A comparative evaluation of daptomycin and eight other antimicrobial agents was performed by the agar dilution technique with 56 strains of vancomycin-resistant gram-positive bacteria, including Leuconostoc, Lactobacillus, and Pediococcus spp. Erythromycin, daptomycin, clindamycin, and gentamicin exhibited the greatest activities, whereas penicillin, ampicillin, and cefotaxime showed moderate activities. The organisms were all highly resistant to vancomycin and cefoxitin.Although still uncommon, severe infections due to vancomycin-resistant (V-R) gram-positive bacteria belonging to the genera Leuconostoc (3,[5][6][7]10,13), Lactobacilllus (12), and Pediococcus (4) have recently been reported. Because of this and the relative lack of information in the literature concerning antibiotic susceptibilities and methods for their determination, we undertook the study reported here, which is a comparative evaluation of the activities of daptomycin and eight antimicrobial agents against V-R gram-positive bacteria. Daptomycin (LY146032), a lipopeptide antibiotic derived from a fermentation product, exhibits a high degree of in vitro activity against gram-positive bacteria by inhibiting cell wall peptidoglycan biosynthesis (1).The bacteria used in this study were 56 V-R gram-positive strains belonging to the genera Leuconostoc (n = 13), Lactobacillus (n = 32), or Pediococcus (n = 6) or were strains of indeterminate genus (n = 5). Forty-six strains had been isolated from clinical specimens at Massachusetts General Hospital (11) incubation at 35°C in a 5 to 7% CO2 atmosphere, since some strains exhibited poor growth in an ambient atmosphere. For all strains, lactobacillus Mann, Rogosa, and Sharpe (MRS) broth (Difco Laboratories, Detroit, Mich.) was used to achieve the active growing phase, and the final inoculum dilutions were performed in sterile deionized water.Susceptibilities of the V-R isolates to the agents tested in this study are shown in Tables 1 and 2. All of the organisms were highly resistant to vancomycin and cefoxitin. In contrast, erythromycin, clindamycin, and gentamicin were quite active, with more than 90% of the strains being susceptible Leuconostoc (