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Amphotericin B lipid complex in the management of invasive fungal infections in immunocompromised patients.

Clinical drug investigation (2011-09-06)
Matteo Bassetti, Franco Aversa, Filippo Ballerini, Fabio Benedetti, Alessandro Busca, Nicola Cascavilla, Ercole Concia, Andrea Tendas, Francesco Di Raimondo, Patrizio Mazza, Anna Maria Nosari, Giuseppe Rossi
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Amphotericin B solubilized, powder, γ-irradiated, BioXtra, suitable for cell culture
Amphotericin B for microbiological assay, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Amphotericin B from Streptomyces sp., ~80% (HPLC), powder
Sigma-Aldrich
Amphotericin B from Streptomyces sp., BioReagent, suitable for cell culture, ~80% (HPLC)
Supelco
Amphotericin B trihydrate, VETRANAL®, analytical standard
Amphotericin B for peak identification, European Pharmacopoeia (EP) Reference Standard
Amphotericin B, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Amphotericin B solution, 250 μg/mL in deionized water, 0.1 μm filtered, BioReagent, suitable for cell culture