Newer Treatment Options for Skin and Soft Tissue Infections

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Abstract
In recent years, serious skin and soft tissue infections (SSTIs) caused by multidrug resistant pathogens have become more common. While the majority of SSTIs are caused by Staphylococcus aureus or β-haemolytic streptococci that are methicillin/oxacillin susceptible, the emergence of methicillin-resistant and vancomycin-resistant community-acquired and nosocomial Gram-positive pathogens has created a need for different therapeutic agents, such as linezolid, quinupristin/dalfopristin, daptomycin, and newer generation carbapenems and fluoroquinolones. This review focuses on agents presently in clinical development for the treatment of SSTIs caused by Gram-positive pathogens such as staphylococci, streptococci and enterococci including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE). Newer-generation carbapenems, such as meropenem and ertapenem, are characterised by a broad-spectrum of activity against Gram-positive and -negative aerobes and anaerobes, and are resistant to hydrolysis by many β-lactamases. Current-generation fluoroquinolones, such as levofloxacin, moxifloxacin and gatifloxacin, have demonstrated better eradication rates for S. aureus than conventional penicillin and cephalosporins. These antimicrobial agents can be used to treat methicillin-susceptible staphylococcal and streptococcal strains. Oxazolidinones, streptogramin combinations and cyclic lipopeptides have novel mechanisms of action and have been studied in several multinational phase III clinical trials in the treatment of complicated and uncomplicated SSTIs. They possess a broad spectrum of activity against multidrug-resistant pathogens, including MRSA and VRE. Linezolid has been shown to be active against a wide variety of community-acquired and nosocomial antimicrobial-resistant pathogens with comparability to vancomycin, as well as resulting in reduced lengths of hospital stay. Cyclic lipopeptides such as daptomycin have a unique mechanism of action by disruption of bacterial membrane electric potentials with less likelihood for development of cross-resistance. Daptomycin has recently been US FDA approved for the treatment of complicated SSTI. However, rapid development of resistance to some of these newer agents has already been reported and this trend magnifies the importance of further need for effective antimicrobial agents. Several investigational agents, such as dalbavancin, oritavancin and tige-cycline, are in advanced stages of development and are likely to proceed to licensing in the next few years. With their long half-lives, these agents have an advantage of less frequent dose administration with more rapid bactericidal activity and less likelihood for development of resistance. However, because of their proven activity against highly resistant organisms, these antibacterial agents should be reserved only for life-threatening situations and/or when resistant pathogens are suspected. Rational antimicrobial use coupled with awareness of infection control measures is paramount to avert the emergence of multidrug-resistant organisms.