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Treatment of experimental endocarditis caused by multidrug resistant Enterococcus faecium with ramoplanin and
D Landman1, J M Quale, S Burney
1Department of Medicine, Department of Veterans Affairs Medical Center, Brooklyn, New York, USA.
Abstract:
Antibiotic resistant strains of enterococci are being isolated with increasing frequency. Effective treatment of infections caused by Enterococcus faecium resistant to ampicillin, vancomycin and aminoglycosides has not been established. We studied the activity of ramoplanin, a new lipoglycopeptide antibiotic, against two strains of multidrug resistant E. faecium. In time kill studies, ramoplanin was bactericidal against both strains, but not in the presence of 50% serum. The combination of ramoplanin and penicillin was bactericidal even in the presence of serum. In rabbits with experimental endocarditis neither penicillin nor ramoplanin significantly reduced vegetation colony counts when given alone, although ramoplanin significantly reduced spleen and kidney bacterial counts of both strains. The combination of ramoplanin plus penicillin resulted in a significant reduction of vegetation bacterial counts (-3.2 and -3.7 log10 cfu/g for strains VA3 and MMC3, respectively, P < 0.01). All spleen cultures and 9 out of 10 kidney cultures from each strain were sterile following combination therapy. While ramoplanin will not be available for parenteral therapy, further research into the development of other lipoglycopeptide antibiotics is warranted.
Insights
Ramoplanin, a novel lipoglycopeptide, shows promise against multidrug-resistant Enterococcus faecium infections. Combination therapy with penicillin significantly reduced bacterial counts in experimental endocarditis models.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Increasing incidence of antibiotic-resistant enterococci, particularly multidrug-resistant Enterococcus faecium.
- Lack of established effective treatments for infections caused by ampicillin, vancomycin, and aminoglycoside-resistant E. faecium.
Purpose of the Study:
- To evaluate the activity of ramoplanin, a new lipoglycopeptide antibiotic, against multidrug-resistant Enterococcus faecium.
- To assess the efficacy of ramoplanin, alone and in combination with penicillin, in a rabbit model of experimental endocarditis.
Main Methods:
- In vitro time-kill studies to determine bactericidal activity of ramoplanin.
- In vivo experimental endocarditis model in rabbits to evaluate treatment efficacy.
- Assessment of vegetation, spleen, and kidney bacterial colony counts.
Main Results:
- Ramoplanin demonstrated bactericidal activity in vitro, but this was negated by 50% serum.
- The combination of ramoplanin and penicillin was bactericidal in the presence of serum.
- In vivo, ramoplanin alone reduced bacterial counts in spleen and kidneys but not vegetations.
- Combination therapy with ramoplanin and penicillin significantly reduced vegetation bacterial counts and sterilized spleen and kidney cultures.
Conclusions:
- Ramoplanin shows potential for treating multidrug-resistant Enterococcus faecium infections, particularly in combination with penicillin.
- Further research into lipoglycopeptide antibiotics for parenteral therapy is warranted.
- Combination therapy offers a promising strategy against challenging enterococcal infections.