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Drugs 2009Drug classes for the treatment of invasive fungal infections include the polyenes, the triazoles and the echinocandins. Older agents such as the commonly used... (Review)
Review
Drug classes for the treatment of invasive fungal infections include the polyenes, the triazoles and the echinocandins. Older agents such as the commonly used amphotericin B have a number of limitations, including toxicity and requirements for monitoring during treatment. These limitations led to the development of a number of new formulations of the agent, with the aim of reducing toxicity while maintaining or improving efficacy. Regarding other drug classes, some of the newer agents, such as the echinocandins, have more favourable pharmacokinetic/pharmacodynamic (PK/PD) profiles, with less toxicity and no need for monitoring. The newest echinocandin, anidulafungin, offers significant promise for antifungal infections, and has a number of favourable features, including a lack of known drug interactions and no need for dosage adjustment for any degree of renal or hepatic failure. From a pharmacological point of view, knowledge of both PK and PD characteristics of antifungal drugs is mandatory for evaluating the role of the different agents in the clinical setting. Overall, in the search for safer and more efficacious antifungal agents, PK/PD investigations have been valuable for defining optimal antifungal dosing regimens and developing in vitro susceptibility breakpoints. This article reviews the PK/PD properties of the polyenes, the triazoles and the echinocandins, with a focus on anidulafungin.
Topics: Anidulafungin; Animals; Antifungal Agents; Echinocandins; Fungi; Humans; Polyenes; Triazoles
PubMed: 19877739
DOI: 10.2165/11315550-000000000-00000 -
European Journal of Medical Research Apr 2011Echinocandins represent the newest class of antifungal agents. Currently, three echinocandins, anidulafungin, caspofungin and micafungin are licensed for clinical use in... (Review)
Review
Echinocandins represent the newest class of antifungal agents. Currently, three echinocandins, anidulafungin, caspofungin and micafungin are licensed for clinical use in various indications. They act as inhibitors of β-(1,3)-glucan synthesis in the fungal cell wall and have a favorable pharmacological profile. They have a broad spectrum of activity against all Candida species. Higher MIC's have been observed against C. parapsilosis and C. guilliermondii. Data from clinical trials for invasive Candida infections / candidaemia suggest that the clinical outcome of patients treated with either drug may be very similar. A comparison has been done between caspofungin and micafungin but for anidulafungin a comparative trial with another echinocandin is still lacking. All three drugs are highly effective if not superior to treatment with either fluconazole or Amphotericin B, particularly in well-defined clinical settings such as invasive Candida infections, Candida oesophagitis and candidaemia. Differences between the three echinocandins with regard to the route of metabolism, requirement for a loading dose, dose adjustment in patients with moderate to severe hepatic disease and different dosing schedules for different types of Candida infections have to be considered. Relevant drug-drug interactions of Caspofungin and Micafungin are minimal. Anidulafungin has no significant drug interactions at all. However, echinocandins are available only for intravenous use. All three agents have an excellent safety profile.
Topics: Anidulafungin; Antifungal Agents; Biofilms; Candidiasis, Invasive; Caspofungin; Drug Interactions; Drug Resistance, Fungal; Echinocandins; Humans; Lipopeptides; Micafungin; Molecular Structure
PubMed: 21486730
DOI: 10.1186/2047-783x-16-4-159 -
Recent Patents on Anti-infective Drug... Apr 2012Fungal infections are becoming an increasing menace in the hospital care setting. Among them, non-albicans Candida species have gained significant attention. Especially... (Review)
Review
Fungal infections are becoming an increasing menace in the hospital care setting. Among them, non-albicans Candida species have gained significant attention. Especially in the ICU setting, therapeutic options are limited in many cases by the side-effects of conventional antifungal therapy. Echinocandins are a relatively new class of antifungal agents that promise good effectiveness against Candida and Aspergillus species. Due to their underlying mechanisms of action, they yield good tolerability and few limitations of usage. In the current manuscript we describe the patents of two recently approved echinocandins, micafungin (US approved 2005) and anidulafungin (2006) and provide an overview of the mechanisms, clinical effectiveness and safety of antifungal therapy with these agents.
Topics: Anidulafungin; Animals; Antifungal Agents; Aspergillus; Candida; Echinocandins; Humans; Lipopeptides; Micafungin; Patents as Topic
PubMed: 22044354
DOI: 10.2174/157489112799829747 -
Journal of Obstetrics and Gynaecology :... May 2021
Topics: Adult; Anidulafungin; Antifungal Agents; Azoles; Candida albicans; Candidiasis, Vulvovaginal; Drug Resistance, Fungal; Female; Fluconazole; Humans; Microbial Sensitivity Tests; Turkey
PubMed: 32312119
DOI: 10.1080/01443615.2020.1732893 -
Clinical Pharmacokinetics Oct 2016Bodyweight has been shown to influence anidulafungin exposure, but data from obese patients are lacking. We determined anidulafungin pharmacokinetics (100-mg single...
Bodyweight has been shown to influence anidulafungin exposure, but data from obese patients are lacking. We determined anidulafungin pharmacokinetics (100-mg single dose) in eight morbidly obese subjects (body mass index >40 kg/m(2)). Anidulafungin exposure was on average 32.5 % lower compared with the general patient population, suggesting dose increases may be required in this population.
Topics: Adult; Aged; Anidulafungin; Antifungal Agents; Area Under Curve; Body Mass Index; Echinocandins; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Obesity, Morbid
PubMed: 27142114
DOI: 10.1007/s40262-016-0401-8 -
Antimicrobial Agents and Chemotherapy Apr 2018Anidulafungin concentrations were quantified with high-pressure liquid chromatography (HPLC) and UV detection of the ascites fluid and pleural effusion of 10 adult...
Anidulafungin concentrations were quantified with high-pressure liquid chromatography (HPLC) and UV detection of the ascites fluid and pleural effusion of 10 adult critically ill patients. Samples were collected from ascites fluid and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulafungin levels in ascites fluid (0.12 to 0.99 μg/ml) and in pleural effusion (0.32 to 2.02 μg/ml) were below the simultaneous levels in plasma (1.04 to 7.70 and 2.48 to 13.36 μg/ml, respectively) and below the MIC values for several pathogenic strains.
Topics: Adult; Aged; Aged, 80 and over; Anidulafungin; Antifungal Agents; Ascites; Candida; Chromatography, High Pressure Liquid; Critical Illness; Echinocandins; Female; Humans; Male; Middle Aged; Pleural Effusion
PubMed: 29439960
DOI: 10.1128/AAC.02326-17 -
Revista Iberoamericana de Micologia Jun 2008Currently, no standardized method to study the in vitro activity of antifungal agents on biofilms is available, thus, the comparison among different authors is... (Review)
Review
Currently, no standardized method to study the in vitro activity of antifungal agents on biofilms is available, thus, the comparison among different authors is difficult. The studies discussed in this review use the XTT reduction to measure the activity of antifungals on biofilms of 24 h of maturation. To date, biofilm anidulafungin MICs of 47 isolates of Candida spp. (25 Candida albicans, 16 Candida tropicalis, 5 Candida dubliniensis and 1 Candida parapsilosis) have been published. The geometric mean MIC of anidulafungin on biofilms of Candida spp. is of 1.18 microg/ml. Against isolates of species with great capacity of biofilm formation, the geometric mean MIC is 0.325 (C. albicans), 2 (C. parapsilosis) and 0.5 microg/ml (C. dubliniensis). No echinocandin has activity on C. tropicalis biofilms. In addition, anidulafungin can be used for lock therapy of catheters since it is the echinocandin with the least in vitro paradoxical effect.
Topics: Anidulafungin; Antifungal Agents; Biofilms; Candida; Echinocandins
PubMed: 18473507
DOI: 10.1016/s1130-1406(08)70030-5 -
The New England Journal of Medicine Jun 2007Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority trial of treatment for invasive candidiasis.
METHODS
Adults with invasive candidiasis were randomly assigned to receive either intravenous anidulafungin or intravenous fluconazole. All patients could receive oral fluconazole after 10 days of intravenous therapy. The primary efficacy analysis assessed the global response (clinical and microbiologic) at the end of intravenous therapy in patients who had a positive baseline culture. Efficacy was also assessed at other time points.
RESULTS
Eighty-nine percent of the 245 patients in the primary analysis had candidemia only. Candida albicans was isolated in 62% of the 245 patients. In vitro fluconazole resistance was infrequent. Most of the patients (97%) did not have neutropenia. At the end of intravenous therapy, treatment was successful in 75.6% of patients treated with anidulafungin, as compared with 60.2% of those treated with fluconazole (difference, 15.4 percentage points; 95% confidence interval [CI], 3.9 to 27.0). The results were similar for other efficacy end points. The statistical analyses failed to show a "center effect"; when data from the site enrolling the largest number of patients were removed, success rates at the end of intravenous therapy were 73.2% in the anidulafungin group and 61.1% in the fluconazole group (difference, 12.1 percentage points; 95% CI, -1.1 to 25.3). The frequency and types of adverse events were similar in the two groups. The rate of death from all causes was 31% in the fluconazole group and 23% in the anidulafungin group (P=0.13).
CONCLUSIONS
Anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. (ClinicalTrials.gov number, NCT00056368 [ClinicalTrials.gov]).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anidulafungin; Antifungal Agents; Candida; Candidiasis; Double-Blind Method; Echinocandins; Female; Fluconazole; Fungemia; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Peptides, Cyclic; Treatment Outcome
PubMed: 17568028
DOI: 10.1056/NEJMoa066906 -
The New England Journal of Medicine Sep 2007
Topics: Anidulafungin; Antifungal Agents; Candidiasis; Confidence Intervals; Echinocandins; Fluconazole; Humans; Peptides, Cyclic; Research Design
PubMed: 17898107
DOI: 10.1056/NEJMc071981 -
The New England Journal of Medicine Sep 2007
Topics: Administration, Oral; Analysis of Variance; Anidulafungin; Antifungal Agents; Candidiasis; Catheterization, Central Venous; Echinocandins; Fluconazole; Humans; Infusions, Intravenous; Peptides, Cyclic; Time Factors
PubMed: 17902202
DOI: No ID Found