Eurosurveillance - Volume 13, Issue 47, 20 November 2008

Antimicrobial resistance due to the continuous selective pressure from widespread use of antimicrobials in humans, animals and agriculture has been a growing problem for decades. In 2001, European Union Ministers of Health adopted Council Recommendations on the prudent use of antimicrobial agents in human medicine. This issue of Eurosurveillance is the second one this month dedicated to antimicrobial resistance, in connection with the first-ever European Antibiotic Awareness Day - a European Union (EU) health initiative involving all key players to increase awareness of Europeans about antimicrobial resistance and prudent use of antibiotics.

We describe the implementation of an enhanced surveillance pilot for newly acquired hepatitis C (HCV) in men who have sex with men (MSM) in London and the South East region of England. Preliminary findings suggest ongoing HCV transmission among MSM infected with human immunodeficiency virus (HIV) and that enhanced surveillance for newly acquired HCV in MSM is feasible.

Vancomycin-resistant enterococci (VRE) first appeared in the late 1980s in a few European countries. Nowadays, six types of acquired vancomycin resistance in enterococci are known; however, only VanA and to a lesser extent VanB are widely prevalent. Various genes encode acquired vancomycin resistance and these are typically associated with mobile genetic elements which allow resistance to spread clonally and laterally. The major reservoir of acquired vancomycin resistance is Enterococcus faecium; vancomycin-resistant Enterococcus faecalis are still rare. Population analysis of E. faecium has revealed a distinct subpopulation of hospital-acquired strain types, which can be differentiated by molecular typing methods (MLVA, MLST) from human commensal and animal strains. Hospital-acquired E. faecium have additional genomic content (accessory genome) including several factors known or supposed to be virulence-associated. Acquired ampicillin resistance is a major phenotypic marker of hospital-acquired E. faecium in Europe and experience has shown that it often precedes increasing rates of VRE with a delay of several years. Several factors are known to promote VRE colonisation and transmission; however, despite having populations with similar predispositions and preconditions, rates of VRE vary all over Europe.

Extended-spectrum beta-lactamases (ESBLs) have been increasingly reported in Europe since their first description in 1983. During the 1990s, they were described mainly as members of the TEM- and SHV-beta-lactamase families in Klebsiella pneumoniae causing nosocomial outbreaks. Nowadays, they are mostly found in Escherichia coli that cause community-acquired infections and with increasing frequency contain CTX-M enzymes. Dissemination of specific clones or clonal groups and epidemic plasmids in community and nosocomial settings has been the main reason for the increase in most of the widespread ESBLs belonging to the TEM (TEM-24, TEM-4, TEM-52), SHV (SHV-5, SHV-12) and CTX-M (CTX-M-9, CTX-M-3, CTX-M-14 or CTX-M-15) families in Europe. Co-selection with other resistances, especially to fluoroquinolones, aminoglycosides and sulfonamides, seems to have contributed to the problem. The emergence of epidemic clones harbouring several beta-lactamases simultaneously (ESBLs, metallo-beta-lactamases or cephamycinases) and of new mechanisms of resistance to fluoroquinolones and aminoglycosides warrants future surveillance studies.

International and local surveillance networks as well as numerous reports in the biomedical literature provide evidence that the prevalence of antibiotic resistant Gram-negative bacteria is escalating in many European countries. Furthermore, isolates characterised as multidrug-resistant (i.e. resistant to three or more classes of antimicrobials), extensively drug resistant (i.e. resistant to all but one or two classes) or pandrug-resistant (i.e. resistant to all available classes) are increasingly frequently isolated in hospitalised patients causing infections for which no adequate therapeutic options exist. Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae are specifically addressed in this review as the most problematic and often extensively or pandrug-resistant pathogens. According to the available multicentre surveillance studies, the proportion of imipenem-resistant A. baumannii strains is reported to be as high as 85% in bloodstream isolates from intensive care unit patients in Greece and 48% in clinical isolates from hospitalised patients in Spain and Turkey. Among 33 European countries participating in the European Antimicrobial Resistance Surveillance System (EARSS) in 2007, six countries reported carbapenem resistance rates of more than 25% among P. aeruginosa isolates, the highest rate reported from Greece (51%). According to EARSS, Greece has also the highest resistance rates among K. pneumoniae; 46% to carbapenems, 58% to quinolones and 63% to third generation cephalosporins. This review describes the magnitude of antimicrobial resistance in Gram-negative bacteria in Europe highlighting where the efforts of the scientific communities, the academia, the industry and the government should focus in order to confront this threat.