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      Hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) in Italy

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          Abstract

          The aim of our study was to trace the dynamic changes of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) lineages in Italy, comparing the genotypic backgrounds of contemporary isolates over a period of 17 years, with those of a sample of early MRSA strains from 1980.

          In total, 301 non-repetitive MRSA clinical isolates, recovered from 19 Italian hospitals between 1990 and 2007 were selected and analyzed for their antibiotic resistance, typed by PFGE and SCC mec, grouped into clonal-types and further characterized using Multi Locus Sequence Typing (MLST). A sample of fifteen early MRSA strains from 1980 was also used for comparison.

          The most interesting feature was the recent increase of ST228-MRSA-I (formerly the Italian clone; PFGE E) over the period 2000–2007 (57%), when compared to the period 1990–1999 (29%), and its stability to date, associated with a decrease of the highly epidemic ST247-MRSA-IA (formerly the Iberian clone; PFGE A), (23% from 1990 to 1999, 6% from 2000 to 2007). ST1-MRSA-I (1 out of 2 strains carrying ccrA 2B 2), ST8-MRSA-I (4 strains), ST15-MRSA-I (1 out of 4 carrying ccrA 2B 2) and ST30-MRSA-I (2 out of 5 carrying no ccrAB-types and ccrC) were the predominant earliest STs among the MRSA strains in 1980.

          A temporal shift in the susceptibility levels to glycopeptides was observed: strains with vancomycin MIC of ≥ 2 mg/L increased from 19.4% to 35.5%.

          In conclusion, we describe the alternation of MRSA clones that occurred in hospitals from 1990 to 2007 and the increase of the glycopeptide MIC levels, reflecting a worldwide trend. We document the detection of ST1, ST8, ST15 and ST30 in the 1980 isolates; we hypothesize their possible latency and their appearance as the current CA-MRSA clones.

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          eBURST: inferring patterns of evolutionary descent among clusters of related bacterial genotypes from multilocus sequence typing data.

          The introduction of multilocus sequence typing (MLST) for the precise characterization of isolates of bacterial pathogens has had a marked impact on both routine epidemiological surveillance and microbial population biology. In both fields, a key prerequisite for exploiting this resource is the ability to discern the relatedness and patterns of evolutionary descent among isolates with similar genotypes. Traditional clustering techniques, such as dendrograms, provide a very poor representation of recent evolutionary events, as they attempt to reconstruct relationships in the absence of a realistic model of the way in which bacterial clones emerge and diversify to form clonal complexes. An increasingly popular approach, called BURST, has been used as an alternative, but present implementations are unable to cope with very large data sets and offer crude graphical outputs. Here we present a new implementation of this algorithm, eBURST, which divides an MLST data set of any size into groups of related isolates and clonal complexes, predicts the founding (ancestral) genotype of each clonal complex, and computes the bootstrap support for the assignment. The most parsimonious patterns of descent of all isolates in each clonal complex from the predicted founder(s) are then displayed. The advantages of eBURST for exploring patterns of evolutionary descent are demonstrated with a number of examples, including the simple Spain(23F)-1 clonal complex of Streptococcus pneumoniae, "population snapshots" of the entire S. pneumoniae and Staphylococcus aureus MLST databases, and the more complicated clonal complexes observed for Campylobacter jejuni and Neisseria meningitidis.
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            The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA).

            Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. The evolutionary origins of MRSA are poorly understood, no rational nomenclature exists, and there is no consensus on the number of major MRSA clones or the relatedness of clones described from different countries. We resolve all of these issues and provide a more thorough and precise analysis of the evolution of MRSA clones than has previously been possible. Using multilocus sequence typing and an algorithm, BURST, we analyzed an international collection of 912 MRSA and methicillin-susceptible S. aureus (MSSA) isolates. We identified 11 major MRSA clones within five groups of related genotypes. The putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor were inferred by using BURST, which, together with analysis of the methicillin resistance genes, established the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSA clone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methicillin resistance genes. Major MRSA clones have arisen repeatedly from successful epidemic MSSA strains, and isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes.
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              Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia.

              Vancomycin treatment failure in methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not uncommon, even when MRSA is susceptible to vancomycin. The aim of our study was to evaluate whether vancomycin minimum inhibitory concentration has any influence on the mortality associated with MRSA bacteremia. A total of 414 episodes of MRSA bacteremia were prospectively followed-up from 1991 through 2005. MIC of vancomycin for the first isolate was determined by E-test. Clinical variables recorded were age, comorbidity, prior administration of vancomycin, use of corticosteroids, prognosis of underlying disease, source of bacteremia, the need for mechanical ventilation, shock, and mortality. A "treatment group" variable was created and defined as follows: (1) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1 microg/mL (38 episodes), (2) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 1.5 microg/mL (90 episodes), (3) receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (40 episodes), and (4) receipt of inappropriate empirical therapy (246 episodes). Univariate and multivariate analyses were performed. Episodes caused by strains with a vancomycin MIC of 2 microg/mL were independently associated with a lower risk of shock (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.15-0.75). Multivariate analysis selected receipt of empirical vancomycin and an isolate with a vancomycin MIC of 2 microg/mL (OR, 6.39; 95% CI, 1.68-24.3), receipt of inappropriate empirical therapy (OR, 3.62; 95% CI, 1.20-10.9), increasing age (OR, 1.02; 95% CI, 1.00-1.04), use of corticosteroids (OR, 1.85; 95% CI, 1.04-3.29), an ultimately (OR, 10.2; 95% CI, 2.85-36.8) or rapidly (OR, 1.81; 95% CI, 1.06-3.10) fatal underlying disease, high-risk (OR, 3.60; 95% CI, 1.89-6.88) and intermediate-risk (OR, 2.18; 95% CI, 1.17-4.04) sources of bacteremia, and shock (OR, 7.38; 95% CI, 4.11-13.3) as the best predictors of mortality. Mortality associated with MRSA bacteremia was significantly higher when the empirical antibiotic was inappropriate and when vancomycin was empirically used for treatment of infection with strains with a high vancomycin MIC (>1 microg/mL).
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                Author and article information

                Journal
                Ann Clin Microbiol Antimicrob
                Annals of Clinical Microbiology and Antimicrobials
                BioMed Central
                1476-0711
                2009
                24 June 2009
                : 8
                : 22
                Affiliations
                [1 ]Department of Microbiology, University of Catania, Italy
                Article
                1476-0711-8-22
                10.1186/1476-0711-8-22
                2708121
                19552801
                16816846-af3e-44c9-97c5-214222336e51
                Copyright © 2009 Campanile et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 March 2009
                : 24 June 2009
                Categories
                Research

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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