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Activity of LY146032 in vitro and in experimental enterococcal pyelonephritis
Abstract:
The efficacy of LY146032 (LY), a new lipopeptide antibiotic, was compared with that of vancomycin, ciprofloxacin, ceftriaxone, imipenem, and gentamicin and combinations of LY-ceftriaxone, LY-imipenem, and LY-gentamicin against 15 strains of Streptococcus (Enterococcus) faecalis by microtiter dilution and checkerboard techniques. LY was effective within a very narrow range of drug concentrations (from 0.125 to 2.0 micrograms/ml) and was more active than other agents tested against S. faecalis. Enhanced inhibition of S. faecalis was seen more frequently with combinations of either penicillin or ampicillin and an aminoglycoside than with combinations of LY and gentamicin, imipenem, or ceftriaxone. The in vivo efficacy of LY was compared with that of vancomycin and ampicillin alone and combinations of vancomycin-gentamicin, ampicillin-gentamicin, and LY-gentamicin in a rat model of chronic enterococcal pyelonephritis. At a dose of 10 mg/kg given twice daily, LY reduced the number of organisms per kidney significantly compared with that in infected untreated controls within 48 h after the initiation of therapy. At 20 mg/kg given once a day, LY was less effective but reduced colony counts significantly after 4 days of therapy, and its activity was comparable to that of vancomycin or vancomycin-gentamicin given twice daily. LY may be a promising agent for the treatment of enterococcal infections.
Insights
LY146032 (LY), a novel lipopeptide antibiotic, demonstrates potent activity against Enterococcus faecalis in vitro and in vivo. This promising new antibiotic warrants further investigation for treating enterococcal infections.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Enterococcus faecalis is a significant cause of nosocomial infections.
- Novel antibiotics are needed to combat rising antimicrobial resistance.
Purpose of the Study:
- To evaluate the in vitro and in vivo efficacy of LY146032 (LY) against Enterococcus faecalis.
- To compare LY with existing antibiotics and their combinations.
Main Methods:
- Microtiter dilution and checkerboard techniques were used for in vitro susceptibility testing.
- A rat model of chronic enterococcal pyelonephritis was employed for in vivo efficacy assessment.
Main Results:
- LY exhibited potent activity against S. faecalis in vitro, with a narrow effective concentration range.
- In vivo, LY significantly reduced bacterial kidney counts in a rat model, showing comparable efficacy to vancomycin at specific dosages.
Conclusions:
- LY146032 is a promising lipopeptide antibiotic with significant potential for treating enterococcal infections.
- Further research is recommended to explore LY's therapeutic applications.