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Clinical Drug Investigation Nov 2011Invasive fungal infections are associated with a poor outcome and their incidence is rising. Amphotericin B has for a long time been the gold standard for treatment of... (Review)
Review
Invasive fungal infections are associated with a poor outcome and their incidence is rising. Amphotericin B has for a long time been the gold standard for treatment of these infections, but the conventional formulation is associated with a high incidence of adverse events. Lipid formulations of amphotericin, developed to overcome these drawbacks, are now routinely used in clinical practice for the treatment of invasive fungal infections in immunocompromised patients. Amphotericin B lipid complex (ABLC) is prepared from amphotericin complexed to two phospholipids, a process that confers a number of important pharmacodynamic and pharmacokinetic properties compared with conventional amphotericin B. The results of retrospective observational studies and the analysis of databases, including the large Collaborative Exchange of Antifungal Research (CLEAR) database, have shown ABLC to be associated with response rates of up to about 80% in patients with confirmed fungal infections and around 60% in those treated empirically. Intranasal administration of ABLC for prophylaxis of invasive fungal infection in immunocompromised patients is safe and appears to be a promising treatment strategy for the future. ABLC is associated with a substantially lower incidence of nephrotoxicity than conventional amphotericin. Infusion-related reactions also occur less frequently than with conventional amphotericin and can be managed using premedication protocols. When direct and indirect costs are measured, ABLC appears to be less expensive than conventional amphotericin. The number of approved antifungal agents that are effective treatments for invasive fungal infections is increasing. However, lipid formulations of amphotericin, such as ABLC, are effective and well tolerated and remain the standard of care in the treatment of invasive fungal infections. Treatment strategies such as intranasal administration for prophylaxis and combination therapy with newer agents are future directions for these agents.
Topics: Amphotericin B; Antifungal Agents; Humans; Immunocompromised Host; Mycoses
PubMed: 21888451
DOI: 10.2165/11593760-000000000-00000 -
The Journal of Infection May 1994The unilamellar liposomal formulation of amphotericin B, AmBisome, is composed of hydrogenated soy phosphatidylcholine, distearoyl phosphatidylglycerol and cholesterol.... (Comparative Study)
Comparative Study Review
The unilamellar liposomal formulation of amphotericin B, AmBisome, is composed of hydrogenated soy phosphatidylcholine, distearoyl phosphatidylglycerol and cholesterol. Early studies of its efficacy in an open design showed that remissions could be induced in candidosis and aspergillosis and that doses of up to 5 mg/kg could be used. Adverse events were infrequent, with the main abnormality seen being hypokalaemia in about 18% of patients. Subsequent developments have extended this work. AmBisome has been used in two open studies of patients with invasive aspergillosis; in one of these remission was achieved in 77% of 17 patients with confirmed infection who had failed to respond to conventional amphotericin B. In AIDS patients with cryptococcosis AmBisome given for 6 weeks at 3 mg/kg daily produced mycological remission of meningitis in 67%. Other infections treated with the drug include zygomycete (mucormycosis) and Fusarium infections. AmBisome has also been used as preventative therapy in bone marrow transplant recipients and was found to reduce fungal colonisation rates. There were fewer systemic fungal infections in the treated versus placebo groups although this did not achieve statistical significance. Lack of renal and liver toxicity or anaemia has been confirmed in subsequent studies. In addition febrile reactions to the AmBisome are rare. The drug has also been used effectively in children, including infants, with systemic fungal infections. In visceral leishmaniasis patients, including HIV positive individuals, remissions have been obtained using drug regimens of 1-2 mg/kg of 2.1 days and 3 mg/kg for 10 days.
Topics: Amphotericin B; Aspergillosis; Clinical Trials as Topic; Cost-Benefit Analysis; Cryptococcosis; Drug Carriers; Humans; Liposomes; Mycoses
PubMed: 8077689
DOI: 10.1016/s0163-4453(94)95956-0 -
Drug Delivery Nov 2017Amphotericin B (AmB) remains the "gold standard" for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has... (Review)
Review
Amphotericin B (AmB) remains the "gold standard" for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has negligible oral absorption as a consequence of its unfavorable physicochemical characterizations, its use is restricted to parenteral administration which is accompanied by severe side effects. As greater understanding of the gastrointestinal tract has developed, the advanced drug delivery systems are emerging with the potential to overcome the barriers of AmB oral delivery. Much research has demonstrated that oral AmB formulations such as lipid formulations may have beneficial therapeutic efficacy with reduced adverse effects and suitable for clinical application. Here we reviewed the different formulation strategies to enhance oral drug efficacy, and discussed the current trends and future perspectives for AmB oral administration in the treatment of antifungal infections.
Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Biological Availability; Drug Compounding; Drug Delivery Systems; Gastrointestinal Absorption; Humans; Liposomes; Solubility
PubMed: 28155335
DOI: 10.1080/10717544.2016.1225852 -
Journal de Mycologie Medicale Nov 2022The challenges of the invasive infections caused by the resistant Aspergillus species include the limited access to antifungals for treatment and high mortality. This... (Review)
Review
The challenges of the invasive infections caused by the resistant Aspergillus species include the limited access to antifungals for treatment and high mortality. This study aimed to provide a global perspective of the prevalence of amphotericin B resistance (AmBR), geographic distribution, and the trend of AmBR from 2010 to 2020. To analyze the prevalence of in vitro AmBR in clinical Aspergillus species, we reviewed the literature and identified a total of 72 articles. AmBR was observed in 1128 out of 3061 Aspergillus terreus (36.8%), 538 out of 3663 Aspergillus flavus (14.9%), 141 out of 2691 Aspergillus niger (5.2%), and 353 out of 17,494 Aspergillus fumigatus isolates (2.01%). An increasing trend in AmB-resistant isolates of A. fumigatus and a decreasing trend in AmB-resistant A. terreus and A. flavus isolates were observed between 2016 and 2020. AmB-resistant A. terreus and A. niger isolates, accounting for 40.4% and 20.9%, respectively, were the common AmB-resistant Aspergillus species in Asian studies. However, common AmB-resistant Aspergillus species reported by European and American studies were A. terreus and A. flavus isolates, accounting for 40.1% and 14.3% in 31 studies from Europe and 25.1% and 11.7% in 14 studies from America, respectively. The prevalence of AmB-resistant A. niger in Asian isolates was higher than in American and European. We found a low prevalence of A. terreus in American isolates (25.1%) compared to Asian (40.4%) and European (40.1%). Future studies should focus on analyzing the trend of AmBR on a regional basis and using the same methodologies.
Topics: Amphotericin B; Prevalence; Microbial Sensitivity Tests; Aspergillus; Antifungal Agents; Drug Resistance, Fungal
PubMed: 35907396
DOI: 10.1016/j.mycmed.2022.101310 -
Reviews of Infectious Diseases 1990Amphotericin B, the first commercially significant antifungal drug, has been available for more than 30 years. This polyene macrolide antifungal agent continues to play... (Review)
Review
Amphotericin B, the first commercially significant antifungal drug, has been available for more than 30 years. This polyene macrolide antifungal agent continues to play a major role in the treatment of systemic fungal infections, despite the introduction of newer agents such as the azoles. Given the proved efficacy of amphotericin B--and the increasing number of indications for antifungal agents--an extensive review of this drug is warranted. This paper discusses the clinical uses of amphotericin B, including its application in AIDS-related fungal infections, in neutropenic cancer patients who are persistently febrile, and in infections of the central nervous system, lung, peritoneum, genitourinary system, eye, and skin. The paper also reviews the drug's adverse reactions, with a discussion of administration techniques that may reduce these reactions, and its spectrum of activity, pharmacokinetics, and dosage and administration.
Topics: Amphotericin B; Animals; Drug Interactions; Humans; Mycoses
PubMed: 2184499
DOI: 10.1093/clinids/12.2.308 -
British Journal of Biomedical Science Jun 1996Amphotericin B is the most important clinically and best defined chemically of the macrolide heptaene antibiotics. A fermentation product of the soil actinomycetes... (Review)
Review
Amphotericin B is the most important clinically and best defined chemically of the macrolide heptaene antibiotics. A fermentation product of the soil actinomycetes Streptomyces nodosus, amphotericin B binds selectively to ergosterol in the cell membrane of susceptible fungi, inducing changes in permeability that can produce lethal cell injury. Available since 1960, amphotericin B remains the treatment of choice for most serious systemic fungal infections. This review highlights some important aspects of the physicochemical properties of amphotericin B and their utilisation in its quantitative determination in biological fluids. Its mechanism of action is re-appraised in the light of recent results with regard to its effects on the physical and functional properties of synthetic and natural membranes. Attempts to reduce its toxic effects to host cells and to improve its therapeutic index are evaluated. In addition, the therapeutic values of amphotericin B, apart from its antibiotic activity, are discussed.
Topics: Amphotericin B; Antifungal Agents; Drug Carriers; Drug Synergism; Humans; Immune System; Liposomes
PubMed: 8757689
DOI: No ID Found -
Medical Mycology Mar 2016Given the clinical success of commercial amphotericin B lipid products, investigators have begun making generic formulations of liposomal amphotericin B. Generic... (Comparative Study)
Comparative Study Review
Given the clinical success of commercial amphotericin B lipid products, investigators have begun making generic formulations of liposomal amphotericin B. Generic medicines are an attractive approach to help decrease the cost and accessibility to healthcare, provided that appropriate studies are performed to ensure bioequivalence with the parent product. This is of particular concern for liposomal drugs such as amphotericin B where liposomes are used as a carrier system to reduce the toxicity of the active agent. A favorable therapeutic profile for this form of the drug has to include the proper chemical composition along with strictly controlled manufacturing processes. Studies have shown that a comparison of liposomal amphotericin B products with different or the same chemical compositions, using different methods of production, will vary in size, and have significantly dissimilar in vitro and in vivo toxicities along with reduced efficacy. These results underscore the importance of establishing appropriate bioequivalence testing for liposome products to ensure uniformity of their therapeutic index.
Topics: Amphotericin B; Antifungal Agents; Drug Compounding; Humans; Therapeutic Equivalency
PubMed: 26768369
DOI: 10.1093/mmy/myv111 -
The Journal of Antimicrobial... Feb 1994Despite the introduction in recent years of novel antifungal agents, the potency and broad spectrum of activity of amphotericin B have ensured that it remains the... (Review)
Review
Despite the introduction in recent years of novel antifungal agents, the potency and broad spectrum of activity of amphotericin B have ensured that it remains the treatment of choice for most deep-seated mycoses. However, this agent is not without significant toxicity, particularly in patients who are already seriously ill and/or who are receiving other potentially nephrotoxic drugs. We review the various routes by which amphotericin B can be administered, focusing mainly on the intravenous route. The use of more rapid infusion rates, lipid-complexed preparations, sodium supplementation in salt-depleted patients and strategies to reduce the incidence of infusion-related reactions and nephrotoxicity are also considered. Finally, detailed recommendations for the administration of amphotericin B are provided.
Topics: Amphotericin B; Chemistry, Pharmaceutical; Drug Administration Routes; Drug Interactions; Fungi; Humans; Infusions, Intravenous; Kidney Diseases; Mycoses
PubMed: 8182001
DOI: 10.1093/jac/33.2.203 -
Drug and Therapeutics Bulletin Nov 1993
Review
Topics: Amphotericin B; Animals; Drug Carriers; Humans; Liposomes; Mycoses
PubMed: 8293696
DOI: No ID Found -
Current Topics in Medicinal Chemistry 2022Over the last 50 years, the number of patients with mycotic infections has gradually increased. Amphotericin-B is a gold-standard drug used in serious systemic fungal... (Review)
Review
Over the last 50 years, the number of patients with mycotic infections has gradually increased. Amphotericin-B is a gold-standard drug used in serious systemic fungal infections. However, limited solubility and permeability are challenging issues associated with Amphotericin-B. Chemical modification is one of the ways to get its broader applicability and improved physicochemical properties. The review article provides a comprehensive overview of the chemical modification approach for investigating the mechanism of action, biological activity, bioavailability, and toxicity of Amphotericin B. Further, several drug delivery approaches have also been utilized to provide better therapeutic outcomes. This gives an overview of chemical approaches for exploring various factors associated with Amphotericin B and information on its drug delivery approaches for improved biopharmaceutical outcomes.
Topics: Amphotericin B; Antifungal Agents; Biological Products; Drug Delivery Systems; Humans; Mycoses
PubMed: 35692126
DOI: 10.2174/1568026622666220610141243