Serious staphylococcal infections—cyclic lipopeptides: meeting new challenges

Abstract

This supplement is based on the proceedings of the symposium entitled ‘Serious staphylococcal infections—cyclic lipopeptides: meeting new challenges’, which was presented at the 17th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Munich during April 2007. An increasing proportion of serious bacterial infections are attributable to Gram-positive bacteria [1,2]. Of these, Staphylococcus aureus is of particular clinical significance, as both a community-acquired and hospital-acquired pathogen that is associated with high morbidity and mortality rates, and for which the incidence of antibiotic resistance is increasing [3]. As a consequence, S. aureus represents a significant healthcare burden; in the USA, excess costs, length of hospitalisation and inpatient deaths due to S. aureus are estimated at $9.5 billion, 2.7 million days and 12 000 patients per year, respectively [4]. In a study of 74 patients with methicillinresistant S. aureus (MRSA) infections at Vienna General Hospital in 2002, there were nine deaths, the median hospital stay was 37 days, and the median total hospital cost was £6624 [5]. Common infections related to this species include complicated skin and soft-tissue infections (cSSTIs), bacteraemia and infective endocarditis. Today’s challenge for the clinician is how to treat Grampositive bacterial infections effectively, given the increasing diversity of drug-resistant pathogens and the diminishing treatment options. The cyclic lipopeptides are the latest new drug class with activity against resistant staphylococci, and clinical data suggest that daptomycin, the first licensed member, may contribute substantially to meeting this challenge. Daptomycin is currently licensed by the European Medicines Agency for the treatment of cSSTIs, right-sided endocarditis caused by S. aureus and S. aureus bacteraemia (SAB) when associated with rightsided endocarditis or with cSSTIs. It is also licensed in the USA for the treatment of cSSTIs and SAB, including SAB associated with rightsided endocarditis. The opening article of this supplement focuses on the growing problem of antibiotic resistance among Gram-positive bacteria, in particular MRSA, and the impact on traditional therapeutic approaches. Hospital-acquired MRSA became endemic in many hospitals during the 1980s; however, the problem is no longer confined to the healthcare setting, with new MRSA strains emerging in the community (community-acquired MRSA) in healthy individuals [6]. The glycopeptides, in particular vancomycin, are currently the standard-of-care antibiotics for MRSA infections. However, their extensive use has led to the emergence of vancomycin-resistant and -intermediate S. aureus (VRSA and VISA, respectively) strains. The utility of vancomycin therapy in S. aureus infections is also threatened by vancomycin tolerance and rising MICs associated with treatment failures. In the second article, the antimicrobial characteristics of daptomycin are described, and there is a review of phase III clinical data concerning the treatment of cSSTIs [7]. In-vitro experiments with daptomycin, which is bactericidal without being bacteriolytic, have confirmed a rapid and broadspectrum activity against Gram-positive organisms. Daptomycin was shown not to be inferior to the comparator regimens (vancomycin and penicillinase-resistant penicillins) for the treatment of both methicillin-sensitive S. aureus (MSSA) and MRSA cSSTIs [7]. Compared with comparator therapies, a significant difference in favour of Corresponding author and reprint requests: W. Graninger, Universitatsklinik fur Innere Medizin I, Ableitung fur Infektionen und Chemotherapie, Wahringer Gurtel 18-20, A-1090 Vienna, Austria E-mail: wolfgang.graninger@meduniwien.ac.at