Swiss white mice were given ampicillin, clindamycin, kanamycin, metronidazole, or streptomycin in drinking water for a period of 3 weeks. One week after the initiation of antibiotic administration, the treated mice and untreated control mice were challenged orally with approximately 108 viable, streptomycin-resistant (SR) Pseudomonas aeruginosa isolates. All five of the antibiotics decreased the resistance of the mice to intestinal colonization with SR P. aeruginosa, as reflected by an increased fecal carriage of the organism and an increase in population levels of SR P. aeruginosa in feces as compared with untreated controls. Metronidazole was least effective in this regard. The antibiotics lowered the dose of SR P. aeruginosa that resulted in implantation in 50% of the mice ID50 to various degrees. Administration of streptomycin, the most effective antibiotic, caused a 10,000-fold decrease in ID50 as compared with untreated controls. Oral inoculation of approximately 108 organisms of SR P. aeruginosa resulted in translocation of the organism to the * Corresponding author.

Streptomycin sulfate (5 mg/ml) was added to the drinking water of Swiss white mice. After treatment for 1 week, the mice were challenged orogastrically with 10(8) Pseudomonas aeruginosa cells. The organism failed to multiply in the intestinal tract of either treated or untreated animals, but could be recovered from contents and tissues after 48 h. In a previous study, Salmonella typhimurium was shown to multiply in the intestines of streptomycin-treated but not untreated mice when 10(3) organisms were used as inoculum. Streptomycin administration had little effect on Eh, protein or carbohydrate concentrations of cecal contents, or intestinal motility. However, it caused a statistically significant increase in water content and pH of contents and a decrease in the concentrations of acetic, propionic, butyric, and valeric acids. S. typhimurium multiplied in pooled cecal contents obtained from both streptomycin-treated and untreated animals, but its multiplication rate and total populations were significantly greater in contents from treated animals. P. aeruginosa did not multiply in contents from either treated or untreated mice. Similar results were obtained when the organisms were inoculated into nutrient broth adjusted to simulate the pH levels and volatile fatty acid (VFA) concentrations in cecal contents of treated and untreated mice. The addition of brain heart infusion broth to cecal contents from untreated animals, in concentrations that support multiplication of S. typhimurium and P. aeruginosa, did not reverse inhibition. The addition of VFA to cecal contents from treated animals to equal the concentration in cecal contents from untreated animals caused inhibition of a magnitude observed in cecal contents from untreated animals. The results indicate that VFA operating at the pH level of cecal contents of conventional mice inhibit the multiplication of both S. typhimurium and P. aeruginosa and restrict colonization of the intestine by these organisms. The decrease in VFA concentrations that occurs as a result of streptomycin administration adequately explains the increased susceptibility of treated mice to colonization with S. typhimurium. It does not explain the increased susceptibility of treated mice to P. aeruginosa colonization, however.

No 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 , abstr. no. 1029, 1985) reported that nosocomial enterococcal infections had increased from 3.4 to 3.8 per 1,000 hospital discharges between 1980 and 1984; during this same period, the incidence of enterococcal bacteremias almost doubled (0.12 to 0.20 per 1,000 hospital discharges). Overall infection rates were highest on surgery services (5.6 per 1,000 discharges), with the urinary tract, surgical wounds, and blood accounting for 59, 23, and 4% of the infections, respectively. This may represent a shift in the traditional epidemiology of enterococcal infections, which have typically involved the biliary tract, genitourinary tract, or heart valves. Perhaps even more ominous is the fact that isolates recovered from surgical infections are increasingly resistant to aminoglycosides (20).Surgical infections involving enterococci, especially Streptococcus (Enterococcus)faecalis, often occurin seriously ill patients with peritonitis who have received broad-spectrum antibiotic therapy effective against most enteric pathogens except enterococci (5). We have observed that in some of these patients, enterococcal bacteremia may arise even when the organism has not been previously recovered from any known septic focus, including the urinary tract, and in the apparent absence of endocarditis, biliary tract disease, or pus (S. Dougherty, unpublished data). Global depression of host immune defenses usually appears to be present as well. * Corresponding author.We speculate that in seriously ill patients with peritonitis who receive broad-spectrum antibiotic therapy ineffective against enterococci, intestinal overgrowth of these organisms and extraintestinal spread by translocation sometimes occurs.Surprisingly little experimental data exist, however, on the ability of enterococci to translocate to extraintestinal sites (18) or on the ability of specific antibiotic therapy to prevent translocation. In this report, we describe S. faecalis colonization of the intestines of mice and translocation of the organism to extraintestinal sites. We further report on the effectiveness of the experimental antibiotic LY146032 (Eli Lilly & Co., Indianapolis, Ind.) in preventing these extraintestinal infections and in ameliorating infections already established. MATERIALS AND METHODSBacterial strain. The S. faecalis strain was kindly provided by Robert C. Moellering, New England Deaconess Hospital and Harvard Medical School. The MIC of streptomycin sulfate for this strain was greater than 10,000 ,ug/ml.Mice. Outbred Swiss White mice (Cox variety; Laboratory Supply Co., Indianapolis, Ind.) were used in all experiments. The mice were housed individually in cages with wire-mesh bottoms...