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Triple combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a highly penicillin-and
F Caron1, J F Lemeland, G Humbert
1Groupe de Recherche en Infections Expérimentales, Hôpital Charles Nicolle, Rouen, France.
Abstract:
A combination of low-dose penicillin (75,000 IU/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IU/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to beta-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 micrograms/mL) and vancomycin (MIC, 512 micrograms/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killing-curve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination.
Insights
A novel high-dose penicillin-vancomycin-gentamicin combination effectively treated rabbit endocarditis caused by highly resistant Enterococcus faecium. This approach shows promise, but resistance emergence needs monitoring.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Endocarditis is a serious infection often caused by Enterococcus faecium.
- Treatment of resistant strains, particularly those with high-level resistance to penicillin and vancomycin, presents significant challenges.
- Optimizing antibiotic regimens is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the efficacy of different antibiotic combinations against Enterococcus faecium strains with high-level resistance to penicillin and vancomycin.
- To assess the in vitro and in vivo effectiveness of high-dose penicillin-vancomycin-gentamicin therapy.
- To investigate the potential for resistance development to synergistic antibiotic combinations.
Main Methods:
- In vitro killing-curve studies were performed to assess bactericidal and bacteriostatic activity.
- Rabbit endocarditis models were used to evaluate the in vivo efficacy of various antibiotic regimens.
- Minimum Inhibitory Concentrations (MICs) were determined for Enterococcus faecium strains against tested antibiotics.
Main Results:
- High-dose penicillin-gentamicin and vancomycin-gentamicin regimens were ineffective in vitro and in vivo against highly resistant E. faecium.
- High-dose penicillin-vancomycin demonstrated bacteriostatic effects in vitro and limited efficacy in vivo.
- High-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits, despite potential for resistance emergence.
Conclusions:
- High-dose penicillin-vancomycin-gentamicin is a promising therapeutic option for endocarditis caused by highly resistant Enterococcus faecium.
- The emergence of bacterial subpopulations resistant to this synergistic combination warrants further investigation and clinical monitoring.
- Further research is needed to fully understand the clinical utility and long-term implications of this combination therapy.