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Medecine Et Maladies Infectieuses Aug 2010The increasing incidence of invasive fungal infections, epidemiological changes in these infections, and safety or interactions issues that might limit the use of... (Review)
Review
The increasing incidence of invasive fungal infections, epidemiological changes in these infections, and safety or interactions issues that might limit the use of traditional antifungal therapies explain the need for new antifungal agents. Anidulafungin is a new echinocandin with excellent activity on most Candida as well as on Aspergillus species. Its pharmacokinetic properties allow its administration without dosage adjustments in patients with hepatic and renal impairment and account for the absence of drug interactions. Anidulafungin has showed its efficacy and good tolerability in systemic candidiasis of non-neutropenic adults, including candidemia especially in fragile patients.
Topics: Anidulafungin; Animals; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Echinocandins; Humans
PubMed: 20096516
DOI: 10.1016/j.medmal.2009.12.002 -
Drugs in R&D 2003Vicuron Pharmaceuticals (formerly Versicor Inc.) is developing anidulafungin [LY 303366, ECB, V-echinocandin, VEC, VER-02, VER 002], a lipopeptide echinocandin B... (Review)
Review
Vicuron Pharmaceuticals (formerly Versicor Inc.) is developing anidulafungin [LY 303366, ECB, V-echinocandin, VEC, VER-02, VER 002], a lipopeptide echinocandin B derivative, for IV treatment of mycoses. Anidulafungin acts against fungal infection by inhibiting beta-1,3-glucan synthase, an enzyme essential for cell wall formation. Anidulafungin was originally developed for oral use by Eli Lilly and was undergoing phase II clinical trials in the UK and the US for the treatment of Candida, Aspergillus and Pneumocystis carinii infections. However, Eli Lilly discontinued development of the oral formulation due to poor oral bioavailability. In May 1999, Versicor obtained exclusive worldwide commercialisation rights to anidulafungin with responsibility for its development and clinical registration. Under the terms of the agreement, Eli Lilly received a signing fee, and will receive milestone payments upon future development of anidulafungin and royalties on future sales. Eli Lilly also retains an option for the development of an oral formulation of the compound. On 3 March 2003, Versicor Inc. of Fremont (California, USA) and Biosearch Italia SpA of Milan (Italy) announced the completion of a merger agreement, whereby Biosearch was merged with and into Versicor in a stock-for-stock exchange valued at US dollars 260.7 million. The combined company temporarily kept the name Versicor until the new name, Vicuron Pharmaceuticals, was announced on 26 March 2003. In January 2003, Versicor announced that positive results from a phase II trial for anidulafungin IV treatment involving 120 patients in the US with invasive candidiasis/candidaemia, have led to another double-blind, randomised phase III trial being conducted in the US, Canada and Europe for this indication. This additional phase III trial will enrol approximately 300 patients to investigate the efficacy of IV anidulafungin (200 mg loading dose followed by 100 mg maintenance dose) versus IV fluconazole for 10 to 42 days. Vicuron Pharmaceuticals also plans to seek approval for invasive candidiasis/candidaemia in Europe and Canada in the second half of 2003.
Topics: Anidulafungin; Animals; Antifungal Agents; Candida; Candidiasis; Clinical Trials as Topic; Drugs, Investigational; Echinocandins; Humans; Peptides, Cyclic; Saccharomyces cerevisiae
PubMed: 12757403
DOI: 10.2165/00126839-200304030-00005 -
Antimicrobial Agents and Chemotherapy Jun 2023Candida auris is an emerging, multidrug-resistant fungal pathogen that causes refractory colonization and life-threatening, invasive nosocomial infections. The high...
Candida auris is an emerging, multidrug-resistant fungal pathogen that causes refractory colonization and life-threatening, invasive nosocomial infections. The high proportion of C. auris isolates that display antifungal resistance severely limits treatment options. Combination therapies provide a possible strategy by which to enhance antifungal efficacy and prevent the emergence of further resistance. Therefore, we examined drug combinations using antifungals that are already in clinical use or are undergoing clinical trials. Using checkerboard assays, we screened combinations of 5-flucytosine and manogepix (the active form of the novel antifungal drug fosmanogepix) with anidulafungin, amphotericin B, or voriconazole against drug resistant and susceptible C. auris isolates from clades I and III. Fractional inhibitory concentration indices (FICI values) of 0.28 to 0.75 and 0.36 to 1.02 were observed for combinations of anidulafungin with manogepix or 5-flucytosine, respectively, indicating synergistic activity. The high potency of these anidulafungin combinations was confirmed using live-cell microfluidics-assisted imaging of the fungal growth. In summary, combinations of anidulafungin with manogepix or 5-flucytosine show great potential against both resistant and susceptible C. auris isolates.
Topics: Antifungal Agents; Anidulafungin; Flucytosine; Candida auris; Candida; Microbial Sensitivity Tests
PubMed: 37162367
DOI: 10.1128/aac.01645-22 -
Journal of Biomedical Materials... Nov 2020Fungal infections can cause significant patient morbidity and mortality. Nanoparticle therapeutics have the potential to improve treatment of these infections. Here we...
Fungal infections can cause significant patient morbidity and mortality. Nanoparticle therapeutics have the potential to improve treatment of these infections. Here we report the development of liposomal nanoparticles incorporating anidulafungin, a potent antifungal, with the goal of increasing its solubility and aiding in localization to fungi. Liposomes were fabricated with three concentrations of anidulafungin yielding monodisperse ~100 nm unilamellar vesicles. All three formulations inhibited planktonic Candida albicans growth at a minimum inhibitory concentration equivalent to free drug. All three formulations also disrupted preformed C. albicans biofilms, reducing fungal burden by as much as 99%, exhibiting superior biofilm disruption compared with free drug. Liposome formulations tested in vivo in C. albicans infected Galleria mellonella wax moth larvae demonstrated increased survival compared to free drug equivalents, leading to a survival of 33 to 67% of larvae over 7 days depending on the liposome utilized compared with only 25% survival of larvae administered free drug. Liposomal formulations along with free anidulafungin did not cause red blood cell lysis. Ultimately, the liposome formulations reported here increased anidulafungin solubility, displayed promising efficacy against planktonic and biofilm C. albicans, and improved the survival of C. albicans-infected G. mellonella compared to free anidulafungin.
Topics: Anidulafungin; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Humans; Liposomes; Nanoparticles; Plankton
PubMed: 32363762
DOI: 10.1002/jbm.a.36984 -
Pharmacotherapy Jan 2009Anidulafungin is the third echinocandin antifungal agent to receive approval from the United States Food and Drug Administration. It is indicated for the treatment of... (Review)
Review
Anidulafungin is the third echinocandin antifungal agent to receive approval from the United States Food and Drug Administration. It is indicated for the treatment of esophageal candidiasis, candidemia, and other candidal infections. Anidulafungin is fungicidal against Candida species, including Candida glabrata and isolates resistant to azoles and polyenes. The drug's efficacy is comparable to that of fluconazole for the treatment of esophageal candidiasis, and it is effective in patients with invasive candidiasis and candidemia. Anidulafungin is distinct among the echinocandins in that it undergoes slow, nonenzymatic chemical degradation. As a consequence, impairments in renal or hepatic function do not substantially alter its pharmacokinetics. In addition, anidulafungin has not demonstrated any drug-drug interactions because it is not a substrate, inhibitor, or inducer of the cytochrome P450 enzyme system. Anidulafungin is well tolerated in adults and pediatric patients, with few reported adverse drug events. The safety, tolerability, and potent fungicidal activity of anidulafungin against Candida species make it a reasonable alternative in the treatment of patients with serious candidal infections.
Topics: Anidulafungin; Animals; Antifungal Agents; Candidiasis; Clinical Trials as Topic; Drug Costs; Drug Interactions; Drug Resistance, Fungal; Echinocandins; Esophageal Diseases; Humans
PubMed: 19113794
DOI: 10.1592/phco.29.1.17 -
Mycopathologia Aug 2020Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. However, there are few studies comparing anidulafungin and micafungin in terms of...
BACKGROUND
Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. However, there are few studies comparing anidulafungin and micafungin in terms of efficacy and safety. The objective of this study was to evaluate the clinical efficacy and safety between anidulafungin and micafungin treatment for adult patients with candidemia.
METHODS
This retrospective cohort study performed on adult candidemia patients diagnosed from January 2006 through December 2018 at a tertiary medical center. The study subjects included adult patients ≥ 19 years with candidemia who were only treated with anidulafungin or micafungin for ≥ 3 days. Clinical characteristics were collected and analyzed. Hepatotoxicity was assessed according to the Common Terminology Criteria for Adverse Events Version 5.0.
RESULTS
A total of 98 patients with candidemia were treated with anidulafungin (n = 52, 53.1%) or micafungin (n = 46, 46.9%). There were no significant differences in age, sex, source of candidemia, and comorbidities between the anidulafungin and micafungin groups. Although there were more patients with abnormal baseline liver function test (LFT) in the anidulafungin group, the rate of clinical response (51.9% vs. 46.7%), mycological response (76.9% vs. 67.4%), and mortality (30-day mortality 26.9% vs. 21.7% and 90-day mortality 78.8% vs. 73.9%) was similar between the anidulafungin and micafungin groups. Also, there was no significant difference in terms of hepatotoxicity, even among the patients with abnormal baseline LFT between the two groups.
CONCLUSIONS
Our results suggest that clinical efficacy and safety may be similar between anidulafungin and micafungin treatment for adult patients with candidemia.
Topics: Aged; Anidulafungin; Antifungal Agents; Candidemia; Echinocandins; Female; Humans; Lipopeptides; Male; Micafungin; Middle Aged; Retrospective Studies
PubMed: 32705415
DOI: 10.1007/s11046-020-00471-8 -
Revista Iberoamericana de Micologia Jun 2008Anidulafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses. The antifungal spectrum of anidulafungin reaches the most common... (Review)
Review
Anidulafungin is a new and very useful pharmacological tool for the treatment of invasive mycoses. The antifungal spectrum of anidulafungin reaches the most common pathogenic fungi. Anidulafungin is especially active against the genera Candida and Aspergillus. Its antifungal mechanism is based on the inhibition of the beta-1,3-D-glucan synthesis, an essential molecule for the cell wall architecture, with different consequences for Candida and Aspergillus, being anidulafungin fungicide for the former and fungistatic for the latter. This review describes the in vitro antifungal spectrum of anidulafungin based in the scientific and medical literature of recent years. We can underline that most than 99% of Candida isolates are susceptible to < or = 2 microg/ml of anidulafungin. MIC are very low (< or =0.125 microg/ml) for most clinical isolates of the species Candida albicans, Candida glabrata, Candida tropicalis and Candida krusei while Candida parapsilosis and Candida guilliermondii isolates are susceptible to anidulafungin concentrations < or = 2 microg/ml. An excellent activity of anidulafungin has been also described against Aspergillus, Pneumocystis and other fungi. However, its activity is very low against Cryptococcus and the Zygomycetes. The excellent activity of anidulafungin has made this antifungal a first line therapeutic indication for candidemia and invasive candidiasis in non-neutropenic patients.
Topics: Anidulafungin; Antifungal Agents; Echinocandins; Fungi; Microbial Sensitivity Tests
PubMed: 18473502
DOI: 10.1016/s1130-1406(08)70025-1 -
Cellular Physiology and Biochemistry :... 2016The novel antifungal drug Anidulafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. The traditional antifungal drug...
BACKGROUND/AIMS
The novel antifungal drug Anidulafungin is used for the treatment of diverse fungal infections including candidiasis and aspergillosis. The traditional antifungal drug amphotericin B has previously been shown to trigger eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, activated protein kinase C (PKC), casein kinase 1α or p38 kinase and activated caspases. Inhibitors of eryptosis include nitric oxide (NO). The present study explored, whether Anidulafungin induces eryptosis.
METHODS
Flow cytometry was employed to estimate phosphatidylserine abundance at the erythrocyte surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Hemolysis was quantified by measuring haemoglobin concentration in the supernatant.
RESULTS
A 48 hours exposure of human erythrocytes to Anidulafungin (1.5 - 6 µg/ml) significantly increased hemolysis and the percentage of annexin-V-binding cells, and significantly decreased forward scatter. Anidulafungin (6 µg/ml) slightly, but significantly inceased Fluo3-fluorescence and the effect of Anidulafungin on annexin-V-binding was slightly, but significantly blunted by removal of extracellular Ca2+. The effect of Anidulafungin on annexin-V-binding was further significantly blunted by the p38 kinase inhibitor SB203580 (2 µM) and NO donor nitroprusside (1 µM). An increase of extracellular K+ concentration significantly blunted the effect of Anidulafungin on cell volume but not on annexin-V-binding. Anidulafungin rather decreased DCFDA fluorescence and the effect of Anidulafungin on annexin-V-binding was not significantly blunted by the antioxidant N-acetylcysteine (1 mM). Moreover, the effect of Anidulafungin on annexin-V-binding was not paralleled by significant increase of ceramide abundance and was not significantly blunted by PKC inhibitor staurosporine (1 µM), casein kinase 1α inhibitor D4476 (10 µM) or pancaspase inhibitor zVAD (10 µM).
CONCLUSIONS
Anidulafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to Ca2+ entry and activation of p38 kinase.
Topics: Anidulafungin; Antifungal Agents; Calcium; Cell Size; Echinocandins; Eryptosis; Erythrocytes; Hemolysis; Humans; Reactive Oxygen Species
PubMed: 27197532
DOI: 10.1159/000445582 -
Expert Opinion on Drug Metabolism &... Oct 2010Anidulafungin is one of three available intravenous echinocandins that plays an important role in the treatment of serious fungal infections. Currently, anidulafungin is... (Review)
Review
IMPORTANCE OF THE FIELD
Anidulafungin is one of three available intravenous echinocandins that plays an important role in the treatment of serious fungal infections. Currently, anidulafungin is approved for the treatment of esophageal candidiasis, candidemia and other invasive Candida infections including intra-abdominal abscesses and peritonitis.
AREAS COVERED IN THIS REVIEW
This paper covers a comprehensive review of anidulafungin.
WHAT THE READER WILL GAIN
The reader will be provided the most recent data available regarding the pharmacology, pharmacokinetics, in vitro activity and clinical utility of anidulafungin for the treatment of serious fungal infections.
TAKE HOME MESSAGE
Echinocandin antifungals, such as anidulafungin, are now considered first line for the treatment of candidemia and invasive candidiasis, particularly in critically ill patients or those who have previously received azole therapy. Anidulafungin has potent in vitro activity against Candida and Aspergillus species, predictable pharmacokinetics that does not require dosage adjustment, few drug interactions and is well tolerated. Because of these favorable characteristics, anidulafungin is an important addition to our antifungal armamentarium.
Topics: Anidulafungin; Animals; Antifungal Agents; Aspergillosis; Candidiasis; Clinical Trials as Topic; Drug Interactions; Echinocandins; Humans; Mycoses
PubMed: 20822479
DOI: 10.1517/17425255.2010.518143 -
Expert Review of Anti-infective Therapy Aug 2004Anidulafungin (Vicuron Pharmaceuticals) is a new echinocandin antifungal with potent activity against Aspergillus and Candida spp. Anidulafungin is a noncompetitive... (Review)
Review
Anidulafungin (Vicuron Pharmaceuticals) is a new echinocandin antifungal with potent activity against Aspergillus and Candida spp. Anidulafungin is a noncompetitive inhibitor of (1,3)-beta-D-glucan synthase within fungal cells. The drug is rapidly distributed and steady-state concentrations are achieved after the first dose, when a loading dose of twice the daily maintenance dose is given on day 1. Drug biotransformation occurs via chemical degradation, with no hepatic metabolism or renal elimination. A favorable pharmacokinetic profile and lack of significant drug interactions suggest that patients can receive anidulafungin without dosage adjustments. These characteristics, in addition to comparable efficacy to fluconazole (Diflucan, Pfizer Ltd) in the treatment of esophageal candidiasis, support further investigation of its use in the treatment of systemic fungal infections caused by Candida and Aspergillus spp.
Topics: Anidulafungin; Animals; Antifungal Agents; Biotransformation; Clinical Trials as Topic; Drug Combinations; Drug Interactions; Echinocandins; Fungi; Humans; Intestinal Absorption; Kidney Diseases; Liver Diseases; Mycoses; Peptides, Cyclic; Tissue Distribution
PubMed: 15482216
DOI: 10.1586/14787210.2.4.499