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1.
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
2.
Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis. 相似文献
3.
Given the substantial morbidity and mortality related to invasive fungal infections, treatment with a combination of antifungal
agents is often considered. A growing body of literature from in vitro studies, animal models, and clinical experience provides
data evaluating this approach. This review describes combination antifungal strategies for the management of cryptococcal
meningitis, invasive candidiasis, invasive aspergillosis, and rare mold infections. The potential effects that sequencing
and timing have on the efficacy of such approaches are discussed, with a focus on recent clinical data in this arena. 相似文献
4.
Nathan P. Wiederhold 《Current fungal infection reports》2010,4(2):70-77
In vitro and in vivo studies of available and investigational antifungals have broadened our understanding of the pharmacodynamics
of these agents as well as the pharmacokinetic/pharmacodynamic characteristics that are associated with efficacy. These data
are increasingly being used as surrogate means to answer questions about dosing and administration of antimicrobial agents
in order to improve outcomes in patients with invasive fungal infections, as these questions are difficult to answer in clinical
trials. The objective of this article is to review the pharmacodynamic activity of widely used classes of antifungal agents,
including the azoles, amphotericin B, and the echinocandins, discuss the pharmacokinetic/pharmacodynamic parameters associated
with efficacy of these agents in preclinical studies, and describe how this information is being translated into the clinical
arena to optimize patient outcomes. 相似文献
5.
The incidence of invasive fungal infections continues to increase, especially in patients with immune dysfunction. Fungal
infections are often difficult to treat, requiring therapy for weeks or months to eradicate infection. Although fungal infections
of the central nervous system, eye, and bones occur less frequently than infections at other sites, it is necessary to assess
the utility of the currently available antifungal agents in treating these infections. Unfortunately, information regarding
drug distribution to these sites is often scarce and limited to a few animal studies or case reports. This review summarizes
information about commonly used antifungal agents and their penetration into the central nervous system, eye, and bone. 相似文献
6.
《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
7.
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
8.
Adjusting the dose of antifungal agents for renal and hepatic impairment can be challenging given that clinicians must rely
on limited pharmacokinetic data to derive specific regimens. These pharmacokinetic studies are typically performed in a small
number of patients without invasive fungal infection, and results are not often reported in concert with accepted pharmacodynamic
indices. This article aims to review pertinent pharmacokinetic studies of antifungal drugs in patients with renal or hepatic
dysfunction. The impact of novel continuous renal replacement therapy techniques on the pharmacokinetic disposition of antifungal
agents will also be described where data are available. Subsequently, this review provides recommendations for antifungal
drug dosing in patients with kidney or liver dysfunction after accounting for established or emerging pharmacokinetic-pharmacodynamic
relationships as they relate to antifungal drug efficacy in vivo. 相似文献
9.
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
10.
Victoria M. Stevens Scott W. Mueller Paul M. Reynolds Robert MacLaren Tyree H. Kiser 《Current fungal infection reports》2020,14(1):50-62
This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable. Animal studies have helped identify area under the concentration curve to minimum inhibitory concentration ratio targets for new drugs and formulations such as isavuconazole and delayed-release posaconazole that have translated to successful outcomes in humans. Models have also been influential in the identification of possible combination therapies for the treatment of aspergillosis, such as voriconazole and echinocandins. However, challenges are endured with animal models when it comes to replicating the pharmacokinetics of humans which has been exemplified with the newest itraconazole formulation. Additionally, animal models have displayed a survival benefit with the use of iron chelators and amphotericin for mucormycosis which was not demonstrated in humans. Animal models have been a staple in the development and optimization of antifungal agents. They afford the ability to investigate uncommon diseases, such as invasive fungal infections, that would otherwise take years and many resources to complete. Although there are many benefits of animal models, there are also shortcomings. This is why the reliability of extrapolating data from animal models to humans is often scrutinized. 相似文献
11.
Invasive fungal infections have become a major cause of mortality in immunocompromised individuals. Despite the current availability of number of highly active antifungal agents, overall mortality remains around 40%. Importantly, it is clear that a failure to restore host immunity leads to worse outcomes. These observations provide clear rationale for the development of novel immunotherapies to improve outcomes in immunocompromised individuals with invasive fungal infections. In this article we summarise the key advances that have been made in the field of immunotherapy for fungal infections in recent years, with a particular focus on clinical studies of interferon-γ therapy, adoptive T cell therapy, and gene therapy for chronic granulomatous disorder. In addition a number of pre-clinical approaches are reviewed. 相似文献
12.
Systemic fungal infections are increasing in prevalence, especially in immunocompromised patients and post-surgical patients. The rise in systemic fungal infections has resulted in increased utilization of antifungal agents which, in turn, has contributed to escalating resistance rates as seen by the increasing number of fungal pathogens added to the Centers for Disease Control and Prevention Antimicrobial Resistance Threats Report in 2019. Unfortunately, there are few novel antifungal agents coming to market to combat these ever-increasing resistance rates. In this review, we cover the current climate of antifungal agents and explore agents coming through the pipeline and potentially to market. We also discuss the indicated uses for empiric and targeted antifungal therapies as well as the need to include antifungal agents as a part of antimicrobial stewardship programs that focus heavily on antibacterial agents. 相似文献
13.
Dermatophytoses are common superficial fungal infections affecting both humans and animals. They are provoked by filamentous fungi called dermatophytes specialized in the degradation of keratinized structures, which allows them to induce skin, hair and nail infections. Despite their high incidence, little investigation has been performed for the understanding of these infections compared to fungal opportunistic infections and most of the studies were based on in vitro experiments. The development of animal models for dermatophyte research is required to evaluate new treatments against dermatophytoses or to increase knowledge about fungal pathogenicity factors or host immune response mechanisms. The guinea pig has been the most often used animal model to evaluate efficacy of antifungal compounds against dermatophytes, while mouse models were preferred to study the immune response generated during the disease. Here, we review the relevant animal models that were developed for dermatophyte research and we discuss the advantages and disadvantages of the selected species, especially guinea pig and mouse. 相似文献
14.
Invasive fungal infections are major causes of mortality in immunocompromised patients. Despite improved outcomes with new
antifungals, there remains a pressing need to further improve outcomes, especially with invasive aspergillosis and other invasive
mold infections. Combination antifungal therapy is an attractive option that offers the prospect for improved efficacy, decreased
toxicity, reduced likelihood for the emergence of resistance, and shorter courses of therapy. The current available evidence
regarding the role of combination antifungal therapy for invasive fungal infections is discussed in this article, including
data from in vitro studies, animal models, and human clinical trials to try to clarify this important issue. Randomized, prospective
clinical trials are urgently needed, especially for invasive aspergillosis. 相似文献
15.
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
16.
Douglas N. Fish 《Current fungal infection reports》2011,5(2):75-82
Appropriate dosing of antifungal drugs is crucial to achieving favorable outcomes in patients with invasive fungal infections.
The use of various types of renal replacement therapy (RRT) in patients with severe acute or chronic renal insufficiency adds
another level of complexity to the already challenging use of these drugs. The medical literature provides only a limited
number of studies specifically addressing the use of antifungal agents in patients receiving RRT, and there are a number of
inherent difficulties in interpreting and applying these studies of drug dosing during RRT to individual patients. This article
briefly reviews recent studies examining the dosing of antifungal agents during RRT, and also briefly reviews device-related
and drug-related factors that determine the removal of drugs during RRT. Finally, this article summarizes current recommendations
for dosing of antifungal agents in patients receiving RRT and highlights areas for future study. 相似文献
17.
Steinbach WJ Reedy JL Cramer RA Perfect JR Heitman J 《Nature reviews. Microbiology》2007,5(6):418-430
The number of immunocompromised patients with invasive fungal infections continues to increase and new antifungal therapies are not keeping pace with the growing incidence of these infections and their associated mortality. Calcineurin inhibition is currently used to exert effective immunosuppression following organ transplantation and in treating various other conditions. However, the calcineurin pathway is also intricately involved in the growth and pathogenesis of the three major fungal pathogens of humans, Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus, and the exploitation of fungal calcineurin pathways holds great promise for the future development of novel antifungal agents. This Review summarizes our current understanding of calcineurin biology in these fungal species, and its exciting potential role in treating invasive fungal infections. 相似文献
18.
M F Tuite 《Trends in biotechnology》1992,10(7):235-239
With the increasing prevalence of life-threatening systemic fungal infections in the human population, there is a need to develop new, more-effective antifungal agents. This, in turn, will depend upon the identification and exploitation of new antifungal targets--aspects of fungal cytology, metabolism and gene expression which are important for fungal pathogenesis, but which have no mammalian host counterpart. Such new targets have been identified through a combination of classical genetic, cytological and biochemical studies and are reviewed here, as is the potential for applying recombinant DNA techniques as a means of confirming the role of the identified gene products in pathogenesis. 相似文献
19.
Antifungal agents: mechanisms of action 总被引:16,自引:0,他引:16
Clinical needs for novel antifungal agents have altered steadily with the rise and fall of AIDS-related mycoses, and the change in spectrum of fatal disseminated fungal infections that has accompanied changes in therapeutic immunosuppressive therapies. The search for new molecular targets for antifungals has generated considerable research using modern genomic approaches, so far without generating new agents for clinical use. Meanwhile, six new antifungal agents have just reached, or are approaching, the clinic. Three are new triazoles, with extremely broad antifungal spectra, and three are echinocandins, which inhibit synthesis of fungal cell wall polysaccharides--a new mode of action. In addition, the sordarins represent a novel class of agents that inhibit fungal protein synthesis. This review describes the targets and mechanisms of action of all classes of antifungal agents in clinical use or with clinical potential. 相似文献
20.
Steven Trifilio 《Current fungal infection reports》2011,5(2):92-102
The prevention and treatment of invasive fungal infections can be compromised by antifungal agents that display unpredictable
pharmacokinetics and significant drug interactions and which demonstrate a strong relationship between drug exposure and efficacy
and toxicity. Clinical studies have shown that maintaining antifungal drug levels within a targeted range decreases the risk
for treatment failure and drug toxicity and thus have established a role for therapeutic drug monitoring with the use of various
agents. Evidence from experimental and clinical studies supporting the role of therapeutic drug monitoring and practical applications
for attaining targeted levels are reviewed. 相似文献