Clinical Use of Cytokines during Fungal Infections

2015 ◽  
pp. 90-97 ◽  
Author(s):  
Emmanuel Roilides ◽  
Thomas J. Walsh ◽  
Philip A. Pizzo
Keyword(s):  
Fungal Infections ◽  
Clinical Use

Antifúngicos poliénicos. Mecanismo de acción y aplicaciones

2020 ◽  
Vol 63 (2) ◽  
pp. 7-17
Author(s):  
Evelyn Rivera-Toledo ◽  
Alan Uriel Jiménez-Delgadillo ◽  
Patricia Manzano-Gayosso
Keyword(s):  
Antifungal Activity ◽  
Key Words ◽  
Secondary Metabolism ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Variable Number ◽  
Therapeutic Failure ◽  
Morbidity And Mortality ◽  
Clinical Use

The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model. Key words: Amphotericin B; antifungal polyenes; ergosterol

scholarly journals Pharmacodynamics of the Orotomides against Aspergillus fumigatus : New Opportunities for Treatment of Multidrug-Resistant Fungal Disease

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
William W. Hope ◽  
Laura McEntee ◽  
Joanne Livermore ◽  
Sarah Whalley ◽  
Adam Johnson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Mechanism Of Action ◽  
Drug Exposure ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Clinical Use ◽  
Drug Concentrations ◽  
Phase Ii And Iii

ABSTRACT F901318 is an antifungal agent with a novel mechanism of action and potent activity against Aspergillus spp. An understanding of the pharmacodynamics (PD) of F901318 is required for selection of effective regimens for study in phase II and III clinical trials. Neutropenic murine and rabbit models of invasive pulmonary aspergillosis were used. The primary PD endpoint was serum galactomannan. The relationships between drug exposure and the impacts of dose fractionation on galactomannan, survival, and histopathology were determined. The results were benchmarked against a clinically relevant exposure of posaconazole. In the murine model, administration of a total daily dose of 24 mg/kg of body weight produced consistently better responses with increasingly fractionated regimens. The ratio of the minimum total plasma concentration/MIC ( C min /MIC) was the PD index that best linked drug exposure with observed effect. An average C min (mg/liter) and C min /MIC of 0.3 and 9.1, respectively, resulted in antifungal effects equivalent to the effect of posaconazole at the upper boundary of its expected human exposures. This pattern was confirmed in a rabbit model, where C min and C min /MIC targets of 0.1 and 3.3, respectively, produced effects previously reported for expected human exposures of isavuconazole. These targets were independent of triazole susceptibility. The pattern of maximal effect evident with these drug exposure targets was also apparent when survival and histopathological clearance were used as study endpoints. F901318 exhibits time-dependent antifungal activity. The PD targets can now be used to select regimens for phase II and III clinical trials. IMPORTANCE Invasive fungal infections are common and often lethal. There are relatively few antifungal agents licensed for clinical use. Antifungal drug toxicity and the emergence of drug resistance make the treatment of these infections very challenging. F901318 is the first in a new class of antifungal agents called the orotomides. This class has a novel mechanism of action that involves the inhibition of the fungal enzyme dihydroorotate dehydrogenase. F901318 is being developed for clinical use. A deep understanding of the relationship between dosages, drug concentrations in the body, and the antifungal effect is fundamental to the identification of the regimens to administer to patients with invasive fungal infections. This study provides the necessary information to ensure that the right dose of F901318 is used the first time. Such an approach considerably reduces the risks in drug development programs and ensures that patients with few therapeutic options can receive potentially life-saving antifungal therapy at the earliest opportunity.

Clinical Use and Tolerability of Voriconazole in the Treatment of Fungal Infections in Critically Ill Patients

2005 ◽  
Vol 17 (4) ◽  
pp. 417-427 ◽  
Author(s):  
F. Álvarez-lerma ◽  
J.M. Nicolás-Arfelis ◽  
J.C. Rodríguez-Borregán ◽  
J. Díaz-Regañón ◽  
M. Sa-Borges ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Fungal Infections ◽  
Clinical Use

scholarly journals A Review of Clinical Experience with Newer Antifungals in Children

2008 ◽  
Vol 13 (3) ◽  
pp. 124-140
Author(s):  
Renee M. Fallon ◽  
Jennifer E. Girotto
Keyword(s):  
Children And Adolescents ◽  
21St Century ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Pediatric Population ◽  
Pharmacokinetic Data ◽  
Clinical Use ◽  
Clinical Experiences ◽  
Key Concepts ◽  
Pediatric Pharmacology

Fungal infections are a significant cause of morbidity and mortality in immunocompromised children. Since the beginning of the 21st century, many new antifungals including the echinocandins (i.e., caspofungin, micafungin, anidulafungin) and the newer generation triazoles (i.e., voriconazole and posaconazole) have received Food and Drug Administration approval. Unfortunately, despite making great strides in the adult arena, these agents are not currently approved in the pediatric population. However, pharmacokinetic data and clinical experiences with these agents in infants, children, and adolescents are mounting. As such, this review will discuss key concepts in pediatric pharmacology and clinical use of these newer antifungal agents.

scholarly journals Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties.

1995 ◽  
Vol 6 (2) ◽  
pp. 154-164 ◽  
Author(s):  
B P Sawaya ◽  
J P Briggs ◽  
J Schnermann
Keyword(s):  
Amphotericin B ◽  
Cell Function ◽  
Fungal Infections ◽  
Cell Membrane Permeability ◽  
Membrane Properties ◽  
Clinical Use ◽  
Salt Loading ◽  
Tubular Transport ◽  
Recurrent Ischemia ◽  
Care Support

Amphotericin B (AmB) has been in clinical use for more than 30 yr but has remained the most effective drug for treatment of serious fungal infections. Its use has increased in recent years, as the result of increases in aggressive intensive care support and increased numbers of immunocompromised patients. Nephrotoxic manifestations are common, and this is the major factor limiting the clinical use of the drug. A number of recent studies have contributed to a better understanding of the mechanism by which AmB exerts its nephrotoxic effect. AmB alters cell membrane permeability and probably as a consequence alters tubular and vascular smooth muscle cell function, leading to various tubular transport defects and vasoconstriction. Decreased RBF appears to play a major role in AmB-induced reduction GFR, and recurrent ischemia may be the basis of permanent structural nephrotoxic effects. Salt loading is the only measure proven by controlled prospective study to ameliorate AmB nephrotoxicity in humans. Liposomal AmB and the formulation of an emulsion of AmB in lipid may provide a protective effect based on altering the affinity of AmB for mammalian cell membranes, while preserving high efficacy against fungal cells. However, further studies are needed to evaluate the efficacy and safety of these new AmB formulations.

scholarly journals Amphotericin B and Other Polyenes—Discovery, Clinical Use, Mode of Action and Drug Resistance

2020 ◽  
Vol 6 (4) ◽  
pp. 321
Author(s):  
Hans Carolus ◽  
Siebe Pierson ◽  
Katrien Lagrou ◽  
Patrick Van Dijck
Keyword(s):  
Drug Resistance ◽  
Amphotericin B ◽  
Mode Of Action ◽  
Fungal Infections ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Clinical Use ◽  
Candida Auris ◽  
Resistance Development ◽  
Resistant Species

Although polyenes were the first broad spectrum antifungal drugs on the market, after 70 years they are still the gold standard to treat a variety of fungal infections. Polyenes such as amphotericin B have a controversial image. They are the antifungal drug class with the broadest spectrum, resistance development is still relatively rare and fungicidal properties are extensive. Yet, they come with a significant host toxicity that limits their use. Relatively recently, the mode of action of polyenes has been revised, new mechanisms of drug resistance were discovered and emergent polyene resistant species such as Candida auris entered the picture. This review provides a short description of the history and clinical use of polyenes, and focusses on the ongoing debate concerning their mode of action, the diversity of resistance mechanisms discovered to date and the most recent trends in polyene resistance development.

scholarly journals Application of the 1,3-β-d-Glucan (Fungitell) Assay in the Diagnosis of Invasive Fungal Infections

2016 ◽  
Vol 140 (2) ◽  
pp. 181-185 ◽  
Author(s):  
Tuan Tran ◽  
Stacy G. Beal
Keyword(s):  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Cape Cod ◽  
Clinical Settings ◽  
Evidence Based ◽  
Clinical Use ◽  
Noninvasive Method ◽  
Cell Wall Component ◽  
A Cell ◽  
Detection And Diagnosis

With the high mortality rate associated with invasive fungal infections, methods for timely detection and diagnosis are necessary for appropriate and effective treatment. Testing for 1,3-β-d-glucan, a cell wall component of many medically important fungi, can be a useful adjunct in diagnosing such infections. The Fungitell assay (Associates of Cape Cod, East Falmouth, Massachusetts) is a US Food and Drug Administration–approved laboratory test that quantitatively measures 1,3-β-d-glucan levels and is widely available for clinical use as a relatively noninvasive method to aid in detecting the presence of invasive fungal infections. Numerous studies have evaluated its performance in clinical settings, and results have, overall, been favorable. It is not without its drawbacks, however, and the test must be interpreted and applied with care. Ordering practices are also widely variable among clinicians, and official guidelines have not been readily available. We present the details of this test and aim to propose evidence-based guidance for its use.

Assessing Functional Language in School-Aged Children Using Language Sample Analysis

2020 ◽  
Vol 5 (3) ◽  
pp. 622-636
Author(s):  
John Heilmann ◽  
Alexander Tucci ◽  
Elena Plante ◽  
Jon F. Miller
Keyword(s):  
Computer Hardware ◽  
School Age Children ◽  
Functional Language ◽  
School Age ◽  
Clinical Use ◽  
Sample Analysis ◽  
Validity And Reliability ◽  
Language Sample Analysis ◽  
Accuracy And Repeatability ◽  
Language Sample

Purpose The goal of this clinical focus article is to illustrate how speech-language pathologists can document the functional language of school-age children using language sample analysis (LSA). Advances in computer hardware and software are detailed making LSA more accessible for clinical use. Method This clinical focus article illustrates how documenting school-age student's communicative functioning is central to comprehensive assessment and how using LSA can meet multiple needs within this assessment. LSA can document students' meaningful participation in their daily life through assessment of their language used during everyday tasks. The many advances in computerized LSA are detailed with a primary focus on the Systematic Analysis of Language Transcripts (Miller & Iglesias, 2019). The LSA process is reviewed detailing the steps necessary for computers to calculate word, morpheme, utterance, and discourse features of functional language. Conclusion These advances in computer technology and software development have made LSA clinically feasible through standardized elicitation and transcription methods that improve accuracy and repeatability. In addition to improved accuracy, validity, and reliability of LSA, databases of typical speakers to document status and automated report writing more than justify the time required. Software now provides many innovations that make LSA simpler and more accessible for clinical use. Supplemental Material https://doi.org/10.23641/asha.12456719

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