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Persistence of vancomycin-resistant Enterococcus faecium gastrointestinal tract colonization in antibiotic-treated
1Infectious Disease Section, Department of Veterans Affairs Medical Center, East Orange, New Jersey 07018, USA.
Abstract:
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 log10 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.
Insights
Antibiotic treatment can lead to vancomycin-resistant Enterococcus faecium (VREF) colonization in the gastrointestinal tract. A novel streptogramin antibiotic, RP 59500, effectively reduced VREF levels but did not achieve sustained eradication in mice.
Area of Science:
- Microbiology
- Pharmacology
- Gastroenterology
Background:
- Vancomycin-resistant Enterococcus faecium (VREF) colonization is linked to prior antibiotic use.
- The gastrointestinal tract is a primary reservoir for VREF.
- Understanding VREF colonization dynamics is crucial for infection control.
Purpose of the Study:
- To investigate the establishment and persistence of VREF colonization in a mouse model.
- To evaluate the efficacy of the streptogramin antibiotic RP 59500 in eradicating VREF.
- To explore potential alternative strategies for VREF colonization control.
Main Methods:
- Swiss Webster mice were pretreated with streptomycin and cefotetan to induce VREF colonization.
- A characterized VREF strain (E. faecium 228) was administered orally.
- RP 59500 was administered orally to colonized mice; vancomycin-sensitive E. faecium and Lactobacillus spp. were also tested for eradication potential.
Main Results:
- Persistent high-concentration VREF colonization (>8.0 log10 CFU/g) was established in antibiotic-treated mice.
- RP 59500 treatment led to undetectable VREF in feces (<3.0 CFU/g) after 14 days, but VREF returned post-treatment.
- Attempts to eradicate VREF with vancomycin-sensitive E. faecium or Lactobacillus spp. were unsuccessful during ongoing antibiotic treatment.
Conclusions:
- Antibiotic-induced VREF colonization can be established and maintained in the mouse GI tract.
- RP 59500 demonstrates potent but non-curative activity against VREF colonization.
- The hepatobiliary system may serve as an additional reservoir for VREF.