Antimicrobial Agents and Chemotherapy, March 1999, p. 476-482, Vol. 43, No. 3
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Institut National de la Santé et de la
Recherche Médicale,
Received 11 September 1998/Returned for modification 23 October
1998/Accepted 30 December 1998
The activity of vancomycin and teicoplanin combined with gentamicin
was investigated in vitro against strains of Enterococcus faecalis resistant to vancomycin and susceptible to teicoplanin (VanB type) and against mutants that had acquired resistance to teicoplanin by three different mechanisms. In vitro, gentamicin selected mutants with two- to sixfold increases in the level of resistance to this antibiotic at frequencies of 10
6 to
10
7. Teicoplanin selected teicoplanin-resistant mutants
at similar frequencies. Both mutations were required to abolish the
activity of the gentamicin-teicoplanin combination. As expected,
simultaneous acquisition of the two types of mutations was not
observed. In therapy with gentamicin or teicoplanin alone, each
selected mutants in three of seven rabbits with aortic endocarditis due
to VanB-type E. faecalis BM4275. The vancomycin-gentamicin
combination selected mutants that were resistant to gentamicin and to
the combination. In contrast, the teicoplanin-gentamicin regimen
prevented the emergence of mutants resistant to one or both components
of the combination. These results suggest that two mutations are also required to suppress the in vivo activity of the teicoplanin-gentamicin combination.
*
Corresponding author. Present address: Unité de
Médecine Interne, Hôpital Beaujon, 100 boulevard du
Général Leclerc, 92118 Clichy Cedex, France. Phone: (33)
(1) 40 87 58 90. Fax: (33) (1) 40 87 54 95. E-mail:
bruno.fantin{at}bjn.ap-hop-paris.fr.
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