GLYCOPEPTIDE-RESISTANT ENTEROCOCCI - A DECADE OF EXPERIENCE

Since their first description in 1988, glycopeptide-resistant enteroco cci (GRE) have emerged as a significant cause of nosocomial infections and colonisations, particularly in Europe and the USA. Two major gene tically distinct forms of acquired resistance, designated VanA and Van B, are recognised, although intrinsic resistance occurs in some entero coccal species (VanC) and a third form of acquired resistance (VanD) h as been reported recently. The biochemical basis of each resistance me chanism is similar; the resistant enterococci produce modified peptido glycan precursors that show decreased binding affinity for glycopeptid e antibiotics. Although VanA resistance is detected readily in the cli nical laboratory, the variable levels of vancomycin resistance associa ted with the other phenotypes makes detection less reliable. Under-rep orting of VanB resistance as a result of a lower detection rate may ac count, in part, for the difference in the numbers of enterococci displ aying VanA and VanB resistance referred to the PHLS Laboratory of Hosp ital Infection. Since 1987, GRE have been referred from >1100 patients in almost 100 hospitals, but 88% of these isolates displayed the VanA phenotype. It is possible that, in addition to the problems of detect ion, there may be a real difference in the prevalence of VanA and VanB resistance reflecting different epidemiologies. Our present understan ding of the genetic and biochemical basis of these acquired forms of g lycopeptide resistance has been gained mainly in the last 5 years. How ever, these relatively new enterococcal resistances appear still to be evolving; there have now been reports of transferable VanB resistance associated with either large chromosomally borne transposons or plasm ids, genetic linkage of glycopeptide resistance and genes conferring h igh-level resistance to aminoglycoside antibiotics, epidemic strains o f glycopeptide-resistant Enterococcus faecium isolated from multiple p atients in numerous hospitals, and of glycopeptide dependence (mutant enterococci that actually require these agents for growth). The gene c lusters responsible for VanA and VanB resistance are located on transp osable elements, and both transposition and plasmid transfer have resu lted in the dissemination of these resistance genes into diverse strai ns of several species of enterococci. Despite extensive research, know ledge of the origins of these resistances remains poor. There is littl e homology between the resistance genes and DNA from either intrinsica lly resistant gram-positive genera or from the soil bacteria that prod uce glycopeptides, which argues against direct transfer to enterococci from these sources. However, recent data suggest a more distant, evol utionary relationship with genes found in glycopeptide-producing bacte ria. In Europe, VanA resistance occurs in enterococci isolated in the community, from sewage, animal faeces and raw meat. This reservoir sug gests that VanA may not have evolved in hospitals, and its existence h as been attributed, controversially, to use of the glycopeptide avopar cin as a growth promoter, especially in pigs and poultry. However, as avoparcin has never been licensed for use in the USA and, to date, Van B resistance has not been confirmed in non-human enterococci, it is cl ear that the epidemiology of acquired glycopeptide resistance in enter ococci is complex, with many factors contributing to its evolution and global dissemination.