Colonization with vancomycin-resistant Enterococcus faecium (VREF) is strongly associated with previous antimicrobial therapy, The gastrointestinal (GI) tract appears to be the major reservoir for this organism, We used antibiotic-treated Swiss Webster mice to study GI tract colonization with a characterized strain of VREF (E. faecium 228), Mice were pretreated with antibiotics in their daily drinking water and inoculated with 10(9) colony-forming units (CFU) of E. faecium 228 by oral gavage, We were able to establish persistent colonization with high concentrations of E. faecium 228 (> 8.0 log(10) CFU/g of feces) in animals treated with 5 mg/ml of streptomycin plus 1 mg/ml of cefotetan, RP 59500, a streptogramin antibiotic with good in vitro activity against VREF, was administered orally in mice (n = 8) colonized with E. faecium 228, After 14 days of treatment VREF was undetectable in feces of all treated mice (< 3.0 CFU/g), Seven days after discontinuation of RP 59500, VREF was present in the feces of all animals, VREF isolates recovered after treatment remained susceptible to RP 59500, Attempts to eradicate E. faecium 228 colonization by oral administration of a vancomycin-sensitive E. faecium strain (SF68) or Lactobacillus spp. were unsuccessful as long as animals continued to receive streptomycin and cefotetan, Recovery of E. faecium 228 from cultures of livers and gallbladders in some animals with persistent GI tract colonization suggests that the organisms may also colonize the hepatobiliary system.