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      Therapeutics and Clinical Risk Management (submit here)

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      Tigecycline in the treatment of complicated intra-abdominal and complicated skin and skin structure infections


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          Tigecycline, a glycylcycline related to the tetracycline class of antibiotics, represents a new option for the treatment of complicated intra-abdominal and complicated skin and skin structure infections. It displays favorable activity in vitro against the most common causative Gram-positive, Gram-negative and anaerobic pathogens. In addition, tigecycline demonstrates activity against drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and organisms (such as Escherichia coli and Klebsiella pneumoniae) producing extended-spectrum beta-lactamases. Tigecycline lacks activity in vitro against Pseudomonas and Proteus spp. In randomized clinical trials, tigecycline administered intravenously twice daily has demonstrated efficacy similar to comparators for a variety of complicated skin and skin structure and complicated intra-abdominal infections. The potential for significant drug interactions with tigecycline appears to be minimal. Dosing adjustment is needed for patients with severe hepatic impairment. The predominant side effect associated with its use to date has been gastrointestinal intolerance (nausea and vomiting).

          Most cited references137

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          Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance.

          Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.
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            Practice guidelines for the diagnosis and management of skin and soft-tissue infections.

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              Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

              The morbidity and cost for cure associated with skin and soft tissue infections (SSTIs) have recently become more complicated because of the increasing prevalence of multidrug-resistant pathogens associated with this healthcare problem. The SENTRY Antimicrobial Surveillance Program has been monitoring SSTI since 1997, and now presents data from 3 continents over a 7-year period (1998-2004). Isolates were tested by reference broth microdilution methods at a central laboratory using the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) methods and interpretative criteria. The predominant pathogens included Staphylococcus aureus (ranked 1st in all geographic regions), Pseudomonas aeruginosa, Escherichia coli, and Enterococcus spp. A considerable variation in the methicillin (oxacillin)-resistant S. aureus rate was noted between countries and continents, with the overall rate highest in North America (35.9%) compared with Latin America (29.4%) and Europe (22.8%). Vancomycin-resistant Enterococcus spp. increased in Europe (4.1%) and North America (6.2%) during the period, but remained low and relatively unchanged in Latin America. Among the P. aeruginosa isolates tested, susceptibility to imipenem was much lower in Latin America (65.3%) compared with the other regions (80.7-88.7%), and resistance being associated with an increase in metallo-beta-lactamase-producing strains in Latin America and in some European countries. Multidrug-resistant strains of P. aeruginosa were also more of a concern in Latin America (24.7%) compared with Europe (10.8%) or North America (3.2%). Latin America also had the highest occurrence of extended-spectrum beta-lactamase-producing isolates among E. coli (15.1%) and Klebsiella spp. (48.0%) when compared with other regions. Continued surveillance of pathogen prevalence and antimicrobial resistance patterns should provide information that is important to improve empiric care particularly in the hospital environment.

                Author and article information

                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                December 2007
                December 2007
                : 3
                : 6
                : 1059-1070
                [1 ]Campbell University School of Pharmacy Buies Creek, NC, USA
                [2 ]Duke University Medical Center Durham, NC, USA
                [3 ]Duke University School of Medicine Durham, NC, USA
                Author notes
                Correspondence: Mary L Townsend PO Box 1090, Buies Creek, NC 27506, USA Tel 919 286 0411 ext 7796 Fax 919 286 6987 Email townsend@ 123456mailcenter.campbell.edu
                © 2007 Dove Medical Press Limited. All rights reserved

                complicated skin and skin structure infections,tigecycline,intra-abdominal infections


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