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In vivo efficacy of the ketolide ABT-773 (cethromycin) against enterococci in a mouse peritonitis model
Suresh R Pai1, Kavindra V Singh, Barbara E Murray
1Center for the Study of Emerging and Re-Emerging Pathogens, The University of Texas Medical School, Houston, Texas 77030, USA.
Abstract:
Using six Enterococcus faecalis and five Enterococcus faecium strains, the ketolide ABT-773 (ABT), now known as cethromycin, was found to have in vivo efficacy against both erythromycin (ERY)-susceptible (Ery(s)) and -intermediate (Ery(i)) enterococci (ABT 50% protective doses [PD(50)s], 0.5 to 4.1 and 10.3 to 16.2 mg/kg of body weight, respectively). Against four highly Ery-resistant (Ery(r)) strains for which ABT MICs were low, ABT showed much greater activity (PD(50), 6.3 to 32.5 mg/kg) than ERY (PD(50), >200 mg/kg) but was not protective for strains for which ABT MICs were high. In conclusion, ABT-773 showed in vivo efficacy and considerably greater activity than ERY in a mouse peritonitis model.
Insights
The novel ketolide cethromycin (ABT-773) demonstrated significant in vivo efficacy against both erythromycin-susceptible and -intermediate enterococci strains in a mouse model. It also showed superior activity compared to erythromycin against certain resistant strains.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Enterococcus species are a significant cause of nosocomial infections.
- Antibiotic resistance, particularly to erythromycin, is a growing concern in treating enterococcal infections.
- Novel antimicrobial agents are needed to combat resistant bacterial strains.
Purpose of the Study:
- To evaluate the in vivo efficacy of the ketolide ABT-773 (cethromycin) against Enterococcus faecalis and Enterococcus faecium.
- To compare the efficacy of ABT-773 with erythromycin (ERY) in a mouse peritonitis model.
- To assess the activity of ABT-773 against erythromycin-resistant enterococcal strains.
Main Methods:
- A mouse peritonitis model was used to assess the efficacy of ABT-773.
- Six Enterococcus faecalis and five Enterococcus faecium strains were utilized.
- The 50% protective dose (PD(50)) was determined for ABT-773 and erythromycin.
Main Results:
- ABT-773 exhibited in vivo efficacy against erythromycin-susceptible and -intermediate enterococci.
- ABT-773 demonstrated significantly greater activity than erythromycin against highly erythromycin-resistant strains with low ABT minimum inhibitory concentrations (MICs).
- Efficacy of ABT-773 was strain-dependent, with reduced activity against strains having high ABT MICs.
Conclusions:
- ABT-773 (cethromycin) shows promising in vivo efficacy against enterococci.
- The ketolide ABT-773 offers a potential therapeutic advantage over erythromycin, especially for resistant strains.
- Further investigation into ABT-773's activity against diverse enterococcal isolates is warranted.
