Absence of synergistic activity between ampicillin and vancomycin against highly vancomycin-resistant enterococci

Author:

Cercenado E1,Eliopoulos G M1,Wennersten C B1,Moellering R C1

Affiliation:

1. Department 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference13 articles.

1. Cercenado E. G. M. Eliopoulos C. B. Wennersten and R. C. Moellering Jr. Influence of high-level gentamicin resistance and beta-hemolysis on susceptibility of enterococci to the bactericidal activities of ampicilin and vancomycin. Antimicrob. Agents Chemother. in press.

2. Clark N. F. Tenover B. Hill J. Swenson and R. Cooksey. 1991. Characterization of glycopeptide-resistant enterococci from 14 U.S. Hospitals abstr. 400. Program Abstr. 31st Intersci. Conf. Antimicrob. Agents Chemother. Chicago Ill.

3. Susceptibility of enterococci and Listenia nmnocytogenes to N-formimidoyl thienamycin alone and in combination with an aminoglycoside;Eliopoulos G. M.;Antimicrob. Agents Chemother.,1981

4. Increasing resistance to beta-lactam antibiotics among clinical isolates of Enterococcus faecium: a 22-year review at one institution;Grayson M. L.;Antimicrob. Agents Chemother.,1991

5. Concomitant high-level vancomycin and penicillin resistance in clinical isolates of enterococci;Handwerger S.;Clin. Infect. Dis.,1992

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