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