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Efficacy of telithromycin (HMR 3647) against enterococci in a mouse peritonitis model
K V Singh1, K K Zscheck, B E Murray
1Center for the Study of Emerging and Re-Emerging Pathogens, The University of Texas Medical School, Houston, Texas 77030, USA. Kavindra.Singh@uth.tmc.edu
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).
Insights
Telithromycin (TEL) demonstrated superior in vivo efficacy against enterococci compared to erythromycin (ERY). However, TEL
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Enterococcus species are significant human pathogens.
- Antibiotic resistance in Enterococcus strains is a growing concern.
- Macrolide antibiotics like erythromycin (ERY) are used to treat enterococcal infections.
Purpose of the Study:
- To evaluate the in vivo efficacy of telithromycin (TEL) and ERY against Enterococcus faecalis and Enterococcus faecium.
- To assess the impact of erythromycin resistance on TEL's efficacy.
- To compare TEL's in vivo activity with ERY and quinupristin-dalfopristin.
Main Methods:
- A mouse peritonitis model was utilized.
- Four strains of Enterococcus faecalis and three strains of Enterococcus faecium were tested.
- Bacterial isolates exhibited varying susceptibilities to TEL and ERY.
Main Results:
- TEL showed high in vivo activity against Ery-susceptible (Ery(s)) and Ery-intermediate (Ery(i)) strains.
- TEL exhibited reduced efficacy against Ery-resistant (Ery(r)) strains, though a second dose partially restored activity.
- Quinupristin-dalfopristin also showed reduced efficacy against Ery(r) E. faecium strains.
Conclusions:
- TEL is more potent in vivo against enterococci than ERY.
- The presence of erm(B)-mediated Ery(r) lowers TEL's activity.
- Understanding resistance mechanisms is crucial for effective antibiotic therapy.