title: High-level resistance to gentamicin in clinical isolates of Streptococcus (Enterococcus) faecium.
abstract: During a 14-month period beginning in July 1986, three distinct clinical isolates of Streptococcus (Enterococcus) faecium demonstrating high-level resistance (MIC, greater than 2,000 micrograms/ml) to gentamicin, kanamycin, tobramycin, and streptomycin were recovered from individual patients at one institution. Combinations of ampicillin with any of these agents failed to show bactericidal synergism. By filter-mating techniques, high-level gentamicin resistance could be transferred into a susceptible recipient of the same species at frequencies as high as 1 x 10(-4); transfer into Streptococcus faecalis JH2-7 occurred at lower frequencies (less than 2 x 10(-7). Aminoglycoside substrate profile analysis of clinical isolates as well as of laboratory-derived cured strains and transconjugants revealed 2"-aminoglycoside phosphotransferase and 3'-aminoglycoside phosphotransferase (III) phosphorylating enzymes, AAC-6' acetylating activity above that attributable to the intrinsic activity characteristic of S. faecium, and a streptomycin adenylylating enzyme. All three isolates carried a 51-megadalton plasmid. Curing of this plasmid or conjugative transfer into susceptible recipients was associated with the loss or acquisition of high-level gentamicin resistance, respectively. Loss of high-level gentamicin resistance was also observed when curing techniques resulted in a decrease in the size of this plasmid equivalent to a 10-megadalton deletion. Transferable, high-level resistance to gentamicin and other aminoglycosides, which was previously recognized in S. faecalis, has now emerged in clinical isolates of S. faecium, with the attendant concerns for possible spread.
authors.affiliation: Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts.
authors.forename: G M
authors.initials: GM
authors.lastname: Eliopoulos
authors.forename: C
authors.initials: C
authors.lastname: Wennersten
authors.forename: S
authors.initials: S
authors.lastname: Zighelboim-Daum
authors.forename: E
authors.initials: E
authors.lastname: Reiszner
authors.forename: D
authors.initials: D
authors.lastname: Goldmann
authors.forename: R C
authors.initials: RC
authors.lastname: Moellering
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000235:genetics; D005839:Gentamicins / Q000494:pharmacology*; D010770:Phosphotransferases / Q000378:metabolism; D010957:Plasmids / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D000667:Ampicillin; D010770:Phosphotransferases