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      Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review

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          Abstract

          Increasing rates of antimicrobial resistance among strains of Streptococcus, Staphylococcus, and Enterococcus spp. have been widely documented. At least 50% of nosocomial Staphylococcus aureus infections in intensive care units in the US and UK are due methicillin-resistant S. aureus (MRSA). Drug resistance is not confined to hospitals, and community-acquired MRSA (CA-MRSA) strains are now common causes of complicated skin and soft-tissue infections (cSSTIs) in many regions. Dalbavancin is a novel parenterally administered semisynthetic lipoglycopeptide similar to the naturally produced glycopeptides vancomycin and teicoplanin. Dalbavancin features a multifaceted mechanism of action that inhibits bacterial cell wall formation by two different mechanisms that enhances its activity against a wide range of gram-positive bacteria including staphylococci, streptococci, enterococci, and some anaerobes. Additionally, dalbavancin possesses unique pharmacokinetic properties, the most significant of which is a long terminal half-life that allows for once weekly dosing. This attribute may prove to yield clinical and cost benefit. Overall, clinical trials indicate that dalbavancin is a safe, well-tolerated, and effective antimicrobial agent. In the largest investigation evaluating dalbavancin for the treatment of cSSTIs, it appeared to be as effective as linezolid. Dalbavancin, which is expected to receive FDA approval in 2008, appears to be a promising new antimicrobial agent for the treatment of cSSTIs.

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          Most cited references 68

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          Methicillin-resistant S. aureus infections among patients in the emergency department.

          Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized in infections among persons in the community without established risk factors for MRSA. We enrolled adult patients with acute, purulent skin and soft-tissue infections presenting to 11 university-affiliated emergency departments during the month of August 2004. Cultures were obtained, and clinical information was collected. Available S. aureus isolates were characterized by antimicrobial-susceptibility testing, pulsed-field gel electrophoresis, and detection of toxin genes. On MRSA isolates, we performed typing of the staphylococcal cassette chromosome mec (SCCmec), the genetic element that carries the mecA gene encoding methicillin resistance. S. aureus was isolated from 320 of 422 patients with skin and soft-tissue infections (76 percent). The prevalence of MRSA was 59 percent overall and ranged from 15 to 74 percent. Pulsed-field type USA300 isolates accounted for 97 percent of MRSA isolates; 74 percent of these were a single strain (USA300-0114). SCCmec type IV and the Panton-Valentine leukocidin toxin gene were detected in 98 percent of MRSA isolates. Other toxin genes were detected rarely. Among the MRSA isolates, 95 percent were susceptible to clindamycin, 6 percent to erythromycin, 60 percent to fluoroquinolones, 100 percent to rifampin and trimethoprim-sulfamethoxazole, and 92 percent to tetracycline. Antibiotic therapy was not concordant with the results of susceptibility testing in 100 of 175 patients with MRSA infection who received antibiotics (57 percent). Among methicillin-susceptible S. aureus isolates, 31 percent were USA300 and 42 percent contained pvl genes. MRSA is the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities. When antimicrobial therapy is indicated for the treatment of skin and soft-tissue infections, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage. Copyright 2006 Massachusetts Medical Society.
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            Methicillin-resistant Staphylococcus aureus disease in three communities.

            Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. The national burden and clinical effect of this novel presentation of MRSA disease are unclear. We evaluated MRSA infections in patients identified from population-based surveillance in Baltimore and Atlanta and from hospital-laboratory-based sentinel surveillance of 12 hospitals in Minnesota. Information was obtained by interviewing patients and by reviewing their medical records. Infections were classified as community-associated [correction] MRSA disease if no established risk factors were identified. From 2001 through 2002, 1647 cases of community-associated [correction] MRSA infection were reported, representing between 8 and 20 percent of all MRSA isolates. The annual disease incidence varied according to site (25.7 cases per 100,000 population in Atlanta vs. 18.0 per 100,000 in Baltimore) and was significantly higher among persons less than two years old than among those who were two years of age or older (relative risk, 1.51; 95 percent confidence interval, 1.19 to 1.92) and among blacks than among whites in Atlanta (age-adjusted relative risk, 2.74; 95 percent confidence interval, 2.44 to 3.07). Six percent of cases were invasive, and 77 percent involved skin and soft tissue. The infecting strain of MRSA was often (73 percent) resistant to prescribed antimicrobial agents. Among patients with skin or soft-tissue infections, therapy to which the infecting strain was resistant did not appear to be associated with adverse patient-reported outcomes. Overall, 23 percent of patients were hospitalized for the MRSA infection. Community-associated MRSA infections are now a common and serious problem. These infections usually involve the skin, especially among children, and hospitalization is common. Copyright 2005 Massachusetts Medical Society.
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              Practice guidelines for the diagnosis and management of skin and soft-tissue infections.

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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                February 2008
                February 2008
                : 4
                : 1
                : 31-40
                Affiliations
                [1 ]Department of Medicine-Infectious Disease Service, Brooke Army Medical Center Fort Sam Houston, TX, USA
                [2 ]Department of Medicine-Division of Infectious Diseases, University of Texas Health Science Center San Antonio, TX, USA
                Author notes
                Correspondence: Michael W Ellis Brooke Army Medical Center, Infectious Disease Service (MCHE-MDI), 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA Tel +1 210 916 4355 Fax +1 210 916 0388 Email michael.w.ellis@ 123456us.army.mil
                Article
                2503664
                18728718
                © 2008 Dove Medical Press Limited. All rights reserved
                Categories
                Review

                Medicine

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