The need for new therapeutic agents: what is the pipeline?
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.
Shah
P M
PM
Klinikum der Wolfgang Goethe-Universitat, Zentrum der Inneren Medizin, Medizinische Klinik III, Schwerpunkt Infektiologie, Theodoe-Srwen-Kai 7, D-60590 Frankfurt, Germany
D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017576:Daptomycin / Q000494:pharmacology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D020713:Vancomycin Resistance
D000890:Anti-Infective Agents; D017576:Daptomycin