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Impact of LY146032 on Streptococcus (Enterococcus) faecalis translocation in mice
S H Dougherty1, D J Hentges, S W Casey
1Department of Surgery, Texas Tech University Health Sciences Center, El Paso 79905.
Abstract:
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.
Insights
Streptomycin treatment dramatically increases mice susceptibility to Streptococcus faecalis colonization. The antibiotic LY146032 prevents S. faecalis translocation from the gut but does not treat established infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Streptococcus (Enterococcus) faecalis can colonize the gastrointestinal tract.
- Antibiotic treatment can alter gut microbiota, potentially increasing pathogen susceptibility.
- Translocation of gut bacteria to extraintestinal sites is a significant clinical concern.
Purpose of the Study:
- To investigate the effect of streptomycin on S. faecalis colonization in mice.
- To evaluate the efficacy of the experimental antibiotic LY146032 in preventing and treating S. faecalis infections.
- To determine if LY146032 can prevent bacterial translocation from the gut.
Main Methods:
- Swiss White mice were treated with streptomycin sulfate in drinking water.
- Mice were orogastrically challenged with streptomycin-resistant S. faecalis.
- LY146032 was administered subcutaneously to assess its impact on colonization and translocation.
- Bacterial colonization in the intestine and translocation to extraintestinal sites (liver, spleen, heart) were quantified.
Main Results:
- Streptomycin treatment significantly increased susceptibility to S. faecalis intestinal colonization and translocation.
- LY146032 administration significantly reduced intestinal colonization and prevented translocation when given before or during challenge.
- LY146032 did not effectively reduce bacterial populations or treat established extraintestinal infections once they occurred.
Conclusions:
- Streptomycin compromises gut barrier function, increasing S. faecalis colonization and translocation.
- LY146032 is effective in preventing S. faecalis translocation from the intestinal tract in a mouse model.
- LY146032 does not resolve established S. faecalis extraintestinal infections, highlighting the importance of early intervention.