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WIN 57273, a new fluoroquinolone with enhanced in vitro activity versus gram-positive pathogens
1Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
Abstract:
WIN 57273 is a new fluoroquinolone with excellent in vitro activity versus gram-positive pathogens, including methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis and gentamicin-susceptible and -resistant Enterococcus faecalis. We compared the microdilution MICs and MBCs of this compound to those of other antimicrobial agents for more than 30 clinical isolates of each of these groups of organisms and found that with few exceptions, it was at least 10 times more active than all other drugs tested. Selection for resistance to ciprofloxacin (greater than or equal to 5 micrograms/ml) or WIN 57273 (greater than or equal to 0.16 microgram/ml) by the gradient plate method produced mutants with diminished susceptibility to the other fluoroquinolone; however, the MICs and MBCs of WIN 57273 for such strains were still quite low and remained below the preliminary susceptibility breakpoint (less than or equal to 2 micrograms/ml). Spontaneous mutations conferring resistance to two and five times the WIN 57273 MIC were detectable at low frequencies for S. aureus and S. epidermidis; such mutations were virtually undetectable for E. faecalis. Further testing is necessary to establish if the effectiveness of WIN 57273 is maintained in vivo, first in animals and then in humans with infections caused by methicillin-susceptible and -resistant strains of S. aureus and S. epidermidis or gentamicin-susceptible and -resistant strains of E. faecalis.
Insights
WIN 57273, a novel fluoroquinolone, demonstrates potent in vitro activity against Gram-positive bacteria like Staphylococcus aureus and Enterococcus faecalis. It shows significantly higher potency than other tested agents, with low resistance development potential.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Gram-positive bacterial infections pose significant therapeutic challenges.
- Emerging resistance to existing antibiotics necessitates the development of new agents.
- Fluoroquinolones are a critical class of antibiotics with broad-spectrum activity.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of WIN 57273 against key Gram-positive pathogens.
- To compare the efficacy of WIN 57273 with existing antimicrobial agents.
- To assess the potential for resistance development to WIN 57273.
Main Methods:
- Microdilution Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays were performed.
- Over 30 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis were tested.
- Resistance selection was induced using the gradient plate method.
Main Results:
- WIN 57273 exhibited potent in vitro activity against methicillin-susceptible and -resistant S. aureus and S. epidermidis, and gentamicin-susceptible and -resistant E. faecalis.
- WIN 57273 was at least 10 times more active than other tested antimicrobial agents.
- Mutants selected for resistance to ciprofloxacin or WIN 57273 showed diminished susceptibility to the other fluoroquinolone, but WIN 57273 MICs remained low.
- Spontaneous resistance mutations were detected at low frequencies in S. aureus and S. epidermidis, and were virtually undetectable in E. faecalis.
Conclusions:
- WIN 57273 demonstrates excellent in vitro activity against clinically relevant Gram-positive bacteria.
- The compound shows a low frequency of spontaneous resistance development.
- Further in vivo studies are warranted to confirm the clinical efficacy of WIN 57273.