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Effective treatment of multidrug-resistant enterococcal experimental endocarditis with combinations of cell
C M Brandt1, M S Rouse, N W Laue
1Infectious Diseases Research Laboratory, Mayo Clinic, Rochester, Minnesota, USA.
Abstract:
The efficacy of treatment with a combination of ampicillin, imipenem, and vancomycin was compared with that of two-drug combinations or monotherapy in a model of experimental endocarditis using a strain of Enterococcus faecium with high-level resistance to vancomycin and moderate intrinsic resistance to ampicillin and imipenem. In vitro time-kill synergy studies demonstrated bactericidal synergistic activity only for the triple combination. In vivo, monotherapy with vancomycin was not effective. Treatment with either ampicillin or imipenem alone or in combination with vancomycin resulted in <4 log10 reduction in colony-forming units (cfu) per gram of vegetation. The combination of ampicillin with imipenem was highly active (an additional 5 log10 reduction in cfu per gram of vegetation compared with the most active single agent), but efficacy was not increased by the addition of vancomycin to ampicillin and imipenem. Therapy with the combination of ampicillin and imipenem may be effective for some strains of multidrug-resistant enterococcal infections.
Insights
A combination of ampicillin and imipenem showed effectiveness against multidrug-resistant enterococci infections. Adding vancomycin did not improve outcomes in experimental endocarditis models.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Multidrug-resistant enterococci pose a significant threat in healthcare settings.
- High-level vancomycin resistance in Enterococcus faecium complicates treatment options.
- Experimental endocarditis models are crucial for evaluating antibiotic efficacy.
Purpose of the Study:
- To compare the efficacy of ampicillin, imipenem, and vancomycin combinations against resistant Enterococcus faecium.
- To evaluate the synergistic activity of antibiotic combinations in vitro and in vivo.
- To determine the potential of ampicillin-imipenem combination therapy for resistant enterococcal infections.
Main Methods:
- In vitro time-kill synergy studies were performed.
- An experimental endocarditis model was utilized.
- Bacterial load was quantified as colony-forming units (cfu) per gram of vegetation.
Main Results:
- Only the triple combination (ampicillin, imipenem, vancomycin) demonstrated synergistic bactericidal activity in vitro.
- Vancomycin monotherapy was ineffective in vivo.
- Ampicillin and imipenem combination therapy showed significant reduction in bacterial load, with vancomycin addition not improving efficacy.
Conclusions:
- The combination of ampicillin and imipenem demonstrates significant activity against multidrug-resistant Enterococcus faecium in experimental endocarditis.
- Vancomycin does not enhance the efficacy of ampicillin-imipenem combination therapy in this model.
- Ampicillin-imipenem combination therapy may represent a viable treatment option for specific multidrug-resistant enterococcal infections.