New antimicrobial agents for the treatment of Gram-positive bacterial infections

Abstract

Since the 1970s, resistance to antimicrobial agents has become an escalating problem. In the last 25 years, treatment of infections caused by Gram-positive bacteria has been more problematical than ever, with infections being caused by multidrug-resistant organisms, particularly methicillin-resistant staphylococci, penicillin- and erythromycin-resistant pneumococci, and vancomycin-resistant enterococci. There is a continuing effort in the pharmaceutical industry to develop new antimicrobial agents for the treatment of resistant infections. Linezolid, quinupristin-dalfopristin, daptomycin, tigecyline, new glycopeptides and ceftobiprole are the main agents recently introduced or under clinical development. This review summarises their major properties, the results of recent studies with these agents, and future treatment possibilities.

Molecular Basis and Phenotype of Methicillin Resistance in Staphylococcus aureus and Insights into New β-Lactams That Meet the Challenge

“…The inhibition of cell wall biosynthesis by the glycopeptides results from their stable noncovalent binding to the D-Ala-D-Ala termini of peptidoglycan precursors. Some MRSA strains have evolved resistance to vancomycin (94,159 (2). Inhibition of protein, RNA, DNA, peptidoglycan, lipoteichoic acid, and lipid biosynthesis are also observed, although it is not yet clear if these are consequences of the loss of the transmembrane electrical potential gradient or the independent effects of daptomycin.…”

Synergism between a Novel Chimeric Lysin and Oxacillin Protects against Infection by Methicillin-Resistant Staphylococcus aureus

“…To combat this challenge, the development of new and effective antibiotics belonging to different classes are being aggressively pursued. A number of new antimicrobial agents, such as linezolid, quinupristin-dalfopristin, daptomycin, telavancin, new glycopeptides, and ceftobiprole, have been introduced or are under clinical development (1). However, clinical isolates of MRSA with resistance to these new classes of antibiotics have been reported already (25,38,41).…”

In Vitro Activity of Gallium Maltolate against Staphylococci in Logarithmic, Stationary, and Biofilm Growth Phases: Comparison of Conventional and Calorimetric Susceptibility Testing Methods

“…In the biofilm, bacteria can persist in a low metabolic, stationary growth phase, in which they resist killing by the host immune system and antimicrobials (14,28). Both the spread of multiresistant staphylococci and the increased use of temporary implants (vascular catheters, pins from external fixation devices) and permanent implants (e.g., joint prosthesis, breast implants, and cardiac or brain pacemakers), drive the need for new antimicrobial agents for innovative therapeutic strategies (1,7,23,29).…”