Team:SDU-Denmark/Background

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For now: this is from http://www.rivm.nl/earss/Images/EARSS%202007_FINAL_tcm61-55933.pdf
For now: this is from http://www.rivm.nl/earss/Images/EARSS%202007_FINAL_tcm61-55933.pdf
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=Staphylococcus aureus=
 
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==Clinical and epidemiological importance==
 
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Staphylococcus aureus is a gram-positive bacterium that colonizes the skin of about 30% of healthy
 
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humans. Although mainly a harmless coloniser, S. aureus can cause severe infection. Its oxacillinresistant
 
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form (methicillin-resistant S. aureus, MRSA) is the most important cause of antibioticresistant
 
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health care-associated infections worldwide (26). Since health care-associated MRSA
 
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infections add to the number of infections caused by methicillin-susceptible S. aureus, a high incidence
 
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of MRSA adds to the overall burden of infections caused by this species in hospitals (20). Moreover,
 
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infections with MRSA may result in prolonged hospital stay and in higher mortality rates (7), owing
 
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mainly to the increased toxicity and limited effectiveness of alternative treatment regimens. MRSA
 
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is currently the most commonly identified antibiotic-resistant pathogen in hospitals in many parts of
 
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the world, including Europe, the Americas, North Africa and the Middle- and Far-East.
 
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==Resistance mechanisms==
 
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S. aureus acquires resistance to methicillin and all other beta-lactam antibiotics through expression
 
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of the exogenous mecA gene, that codes for a variant penicillin binding protein PBP2’ (PBP2a) with
 
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low affinity to beta-lactams, (21), thus preventing the drug induced inhibition of cell wall synthesis.
 
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The level of methicillin resistance (defined by its minimum inhibitory concentration, MIC) depends
 
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on the amount of PBP2’ production, which is influenced by various genetic factors. Resistance levels
 
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of mecA-positive strains can thus range from phenotypically susceptible to highly resistant (5). Upon
 
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challenge with methicillin, a population of a heterogeneously resistant MRSA strain may quickly be
 
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outgrown by a subpopulation of highly resistant variants.
 
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Glycopeptide antibiotics include vancomycin and teicoplanin. Both are very large molecules that
 
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through binding to the terminal amino acid residues (D-alanyl-D-alanine) of the peptide side chains
 
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in the growing peptidoglycan polymers inhibit the cross linking essential for cell wall stability. It is
 
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estimated that to block cell wall synthesis effectively, the glycopeptide antibiotic has to penetrate
 
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about 20 peptidoglycan layers, all with free D-alanyl-D-alanine targets, without being ‘trapped’,
 
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and this together with a poor penetration into infected tissues, limits the therapeutic effects of glycopeptides.
 
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Cell wall thickening of S. aureus thus increases its ability to resist vancomycin, and in S.
 
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aureus most strains with reduced vancomycin susceptibility have a markedly thicker cell wall (21).
 
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Vancomycin resistance is far more prevalent among enterococci, owing to different genetic resistance
 
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determinants.
 
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==Staphylococcus aureus resistance trends: 1999-2007==
 
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===Beta-lactams===
 
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In 2007, 31 countries reported AST results of 31,591 invasive S. aureus isolates to EARSS, of which
 
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22% (n=7,115) were identified as MRSA. At least thirty-eight percent (n=2,736) of these MRSA
 
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isolates were confirmed by oxacillin MIC, PCR mecA-gene, or PBP2A-agglutination.
 
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MRSA proportions vary from 0% in the north to over 50% in southern European countries. Thirteen
 
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countries reported MRSA proportions equal or higher than 25%. Like previous years, all Mediterranean
 
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countries, Romania, the United Kingdom and Ireland were included in this category. In the
 
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UK, yet another year of decreasing MRSA proportions turned the increasing trend that prevailed
 
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until 2006 into a decrease, although this finding was not found by the subset analysis of laboratories
 
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that consistently provided data for the entire EARSS observation period (9 years). In France, Turkey
 
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and Slovenia, the MRSA proportions are still on the decrease and for the first time in 2007 proportions
 
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in Austria, Bulgaria and Italy also showed a significant decrease (not confirmed for the subset
 
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laboratories in Austria and Italy). Significant increases reported in 2006 continued in 2007 in Czech
 
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Republic, Hungary and Germany (Figure 4.8).
 
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Four countries had MRSA proportions over 40%, of which Portugal and Malta still show a continuing
 
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increase. In Greece, like last year, the subset laboratories showed a significant decrease, which
 
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was not confirmed by the overall trend. The same holds for an increase in Spain. These differences
 
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between the total and the subset laboratories are caused by changes in the national EARSS participation
 
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over the years.
 
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In the northern part of Europe, MRSA rates are below 3%, except for the Baltic States (8%-9%). In
 
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Latvia, MRSA rates continue to decrease strongly, from 25% in 2004 to 8% in 2007. However, in the
 
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Netherlands, Finland and Denmark a significant increase was reported, although in Denmark not in
 
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the subset laboratories. The MRSA rates of Estonia, Iceland, Norway and Sweden remain relatively
 
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stable. In Belgium, the decrease of 2006 was maintained, although not (yet) reflected as statistically
 
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significant trend (Figure 4.9).
 
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===Glycopeptides/vancomycin===
 
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Overall, four confirmed VISA’s and no VRSA were reported to the EARSS database in 2007.
 
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Vancomycin intermediate resistant S. aureus were reported by France (n=1), Ireland (n=1) and The
 
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Netherlands (n=2).
 
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==MRSA by hospital department==
 
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S. aureus susceptibility data reported to EARSS originate from different hospital departments. Across
 
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the national EARSS networks, an average of 12% (min. 2%, max.26%) of the invasive S. aureus isolates
 
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was isolated from ICU patients. MRSA strains are more frequently isolated from ICU patients
 
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than non-ICU patients, and therefore country-specific differences in enrolment can be of influence on
 
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the comparability of the overall MRSA proportions.
 
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In 22 of 30 countries the MRSA proportions in ICU were higher compared to non-IC units; for twelve
 
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countries this difference was significant. In six countries, the MRSA proportions in ICU-isolates
 
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were lower than in the non-ICU isolates. Two countries had no MRSA isolates at all (Figure 4.10).
 
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In six countries, Croatia, Greece, Israel, Malta, Portugal, Turkey, the proportion of MRSA found
 
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among ICU patients was over 60%. Although in these counties, except for Malta, the MRSA proportions
 
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in ICUs were significantly higher compared to non-IC units, these high levels go together
 
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with high rates of MRSA, above 30%. However, high specialisation of ICU’s with very vulnerable
 
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patients could have been of influence.
 
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==Conclusions==
 
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MRSA is still an increasing problem all over Europe. In a number of low-endemic countries increasing
 
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MRSA proportions are found. In the high endemic countries, on the other hand, some countries seem
 

Revision as of 14:09, 23 July 2009

For now: this is from http://www.rivm.nl/earss/Images/EARSS%202007_FINAL_tcm61-55933.pdf