The Need for New Therapeutic Agents: What Is the Pipeline?

Clin Microbiol Infect. 2005 May;11 Suppl 3:36-42. doi: 10.1111/j.1469-0691.2005.01141.x.

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.

Publication types

  • Review

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use*
  • Daptomycin / pharmacology
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Vancomycin Resistance

Substances

  • Anti-Infective Agents
  • Daptomycin