然化合物的抗真菌作用机制,为开发新型高效抗真菌药物提供前体结构及抗真菌新靶点. 相似文献
3.
The improved survival of fragile pediatric hosts such as those afflicted with primary or acquired immune deficiencies, prematurity, and surgical pathology – mainly gastrointestinal and trauma – has resulted in an increased number of children susceptible to invasive fungal infections. These infections are associated with significant morbidity and mortality. Newer, safer antifungal agents allow for preventive and empiric strategies in the management of patients at risk, such as premature infants, patients receiving chemotherapy, and bone marrow or solid-organ transplant recipients. Improved radiological and molecular techniques result in earlier diagnosis of fungal infections, allowing for preemptive therapy in these patients, minimizing exposure to antifungal agents and the risk of emergence of resistant fungal strains. A better understanding of the differences in pharmacokinetics between children and adults will allow for better utilization of existing antifungal agents and improved outcomes. 相似文献
4.
A.M. Fuentefria B. Pippi D.F. Dalla Lana K.K. Donato S.F. de Andrade 《Letters in applied microbiology》2018,66(1):2-13
Undeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy.
Significance and Impact of the Study
The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored here, focusing on new agents as well as innovative approaches, such as combination therapy between antifungal drugs or with natural compounds. 相似文献5.
Fungal infections remain a challenge to clinicians due to the limited available antifungals. With the increasing use of antifungals in clinical practice, drug resistance has been emerging continuously, especially to fluconazole (FLC). Thus, a search for new antifungals and approaches to overcome antifungal resistance is needed. However, the development of new antifungals is usually costly and time consuming; discovering the antifungal activity of non-antifungal agents is one way to address these problems. Interestingly, some researchers have demonstrated that several classes of immunosuppressants (calcineurin inhibitors, glucocorticoids, etc) also displayed potent antifungal activity when used alone or in combination with antifungals, especially with FLC. Some of them could increase FLC's susceptibility against resistant Candida albicans significantly reversing fungal resistance to FLC. This article reviews the antifungal activities of immunosuppressants used alone or in combination with antifungals and their potential antifungal mechanisms that have been discovered so far. Although immunosuppressive agents have been identified as risk factors for fungal infection, we believe these findings are very important for overcoming drug resistance and developing new antifungals. 相似文献
6.
Invasive fungal infections are becoming increasingly important in the management of critically ill and immunocompromised patients.
As organ and stem cell transplantation becomes more prominent and immune therapies are employed for diseases such as rheumatoid
arthritis and plaque psoriasis, the population of patients at risk continues to grow. Many invasive fungal infections are
associated with extremely high mortality rates. Antifungal options are limited and novel therapies are intriguing as we attempt
to improve patient outcomes and preserve the antifungal armamentarium. Many other classes of pharmaceuticals typically seen
as non-antifungal do in fact have significant antifungal activity. Prominent among these are calcineurin inhibitors, antiarrhythmics,
antidepressants, antibacterials, and others. Some have activity alone and some augment the activity of conventional antifungals.
Unfortunately, clinical data are lacking for most of these agents and their role in therapy remains undefined. This review
focuses on several representative non-antifungal agents with antifungal activity. 相似文献
7.
《Revista iberoamericana de micología》2021,38(2):84-90
The treatment of invasive fungal infections remains a challenge, both for the diagnosis and for the need of providing the appropriate antifungal therapy. Candida auris is a pathogenic yeast that is responsible for hospital outbreaks, especially in intensive care units; it is characterized by a high resistance to the antifungal agents and can become multidrug-resistant. At present, the recommended antifungal agents for the invasive infections with this pathogen are echinocandins, always after carrying out an antifungal susceptibility testing. In case of no clinical response or persistent candidemia, the addition of liposomal amphotericin B or isavuconazole may be considered. Both fungal infection of the central nervous system and that associated with biomedical devices remain rare entities affecting mainly immunocompromised patients. However, an increase in their incidence in recent years, along with high morbidity and mortality, has been shown. The treatment of these infections is conditioned by the limited knowledge of the pharmacokinetic properties of antifungals. A better understanding of the pharmacokinetic and pharmacodynamic parameters of the different antifungals is essential to determine the efficacy of the antifungal agents in the treatment of these infections. 相似文献
8.
Invasive fungal infections are important causes of morbidity and mortality in critically ill non neutropenic patients. For many years, amphotericin B and flucytosine have been the only available antifungal agents for invasive fungal infections. Fortunately, the antifungal armamentarium has increased during the past two decades with the addition of several new agents. In addition to itraconazole and fluconazole, lipid formulations of amphotericin B, voriconazole, and caspofungin have been recently licensed. These various antifungal agents differ in their pharmacokinetic and pharmacodynamic profile. 相似文献
9.
Georgopapadakou NH 《Current opinion in microbiology》1998,1(5):547-557
Serious fungal infections, caused mostly by opportunistic species, are increasingly common in immunocompromised and other vulnerable patients. The use of antifungal drugs, primarily azoles and polyenes, has increased in parallel. Yet, established agents do not satisfy the medical need completely: azoles are fungistatic and vulnerable to resistance, whereas polyenes cause serious host toxicity. Drugs in clinical development include echinocandins, pneumocandins, and improved azoles. Promising novel agents in preclinical development include several inhibitors of fungal protein, lipid and cell wall syntheses. Recent advances in fungal genomics, combinatorial chemistry, and high-throughput screening may accelerate the antifungal discovery process. 相似文献
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11.
Thomas Lehrnbecher Konrad Bochennek Dominik Schrey Andreas H. Groll 《Current fungal infection reports》2011,5(2):103-110
Invasive fungal infections still play a major role in morbidity and mortality in pediatric patients, especially in children
undergoing therapy for an underlying malignancy and in preterm infants. Relative to the adult population, pediatric age groups
display important differences not only in host biology, predisposing conditions, epidemiology, and presentation of fungal
infections, but also in the disposition and clearance of antifungal compounds. During the past decade, several new antifungal
agents have been developed. Although not all of these agents are yet approved for children, the pediatric development of antifungal
agents has moved forward in an exemplary manner, which is essential for the successful management of the individual patient.
This article reviews the current data on pharmacokinetics, safety, and dosing of antifungal agents in pediatric patients. 相似文献
12.
Brunella Posteraro Patrizia Posteraro Maurizio Sanguinetti 《Current fungal infection reports》2013,7(3):224-234
Candida and Aspergillus species are important causes of opportunistic infection in an ever-growing number of vulnerable patients, and these infections are associated with high mortality. This has partly been attributed to the emerging resistance of pathogenic fungi to antifungal therapy, which potentially compromises the management of infected patients. Multi-azole resistance of Aspergillus fumigatus is a current health problem, as well as is the co-resistance of Candida glabrata to both azoles and echinocandins. In most cases, negative clinical consequences of reduced in vitro fungal susceptibility to azoles and/or echinocandins can be traced to acquisition of particular resistance mechanisms. While strategies using antifungal combinations or adjunctive agents that maximize the efficacy of existing antifungals may limit treatment failures, new therapeutic approaches, including antifungal agents with novel mechanisms of action, are urgent. In the meantime, more efforts should be devoted to close monitoring of antifungal resistance and its evolution in the clinical setting. 相似文献
13.
近年来,随着广谱抗生素,免疫抑制剂,抗肿瘤化疗药物的广泛应用,器官移植的普遍开展以及AIDS患者的逐年增加,各系统侵袭性真菌感染日益增多。抗真菌药物的大量应用使得真菌耐药现象日渐严重。大量研究表明,耐药真菌细胞膜上外排转运蛋白的过量表达对抗真菌药物耐药形成起到重要作用。ATP结合盒式蛋白(ABC转运体)和易化扩散载体超家族蛋白(MFS转运体)便是其中最重要的两种。本文从ABC及MFS转运体的结构和功能出发,分析其在抗真菌药物耐药形成中的作用,并对相关研究进展进行综述。 相似文献
14.
Andreas H. Groll Emmanuel Roilides Thomas J. Walsh 《Current fungal infection reports》2008,2(1):49-56
Pediatric age groups display important differences in host biology, predisposing conditions, epidemiology, and presentation
of fungal infections relative to the adult population. Over the past decade, major advances have been made in the field of
medical mycology. Most importantly, an array of new antifungal agents has entered the clinical arena. Although pediatric approval
of several of these agents remains to be established, the pediatric development of antifungal agents is moving forward. Invasive
fungal infections will remain important causes for morbidity and mortality in immunocompromised pediatric patients. Although
the availability of new therapeutic options is an important advance, antifungal therapy has become increasingly complex, and
a thorough understanding of the available antifungal armamentarium is essential for the successful management of individual
patients. 相似文献
15.
Sarah M. Wieczorkiewicz Jacqueline Jourjy Larry Danziger 《Current fungal infection reports》2009,3(2):103-110
The incidence and severity of invasive fungal infections are on the rise and they pose a risk of significant morbidity and
mortality. The cost burden of fungal infections in the United States is high. There are many newer, less toxic antifungal
agents to manage these challenging infections; however, these agents also carry a high cost of their own. When considering
an antifungal agent for a specific patient, it is important to consider safety, efficacy, and cost, thus making it essential
to continually evaluate the antifungal pharmacoeconomic literature to assist in the therapeutic decision-making process for
patients with invasive fungal infections. Unfortunately, there is a lack of pharmacoeconomic studies addressing the costs
associated with the treatment and prevention of fungal infections. Future large-scale clinical studies should include pharmacoeconomic
analyses and end points that encompass all costs associated with antifungal drug use, not solely drug acquisition costs. 相似文献
16.
Nathan P. Wiederhold 《Current fungal infection reports》2009,3(2):77-85
Invasive fungal infections remain significant clinical challenges and are associated with high morbidity and mortality in
immunocompromised patients. Despite the availability of new antifungal agents, response rates against many of these infections
remain suboptimal. In addition, many of the clinically available agents have limited oral bioavailability, are associated
with adverse effects due to similarities between fungal and mammalian cells, or have significant drug-drug interactions. For
these reasons, there is great interest in developing new antifungal drugs, including those with novel mechanisms of action.
This article reviews the pharmacology, in vitro activity, and in vivo effectiveness of new antifungal agents, including members
of new classes with novel mechanisms of action and at various stages of preclinical and clinical development. These agents
include the triazole isavuconazole, the echinocandin aminocandin, the histone deacetylase inhibitor MGCD290, and the sordarin
derivative FR290581. 相似文献
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18.
Lin Liu Tong Jiang Jia Zhou Yikun Mei Jinyang Li Jingcong Tan Luqi Wei Jingquan Li Yibing Peng Changbin Chen Ning-Ning Liu Hui Wang 《Microbial biotechnology》2022,15(2):482-498
Fungal infections have emerged as a major global threat to human health because of the increasing incidence and mortality rates every year. The emergence of drug resistance and limited arsenal of antifungal agents further aggravates the current situation resulting in a growing challenge in medical mycology. Here, we identified that ponatinib, an FDA-approved antitumour drug, significantly enhanced the activity of the azole fluconazole, the most widely used antifungal drug. Further detailed investigation of ponatinib revealed that its combination with fluconazole displayed broad-spectrum synergistic interactions against a variety of human fungal pathogens such as Candida albicans, Saccharomyces cerevisiae and Cryptococcus neoformans. Mechanistic insights into the mode of action unravelled that ponatinib reduced the efflux of fluconazole via Pdr5 and suppressed the expression of the proton pump, Pma1. Taken together, our study identifies ponatinib as a novel antifungal that enhances drug activity of fluconazole against diverse fungal pathogens. 相似文献
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20.
Microbial attachment onto biomedical devices and implants leads to biofilm formation and infection; such biofilms can be bacterial, fungal, or mixed. In the past 15 years, there has been an increasing research effort into antimicrobial surfaces but the great majority of these publications present research on bacteria, with some reports also testing resistance to fungi. Very few studies have focused exclusively on antifungal surfaces. However, with increasing recognition of the importance of fungal infections to human health, particularly related to infections at biomaterials, it would seem that the interest in antifungal surfaces is disproportionately low. In studies of both bacteria and fungi, fungi tend to be the minor focus with hypothesized antibacterial mechanisms of action often generalized to also explain the antifungal effect. Yet bacteria and fungi represent two Distinct biological Domains and possess substantially different cellular physiology and structure. Thus it is questionable whether these generalizations are valid. Here we review the scientific literature focusing on surface coatings prepared with antifungal agents covalently attached to the biomaterial surface. We present a critical analysis of generalizations and their evidence. This review should be of interest to researchers of “antimicrobial” surfaces by addressing specific issues that are key to designing and understanding antifungal biomaterials surfaces and their putative mechanisms of action. 相似文献