Systemic antifungal drugs

Mayo Clinic proceedings, 2011

The introduction of new antifungal agents (eg, echinocandins, second-generation triazoles) in the past decade has transformed the management of invasive mycoses to the point that drug toxicity is no longer the major limiting factor in treatment. Yet, many of these newer antifungal agents have important limitations in their spectrum of activity, pharmacokinetics, and unique predisposition for pharmacokinetic drug-drug interactions and unusual toxicities associated with long-term use. This article reviews key pharmacological aspects of systemic antifungal agents as well as evolving strategies, such as pharmacokinetic-pharmacodynamic optimization and therapeutic drug monitoring, to improve the safety and efficacy of systemic antifungal therapy.

Journal of the American Academy of Dermatology, 1994

The recent introductionof a newgenerationof antifungal drugs promisesto alter significantly therapy for both systemicand superficial mycoses, in particular, onychomycosis. This article presents an in-depth review of the azoles(the triazoles itraconazole and fluconazole), the allylamines (naftifineand terbinafine), and the morpholinederivative amorolfine. (J AMACAD DERMATOL 1994;30:911-33.) Learning objective: At the conclusion of this learning activity, participants should be able to discussselected new approachesto antifungal drug therapy for superficial and systemic mycoses, especially onychomycosis.

Pediatria i Medycyna Rodzinna, 2019

The paper addresses the issue of fungal infections in the context of growing resistance to currently available antifungal agents and the development of new antimycotics. Fungal pathogens belonging to the genuses Candida, Aspergillus, Pneumocystis and Cryptococcus account for about 90% of all fungal infections. Candida albicans infections are a global clinical problem, and systemic candidiasis is considered one of the most severe fungal infections, with mortality rates of about 40% despite treatment. Currently, there are five classes of antimycotics available, of which only three (azoles, echinocandins and polyenes) are used for systemic infections. The limited variety of available therapies as well as their overuse in both therapy and prevention have contributed to the growing resistance among fungal pathogens. Many mechanisms of resistance to antimycotics have been identified. These include in particular: mutations in genes encoding target proteins, increase or decrease in target protein, protein pump activity, biofilm formation or activation of stress response. The growing incidence of fungal infections and the difficulty of their treatment have forced the search for alternative therapeutic agents with new mechanisms of action. Due to the eukaryotic nature of fungal cells, recent trends in literature imply that novel agents should specifically target virulence factors or stress response of the pathogen.

Clinical Infectious Diseases, 2006

Traditionally, many invasive fungal infections were associated with a poor prognosis, because effective therapeutic options were limited. The recent development of new antifungal agents has significantly contributed to the successful treatment of fungal diseases. These drugs offer novel mechanisms of action and expanded spectrums of activity over traditional treatment options. However, with these new agents comes the need for increased awareness of the potential interactions and toxicities associated with these drugs. Therefore, an understanding of the pharmacokinetic and pharmacodynamic properties of the classes of antifungal compounds is vital for the effective management of invasive fungal infections. This review provides a summary of the pharmacologic principles involved in treatment of fungal diseases.

Journal of Basic Research in Medical Sciences, 2018

Antifungals have always been considered as one of the astonishing discoveries of the 20th century. This is correct, but the real marvel is the development of antifungal resistance in hospitals, communities, and the environment concomitant with their use. Fungal infections have emerged as an important clinical threat, with significant associated morbidity and mortality. This study is designed to provide a comprehensive view of antifungal agents and related agents. Information was based on the expertise of some literatures. Over the past decades, the incidence and diversity of fungal infection has grown in association with an increasing number of immunocompromised patients. An understanding of the pharmacokinetic and pharmacodynamics properties of the classes of antifungal compounds is vital for the effective management of invasive fungal infections. This review provides a summary of the pharmacologic principles involved in treatment of fungal diseases. 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 change in therapeutic immunosuppressive therapies.

Journal of Antimicrobial Chemotherapy, 2005

For many years, amphotericin B and flucytosine have been the only antifungal agents for invasive fungal infections. Amphotericin B was the standard of care for most of these infections. However, its use was often associated with low efficacy and poor tolerance. 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, caspofungin and micafungin have arrived on the market. Other agents are expected to be licensed shortly (anidulafungin, posaconazole). These various antifungal agents differ in their spectrum, pharmacokinetic profile, route of administration, efficacy in clinical trials, safety profile, drug-drug interactions and, importantly, their cost. There is no longer a unique standard agent for all or nearly all invasive fungal infections but a real choice among several agents. The characteristics of these new agents are reviewed to help clinicians in their decision to select an antifungal agent for their patients.

2000

Invasive fungal infections have emerged as im- portant causes of morbidity and mortality in im- munocompromised patients. In response to this challenge, the field of antifungal chemotherapy has considerably expanded. Fluconazole and itra- conazole, introduced in the late 1980s, were the first durably useful alternatives to amphotericin B deoxycholate. The clinical development of the lipid formulations of amphotericin B, and,

Journal of Hospital Infection, 2003

Despite significant advances in the management of immunosuppressed patients, invasive fungal infections remain an important life-threatening complication. In the last decade several new antifungal agents, including compounds in pre-existing classes (new generation of triazoles, polyenes in lipid formulations) and novel classes of antifungals with a unique mechanism of action (echinocandins), have been introduced in clinical practice. Ongoing and future studies will determine their exact role in the management of different mycoses. The acceleration of antifungal drug discovery offers promise for the management of these difficult to treat opportunistic infections.

International Journal of Biomedical and Advance Research, 2011

The number of fungi causing systemic disease is growing and the number of systemic diseases caused by fungi is increasing. The currently available antifungal agents for the treatment of systemic mycoses include polyene antibiotics (Amphotericin B), fluoropyrimidine (Flu cytosine), and Nystatin andazole group of drugs (Ketoconazole, Fluconazole, and Itraconazole). Novel drug delivery systems for antifungal therapy, based on the type of formulation are classified as Liposomes Nanocochleates, Nanospheres, Carbon Nanotubes, Doubled layered Mucoadhesive Tablets, Mucoadhesive Thermo Sensitive Pronged release gels, and Parenteral Micro emulsions. Amphotericin B is the only fungicidal agent available and is the 'goldstandard' for the treatment of most of the systemic mycoses. The three currently available lipid formulations are Amphotericin B Lipid Complex (ABLC), Amphotericin B Colloidal Dispersion (ABCD) and Liposomal Amphotericin B (L-AmB). Nystatin and ketoconazole are also commercially available as liposomes. Novel Drug delivery systems for antifungal therapy, aiming at reducing the side effects and maximizing the antifungal activity have added a new dimension to the treatment of fungal infections. Without fungi we would not have bread, beer, wine or antibiotics, but more importantly without the nutrient recycling and plant nutrition provided by fungi-we probably could not survive at all.

British Journal of Haematology, 2004

The availability of new antifungal agents with unique mechanisms of action and improved tolerability has widened the possibilities for the use of combination antifungal therapy for difficult-to-treat opportunistic mycoses. However, the use of this therapy is largely governed by empiricism, especially in patients with invasive mould infections, for whom there is a tremendous need to improve outcomes. Because of the difficulties associated with the design and conduct of clinical trials of combination antifungal therapy for opportunistic mycoses, the majority of the studies evaluating antifungal combinations are still performed in the laboratory or using animal models of infection. However, the methods used to assess combined antifungal effects in vitro and in animals are poorly standardized, and there is little evidence that data generated from these studies can be translated in treating human mycotic infections. Despite the empiricism of combination antifungal therapy, certain principles help guide the use and study of these regimens.