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Selection of glycopeptide-resistant mutants of VanB-type Enterococcus faecalis BM4281 in vitro and in experimental
E Aslangul1, M Baptista, B Fantin
1Service de Médecine Interne, Institut National de la Santé et de la Recherche Médicale U13, Hôpital Bichat-Claude Bernard, Paris, France.
Abstract:
Enterococcus faecalis BM4281 is resistant to vancomycin, susceptible to teicoplanin (VanB phenotype), and intrinsically resistant to low levels of gentamicin. The efficacy of glycopeptides against BM4281 was investigated in a rabbit model of experimental endocarditis for reduction of bacterial counts in cardiac vegetations and selection of mutants with increased resistance to glycopeptides. Teicoplanin led to a 100-fold reduction of bacteria in the vegetations, whereas vancomycin had no effect. Monotherapy with either antibiotic selected mutants with homogeneous or heterogeneous resistance to high levels of both glycopeptides. Vancomycin also selected mutants that required the antibiotic for growth. The combination of gentamicin plus teicoplanin was bactericidal, prevented the emergence of mutants, and allowed sterilization of the vegetations in 25% of the rabbits, indicating that the combination may be an alternative if penicillin cannot be used against VanB-type enterococci.
Insights
Teicoplanin reduced Enterococcus faecalis BM4281 bacterial counts, while vancomycin did not. Combining gentamicin with teicoplanin was effective, preventing resistance and sterilizing infections in some cases.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Enterococcus faecalis BM4281 exhibits vancomycin resistance (VanB phenotype) and intrinsic gentamicin resistance.
- Investigating glycopeptide efficacy against VanB-type Enterococcus faecalis is crucial for treatment strategies.
Purpose of the Study:
- To evaluate the efficacy of vancomycin and teicoplanin, alone and in combination with gentamicin, against Enterococcus faecalis BM4281 in experimental endocarditis.
- To assess the selection of glycopeptide-resistant mutants under different treatment regimens.
Main Methods:
- A rabbit model of experimental endocarditis was used to study Enterococcus faecalis BM4281.
- Bacterial counts in cardiac vegetations were determined post-treatment.
- Mutant selection and resistance levels were analyzed.
Main Results:
- Teicoplanin significantly reduced bacterial load (100-fold), whereas vancomycin showed no effect.
- Monotherapy with either glycopeptide selected for high-level resistance to both agents.
- Vancomycin monotherapy also induced mutants requiring the drug for growth.
- The combination of gentamicin and teicoplanin was bactericidal, prevented mutant emergence, and achieved sterilization in 25% of rabbits.
Conclusions:
- Teicoplanin is more effective than vancomycin against VanB-type Enterococcus faecalis endocarditis in this model.
- Glycopeptide monotherapy can lead to the rapid emergence of high-level resistance.
- Gentamicin plus teicoplanin offers a promising alternative treatment for VanB-type enterococcal infections when penicillin is contraindicated.