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Triple-combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a moderately penicillin-
Abstract:
An in vitro bacteriostatic synergy between beta-lactam and glycopeptide antibiotics has been recently described against isolates of Enterococcus faecium moderately resistant to penicillin and highly resistant to vancomycin. The relevance of this synergy in a rabbit endocarditis model was evaluated. Penicillin was tested at low- (LoD) and high-dose (HiD) regimens, alone or combined with vancomycin and/or gentamicin. Compared with controls, after a 5-day treatment: LoD penicillin, vancomycin, gentamicin, LoD penicillin plus gentamicin or vancomycin, and vancomycin-gentamicin were not effective; LoD penicillin-vancomycin caused a small reduction of bacterial titers in vegetations that was strongly enhanced by adding gentamicin; HiD penicillin-gentamicin, the most effective regimen, was not significantly better than LoD penicillin-vancomycin-gentamicin. These results suggest that the relative in vivo inefficacy of penicillin-vancomycin might be related to the fact that this combination was poorly bactericidal, and the triple combination of LoD penicillin-vancomycin-gentamicin or the combination of HiD penicillin-gentamicin should be considered in the treatment of serious infections due to beta-lactam- and glycopeptide-resistant enterococci.
Insights
A novel antibiotic combination therapy shows promise for treating infections caused by drug-resistant Enterococcus faecium. Adding gentamicin to penicillin and vancomycin significantly improved outcomes in a rabbit model, suggesting a new treatment strategy.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- In vitro studies demonstrated bacteriostatic synergy between beta-lactam (penicillin) and glycopeptide (vancomycin) antibiotics against Enterococcus faecium strains with moderate penicillin resistance and high vancomycin resistance.
- The clinical relevance of this in vitro synergy for treating serious Enterococcus faecium infections remains to be fully elucidated.
Purpose of the Study:
- To evaluate the in vivo efficacy of penicillin-vancomycin combinations, with and without gentamicin, in a rabbit model of endocarditis caused by beta-lactam- and glycopeptide-resistant Enterococcus faecium.
Main Methods:
- Rabbits with endocarditis were treated for 5 days with various antibiotic regimens: low-dose (LoD) or high-dose (HiD) penicillin alone or combined with vancomycin and/or gentamicin.
- Bacterial titers in vegetations were quantified to assess treatment effectiveness compared to control groups.
Main Results:
- Monotherapy with LoD penicillin, vancomycin, or gentamicin, as well as combinations like LoD penicillin-gentamicin or vancomycin-gentamicin, showed no significant efficacy.
- The combination of LoD penicillin-vancomycin demonstrated a modest reduction in bacterial titers, which was substantially enhanced by the addition of gentamicin.
- The HiD penicillin-gentamicin regimen was highly effective but not significantly superior to the triple combination of LoD penicillin-vancomycin-gentamicin.
Conclusions:
- The in vivo inefficacy of the penicillin-vancomycin combination may stem from its limited bactericidal activity.
- A triple antibiotic combination including low-dose penicillin, vancomycin, and gentamicin, or a high-dose penicillin-gentamicin regimen, should be considered for treating severe infections caused by resistant enterococci.