Introduction: the modern gladiatorial arena: Gram-positive pathogens versus new therapies

Abstract

Three of the papers contained in this supplement cover aspects of a symposium titled ‘The modern gladiatorial arena: Gram-positive pathogens versus new therapies’ which was held at the 14th European Congress of Clinical Microbiology and Infectious Diseases in Prague, Czech Republic, in May 2004. These papers review the prevalence of resistant pathogens in Europe, the effectiveness of currently available therapies, areas of unmet clinical need, and the way in which unmet needs might be addressed in the future. They are preceded by a fourth paper which provides a review of the mechanisms of antibiotic resistance in Gram-positive bacteria. One of the antibiotics that promises to be relevant to unmet needs is daptomycin, an agent with a unique mode of bactericidal action. The antibiotic was discovered by Eli Lilly and Company (Lilly) in the early 1980s and was under development as LY146032, for the intravenous treatment of serious Gram-positive infections. Despite promising trials for the treatment of skin and soft tissue infections and endocarditis Lilly suspended trials in 1991 because of concerns regarding skeletal muscle toxicity. Later in the decade, interest in daptomycin returned because of the increasing prevalence of infections caused by Gram-positive pathogens that were resistant to many antibiotics. In 1997, Cubist Pharmaceuticals received rights to the drug on the premise that modified dosing regimens would be clinically effective without the risk of skeletal muscle toxicity. Clinical trials (at a dosage of 4 mg/kg once daily) supported this premise and in September 2003 the drug was approved by the US Food and Drug Administration for the treatment of complicated skin and soft tissue infections caused by susceptible Gram-positive bacteria, including methicillin-resistant and methicillinsusceptible Staphylococcus aureus. Chiron Biopharmaceuticals has in-licensed the commercial rights to daptomycin in Western and Eastern Europe, Australia, New Zealand, India and certain Central American, South American and Middle Eastern countries. Daptomycin is currently undergoing further trials to assess its potential to address unmet needs, particularly in the treatment of serious skin and soft tissue infections.