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Absence of synergistic activity between ampicillin and vancomycin against highly vancomycin-resistant enterococci
E Cercenado1, G M Eliopoulos, C B Wennersten
1Department of Medicine, New England Deaconess Hospital, Boston, Massachusetts.
Abstract:
The emergence of clinical enterococcal isolates resistant to both ampicillin and vancomycin is a cause of great concern, as there are few therapeutic alternatives for treatment of infections caused by such organisms. We evaluated the effects of the combination of ampicillin with vancomycin against vancomycin-resistant clinical enterococcal isolates. Using both the checkerboard technique and time-kill curves, we examined 28 strains of enterococci (17 Enterococcus faecalis and 11 Enterococcus faecium strains) with different levels of resistance to vancomycin. Of these, 15 strains were also highly gentamicin resistant, and 9 demonstrated resistance to ampicillin. Only seven strains of E. faecalis were inhibited synergistically by the combination of vancomycin with ampicillin, and even then, the concentrations of vancomycin at which synergism was demonstrated were above levels achievable in serum. None of the ampicillin-resistant isolates (all E. faecium) were inhibited synergistically at any concentration of the drugs. In no instance was bactericidal synergism observed, and in most cases the combination resulted in less killing than with ampicillin alone. Antagonism was not observed at clinically relevant concentrations. The results of this study suggest that the combination of vancomycin with ampicillin has little to offer against these emerging pathogens.
Insights
The combination of ampicillin and vancomycin offers limited benefit against emerging vancomycin-resistant enterococci. This study found minimal synergistic effects, with ampicillin alone often proving more effective in killing these difficult-to-treat pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Emergence of ampicillin and vancomycin-resistant enterococci poses a significant clinical challenge.
- Limited therapeutic options exist for infections caused by these multidrug-resistant organisms.
Purpose of the Study:
- To evaluate the in vitro efficacy of combining ampicillin with vancomycin against vancomycin-resistant clinical enterococcal isolates.
- To determine if synergistic or additive effects occur with this drug combination.
Main Methods:
- Checkerboard technique and time-kill curves were employed.
- 28 clinical enterococcal strains (17 Enterococcus faecalis, 11 Enterococcus faecium) with varying vancomycin resistance levels were tested.
- Isolates included strains with high-level gentamicin resistance and ampicillin resistance.
Main Results:
- Synergistic inhibition by vancomycin-ampicillin combination was observed in only seven Enterococcus faecalis strains, at concentrations exceeding achievable serum levels.
- No synergistic inhibition was seen in any ampicillin-resistant Enterococcus faecium isolates.
- Bactericidal synergism was not observed; ampicillin alone was often more effective than the combination.
- Antagonism was not detected at clinically relevant concentrations.
Conclusions:
- The combination of vancomycin and ampicillin demonstrates limited clinical utility against vancomycin-resistant enterococci.
- This combination therapy is unlikely to be effective for treating infections caused by these emerging pathogens.