Medical claims and current applications of the potent echinocandin antifungals.
ABSTRACT Echinocandins are an interesting group of antifungals that were originally discovered in the early 1970s. They are a group of lipopeptides produced by fungi which consists of a large number of structural analogs of echinocandin B, the first echinocandin to be structurally characterized. All clinically used echinocandins are produced semi-synthetically. The cyclic peptide nuclear core is retained while the acyl chain is replaced to minimize toxicity and expand their spectrum of activity. It was not until 2002 with the introduction of caspofungin (Cancidas) into the clinics that their true worth was realized. Since the introduction of caspofungin, two other echinocandins, micafungin (Mycamine) and anidulafungin (Eraxis) have been introduced. They all function by inhibiting an enzyme unique for fungal cell wall production, which presumably accounts for their minimal side-effects. In this review, topics pertaining to their production, structural diversity, and use in the clinic along with the recent patents are discussed.
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ABSTRACT: There is a clinical need for new treatment options for serious Gram-positive infections. Recently introduced agents such as the newer fluoroquinolones and the ketolide telithromycin have limited use as they do not cover methicillin-resistant Staphylococcus aureus (MRSA) or glycopeptide-resistant enterococci (GRE). The clinical use of the streptogramin combination quinupristin/dalfopristin, which has activity against MRSA and vancomycin-resistant Enterococcus faecium, is limited because administration is via a slow infusion of a large volume. The oxazolidinone linezolid is active against MRSA and GRE but resistant organisms and treatment failures have been reported. A number of compounds currently in development show promise, the new glycopeptides oritavancin, dalbavancin and the glycolipodepsipeptide ramoplanin, as well as the new tetracyclines tigecycline and BAY73-7388. However, in some cases, there is concern that resistance may develop quickly to new compounds that are based on existing antimicrobial agents. Therefore daptomycin, a novel lipopeptide with a unique mode of action, is of particular interest. Daptomycin is active against MRSA (including vancomycin-resistant strains) and GRE. Daptomycin displays rapid concentration-dependent killing and is bactericidal even in the stationary phase of growth. Daptomycin-resistant strains are very difficult to generate in vitro. A dosage of 4 mg/kg intravenous once a day has been shown to be efficacious in two evaluator-blinded trials of complicated skin and soft tissue infections with clinical success rates similar for daptomycin and comparators (vancomycin or penicillinase-resistant penicillins). With its activity against key Gram-positive pathogens, including resistant strains, daptomycin has potential as a valuable addition to the available treatment options for serious Gram-positive infections.Clinical Microbiology and Infection 06/2005; 11 Suppl 3:36-42. · 5.20 Impact Factor