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History and evolution of antibiotic resistance in coagulase-negative staphylococci: Susceptibility profiles of new anti-staphylococcal agents

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      Abstract

      Coagulase-negative staphylococci (CNS) are a heterogenous group of Gram-positive cocci that are widespread commensals among mammalia. Unlike their coagulase-positive counterpart, Staphylococcus aureus, CNS produce few virulence patterns and normally refrain from invading tissue. Yet, not only can CNS cause infections in normal host tissue, but modern medicine has also seen their rise as opportunists that display adherence to medical device materials to produce a protective biofilm. CNS have historically been more resistant to antimicrobials, including the β-lactam antibiotics, than S. aureus and some hospitals reveal rates of oxacillin resistance in CNS approaching 90%. Cross resistance to non-β-lactam agents has been a recurrent theme over the past 40 years in the CNS. Thus, there has been a pressing need for newer antimicrobial agents with good antistaphylococcal activity. Those new agents tend to have excellent antistaphylococcal activity include daptomycin, linezolid, oritavancin, telavancin, tigecycline, dalbavancin, new quinolones, and ceftibiprole, several of which have unique mechanisms of action. The MIC 90 for these new compounds typically ranges from 0.5–4 μg/mL. Staphylococcal biofilm formation is quite common in CNS infections and markedly increases the MIC for most older antimicrobials. Several of the newer agents offer some promise of penetration of biofilm to inhibit or kill adherent staphylococci. CNS will likely remain a major cause of infections in the modern age, evolve further antimicrobial resistance mechanisms, and require development of newer antimicrobials for curative therapy.

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      Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999.

       Linda J. Bell,  ,  D Diekema (2001)
      Between January 1997 and December 1999, bloodstream isolates from 15,439 patients infected with Staphylococcus aureus and 6350 patients infected with coagulase-negative Staphylococcus species (CoNS) were referred by SENTRY-participating hospitals in the United States, Canada, Latin America, Europe, and the Western Pacific region. S. aureus was found to be the most prevalent cause of bloodstream infection, skin and soft-tissue infection, and pneumonia in almost all geographic areas. A notable increase in methicillin (oxacillin) resistance among community-onset and hospital-acquired S. aureus strains was observed in the US centers. The prevalence of methicillin (oxacillin)-resistant S. aureus varied greatly by region, site of infection, and whether the infection was nosocomial or community onset. Rates of methicillin resistance were extremely high among S. aureus isolates from centers in Hong Kong and Japan. Uniformly high levels of methicillin resistance were observed among CoNS isolates. Given the increasing multidrug resistance among staphylococci and the possible emergence of vancomycin-resistant strains, global strategies are needed to control emergence and spread of multiply resistant staphylococci.
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        Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.

        Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
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          Pathogenesis of infections due to coagulase-negative staphylococci.

          As a group, the coagulase-negative staphylococci (CoNS) are among the most frequently isolated bacteria in the clinical microbiology laboratory and are becoming increasingly important, especially as causes of hospital-acquired infections. These bacteria are normal inhabitants of human skin and mucous membranes and, therefore, one of the major challenges of daily diagnostic work is to distinguish clinically significant CoNS from contaminant strains. This overview addresses current knowledge of the pathogenesis of infections due to CoNS and particularly focuses on virulence factors of the species Staphylococcus epidermidis. S epidermidis has been identified as a major cause of nosocomial infections, especially in patients with predisposing factors such as indwelling or implanted foreign polymer bodies. Most important in the pathogenesis of foreign-body-associated infections is the ability of these bacteria to colonise the polymer surface by the formation of a thick, multilayered biofilm. Biofilm formation takes place in two phases. The first phase involves the attachment of the bacteria to polymer surfaces that may be either unmodified or coated with host extracellular matrix proteins. In the second phase, the bacteria proliferate and accumulate into multilayered cell clusters that are embedded in an extracellular material. The bacterial factors involved in both phases of biofilm formation are discussed in this review. In addition, the most important aspects of the pathogenic potential of S saprophyticus, S lugdunensis, and S schleiferi are described, although, compared with S epidermidis, much less is known in these species concerning their virulence factors.
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            Author and article information

            Affiliations
            [1 ]simpleRalph H. Johnson Department of Veterans Affairs Medical Center Charleston, SC, USA
            [2 ]simpleDepartment of Medicine and Microbiology and Immunology, Medical University of South Carolina Charleston, SC, USA
            Author notes
            Correspondence: Joseph F John 109 Bee Street (14), Charleston, SC 29401, USA Tel +1 843 789 7942 Email joseph.john2@ 123456va.gov
            Journal
            Ther Clin Risk Manag
            Therapeutics and Clinical Risk Management
            Therapeutics and Clinical Risk Management
            Dove Medical Press
            1176-6336
            1178-203X
            December 2007
            December 2007
            : 3
            : 6
            : 1143-1152
            2387300
            18516271
            © 2007 Dove Medical Press Limited. All rights reserved
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