Rijksinstituut voor Volksgezondheid en Milieu (National Institute for Public Health and the Environment, RIVM), Bilthoven, the Netherlands, on behalf of all EARSS participants
For the past seven years (1999 to 2006), the European Antimicrobial Resistance Surveillance System (EARSS, http://www.earss.rivm.nl
) has collected antimicrobial susceptibility test results of invasive isolates in humans of seven bacterial species that serve as indicators for the development of antimicrobial resistance in Europe. The species are Streptococcus pneumoniae
, Staphylococcus aureus
, Escherichia coli
, Enterococcus faecalis
, Enterococcus faecium
, Klebsiella pneumoniae
and Pseudomonas aeruginosa
. Routine data for these pathogens are now regularly submitted by over 900 laboratories serving around 1400 hospitals in 32 European countries. Based on a previous laboratory/hospital questionnaire, the overall hospital catchment population of the EARSS network is estimated to include over 100 million inhabitants in the European region, with national coverage rates that range between 20 and 100% for individual countries.
For S. aureus, 12 countries out of 29 with low, medium and high baseline MRSA endemicity reported a significant increase in the proportion of MRSA within the last seven years. At the same time, it appears that the MRSA pandemic is not an irreversible secular trend, as two European countries (Slovenia and France) succeeded in constantly reducing the proportion of MRSA among S. aureus blood stream infections over the last five or six years through rigorously implementing containment programs.
Figure 1. Staphylococcus aureus: trends of methicillin-resistance by country, 1999-2005. Only the countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends.
The proportion of antibiotic-resistant S. pneumoniae continues to change, with a marked increase of erythromycin resistance in most countries, decreasing penicillin resistance in some highly endemic countries and an increase in penicillin resistance in some low endemic countries. The resistance is mainly confined to few serogroups, all of which are covered by the currently promoted conjugate vaccines. This suggests that vaccination, especially in young children, may represent an effective additional means of controlling antibiotic resistance in pneumococcal disease in Europe.
The Europe-wide increase of resistance of E. coli to all antimicrobial classes recorded by EARSS is a disturbing development that has a seemingly inexorable vigor. The highest resistance proportions have been reported for aminopenicillins ranging between 26% and 77%. The speed with which fluoroquinolones lose their activity against E. coli is unparalleled in the EARSS database, as 25 out of 28 countries showed a clear increase in fluoroquinolone resistance (2001-2005). Combined resistance is a frequent occurrence, with co-resistance to four antimicrobial classes, including third-generation cephalosporins, already among the four most common resistance patterns encountered in invasive E. coli in Europe, and these resistance traits are also on the increase.
Figure 2. Escherichia coli: trends of multi-resistance* by country, 2001-2005. Only the countries that reported 20 isolates or more per year for at least 3 years were included. The arrows indicate significant trends.
*Combined resistance to fluoroquinolones, third-generation cephalosporins and aminoglycosides.
With the ongoing spread of the hospital adapted clonal complex 17, a virulent genetic subpopulation of E. faecium, in Europe, outbreaks of vancomycin-resistant E. faecium continue to afflict hospitals in various countries. The spread of these hospital-adapted strains occurs against a background of high-level aminoglycoside resistance.
Since July 2005, EARSS has also collected data on K. pneumoniae and P. aeruginosa. In K. pneumoniae, a high prevalence of resistant strains to third-generation cephalosporins, fluoroquinolones and aminoglycosides or a combination of all three antimicrobial groups has been observed in eastern and south-eastern Europe. The most frequent multi-resistant phenotype shows resistance to all three antimicrobial classes recorded by EARSS. Combined resistance is the dominant threat imposed by invasive P. aeruginosa in Europe. Since resistance in P. aeruginosa emerges readily during antibiotic treatment, the time at which blood cultures are taken is crucial. Assuming the diagnostic habits in Europe are comparable, our data suggest that the same geographical gradient observed for all other Gram-negative pathogens, namely lower resistance in the north-west and increasing resistance towards the south-east, also holds for P. aeruginosa.
It appears that the overall threat imposed on European countries by the increasing loss of antimicrobial effectiveness continues with the same speed as has been previously described by our network. This is shown most convincingly among the pathogens that are frequently transmitted in healthcare settings (MRSA and VRE) and for antimicrobial compounds that are available for oral administration and hence preferred in ambulatory care (aminopenicillins, macrolides, and fluoroquinolones). The growing availability of third-line antimicrobial drugs as oral formulations is, in this context, a matter of concern and underscores the need of locally or nationally advised prescribing practices for both ambulatory and hospital-based care.
EARSS is also committed to improving the understanding of the spread of antimicrobial resistance by identifying the expansion of clones of particular public health importance through common typing approaches. Since 2004, EARSS has collected S. pneumoniae serotype data next to the antimicrobial susceptibility testing results. Ten countries have now made serotype data available for this species. Starting in 2006, EARSS has dedicated itself to identifying the most dominant S. aureus strains causing invasive infections in the European region by spa-typing. This is the most promising typing technique in terms of ease, costs, discriminatory ability and the availability of user-friendly software and a central database. The SeqNet.org initiative (http://www.seqnet.org) established and maintains this database at http://www.ridom.de/spaserver, where information of spa types, like their frequencies, their relation to MLST sequence types and epidemiological information is freely available. The first results are expected before the end of 2007.
EARSS is an international initiative funded by the European Centre for Disease Prevention and Control (ECDC) and the Netherlands’ Ministerie voor Volksgezondheid, Welzijn en Sport (Ministry of Health, Welfare and Sports, VWS). It maintains a comprehensive surveillance and information system that links national networks and provides comparable and validated data on the prevalence and spread of seven major invasive bacteria with clinically and epidemiologically relevant antimicrobial resistance in Europe.