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      New developments in the treatment of acute bacterial skin and skin structure infections: considerations for the effective use of dalbavancin

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          Abstract

          Dalbavancin, an intravenous glycopeptide, was approved by the US Food and Drug Administration in May 2014 for use in adult patients with acute bacterial skin and skin structure infections. The recommended dosing regimen for effective use of dalbavancin is 1,000 mg followed by a 500 mg dose after 1 week. Two multinational, identically designed, non-inferiority trials, DISCOVER 1 and 2, demonstrated similar early clinical success with dalbavancin compared to vancomycin with an option to switch to oral linezolid. In a recently published non-inferiority trial, a single-dose regimen of dalbavancin was compared to the traditional two-dose administration and was found to have a non-inferior clinical response. In the aforementioned trials, dalbavancin was well tolerated, with patients experiencing transient adverse events of mild to moderate severity. The prolonged half-life, excellent skin and soft tissue penetration, bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and convenient dosing make dalbavancin a reasonable option for the treatment of acute bacterial skin and skin structure infections in adult patients who have tried and failed other therapies.

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          Most cited references 32

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          Once-weekly dalbavancin versus daily conventional therapy for skin infection.

          Dalbavancin, a lipoglycopeptide antibiotic agent that is active against gram-positive pathogens, has a long plasma half-life, allowing for once-weekly dosing. DISCOVER 1 and DISCOVER 2 were identically designed noninferiority trials of dalbavancin for the treatment of acute bacterial skin and skin-structure infection.
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            Methicillin-resistant Staphylococcus aureus therapy: past, present, and future.

            Methicillin-resistant Staphylococcus aureus (MRSA) continues to be associated with significant morbidity and mortality. Vancomycin was the "gold standard" of treatment for serious MRSA infections; however, the emergence of less-susceptible strains, poor clinical outcomes, and increased nephrotoxicity with high-dose therapy are challenging its current role as first-line therapy. Linezolid is recommended for PO or IV treatment of skin and skin structure infections (SSSIs) and pneumonia caused by MRSA. Daptomycin (IV) should be considered in patients with MRSA bacteremia and right-sided endocarditis as well as in complicated SSSIs, but should not be used to treat MRSA pneumonia. Tigecycline and telavancin are alternative (IV) treatments for SSSIs caused by MRSA; however, safety concerns have limited use of these agents. Ceftaroline is the newest of the approved parenteral agents for SSSIs caused by MRSA. Several investigational agents with activity against drug-resistant gram-positive pathogens are being developed primarily for treatment of MRSA infections, including tedizolid, dalbavancin, and oritavancin.
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              The rationale for revising the Clinical and Laboratory Standards Institute vancomycin minimal inhibitory concentration interpretive criteria for Staphylococcus aureus.

              The Clinical and Laboratory Standards Institute (formerly, the NCCLS) established the susceptibility and resistance breakpoints for minimal inhibitory concentration (MIC) and disk diffusion testing of vancomycin against isolates of Staphylococcus aureus > 20 years ago. The disk diffusion breakpoints were modified in 1998 when it was recognized that vancomycin-intermediate S. aureus strains were not detected by this method. In 2006, the vancomycin MIC breakpoints for S. aureus were lowered (from or = 32 microg/mL to > or = 16 microg/mL for "resistant") to increase detection of heterogeneously resistant isolates of S. aureus. This decision reflected a growing amount of microbiological and clinical data indicating that isolates of S. aureus are less likely to respond to vancomycin therapy when the vancomycin MICs are > or = 4 microg/mL.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2016
                16 February 2016
                : 12
                : 225-232
                Affiliations
                Department of Pharmacy, Froedtert & the Medical College of Wisconsin, Milwaukee, WI, USA
                Author notes
                Correspondence: Janelle Juul, Department of Pharmacy, Froedtert & the Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, WI 53226, USA, Email janelle.juul@ 123456froedtert.com
                Article
                tcrm-12-225
                10.2147/TCRM.S71855
                4762434
                26937194
                © 2016 Juul et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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