Efficacy of telithromycin (HMR 3647) against enterococci in a mouse peritonitis model

Abstract

We used a mouse peritonitis model to evaluate the in vivo efficacy of telithromycin (HMR 3647) (TEL) and erythromycin (ERY) against four strains of Enterococcus faecalis and three strains of Enterococcus faecium with differing susceptibilities to TEL. TEL was highly active in vivo against Ery-susceptible (Ery(s)) and -intermediate (Ery(i)) strains (MIC of TEL = 0.015 to 0.062 microg/ml) and showed less efficacy against Ery-resistant (Ery(r)) isolates (MIC of TEL = 4 to 16 microg/ml), although this was overcome in part by a second subcutaneous dose. Quinupristin-dalfopristin was also noted to have less efficacy against Ery(r) versus Ery(s) or Ery(i) E. faecium strains, but this difference was reduced by intravenous administration. In conclusion, TEL was more potent in vivo against enterococci than was ERY; its activity was lowered by the presence of erm(B)-mediated Ery(r).

FIG. 1

(A) Survival and dose-response curve following therapy with TEL or ERY of peritonitis caused by E. faecalis strain TX0921 (HH22 Bla⁺ Gen^r) given by the s.c. route (single dose). (B) Survival and dose-response curve following therapy with TEL or ERY of peritonitis caused by E. faecium strain TX0016.01-Ery^c given by the s.c. route (single dose).