Impact of LY146032 on Streptococcus (Enterococcus) faecalis translocation in mice

The susceptibility of Swiss White mice to colonization with Streptococcus (Enterococcus) faecalis was greatly increased when the animals were given 5 mg of streptomycin sulfate per ml in their drinking water. One week after initiation of streptomycin treatment, the mice were challenged orogastrically with graded doses of streptomycin-resistant S. faecalis. The number of S. faecalis cells required to implant the intestinal tract of 50% of untreated mice was 2.9 X 10(9), but was only 4.8 X 10(3) for streptomycin-treated animals. When both groups of mice were challenged orogastrically with 4.6 X 10(6) viable S. faecalis cells, the cecum and small intestine of 100% of the streptomycin-treated animals, but only 10% of the untreated animals, were colonized with the organism. Similarly, translocation of S. faecalis to extraintestinal sites occurred in a majority of streptomycin-treated mice, but in only a small number of untreated mice. Subcutaneous administration of the experimental antibiotic LY146032 (Eli Lilly & Co., Indianapolis, Ind.) to streptomycin-treated mice concomitant with orogastric challenge with 5.5 X 10(5) viable S. faecalis cells resulted in a significant decrease in the incidence of intestinal colonization by the organism, a significant reduction in S. faecalis populations, and the absence of the organism in the liver, spleen, and heart. However, once intestinal colonization had occurred and extraintestinal infections were established, LY146032 did not significantly reduce S. faecalis populations or ameliorate the infections. We conclude that LY146032 effectively prevents translocation of S. faecalis from the intestinal tract of mice but does not resolve established extraintestinal infections.