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In vitro evaluation of WIN 57273, a new broad-spectrum fluoroquinolone
Abstract:
WIN 57273 is a new fluoroquinolone that has an expanded spectrum of activity against Staphylococcus spp. (MIC for 90% of isolates [MIC90], 0.008 microgram/ml), Enterococcus faecalis (MIC90, 0.06 microgram/ml), Bacillus spp. (MIC90, 0.03 micrograms/ml), Listeria monocytogenes (MIC90, 0.06 microgram/ml), Streptococcus spp. (MIC90, 0.03 microgram/ml), and Bacteroides fragilis group strains (MIC90, 0.5 microgram/ml). Like other fluoroquinolone compounds, WIN 57273 was active against members of the family Enterobacteriaceae (97% of strains inhibited by less than or equal to 2 micrograms/ml), Haemophilus, Branhamella, and Neisseria strains (100% susceptible), Acinetobacter spp. (100% susceptible), and Pseudomonas aeruginosa (68% susceptible). We observed that WIN 57273 was very active against cephalosporin- or aminoglycoside-resistant gram-negative strains but shared cross-resistance with other fluoroquinolones. Increasing inoculum concentrations had minimal effects on WIN 57273 MICs, and the drug was considered to be bactericidal based on reference MBC and kill curve analyses. Unlike most previously studied drugs in this class, WIN 57273 had increased activity (three- to fourfold) at low pH. Rates of mutation to WIN 57273 resistance at eight times its MIC were in the range of 5.6 x 10(-8) to greater than 1.4 x 10(-9). This new compound possesses a wide potential spectrum of use, and it should be evaluated further by in vitro and in vivo studies.
Insights
WIN 57273, a novel fluoroquinolone antibiotic, demonstrates broad-spectrum activity against Gram-positive and Gram-negative bacteria, including resistant strains. It exhibits bactericidal properties and enhanced efficacy at low pH, warranting further investigation.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Fluoroquinolones are a class of synthetic broad-spectrum antibacterial drugs.
- Development of new antibiotics is crucial to combat rising antimicrobial resistance.
- Understanding the in vitro activity spectrum of novel agents is essential for guiding clinical application.
Purpose of the Study:
- To characterize the in vitro antibacterial spectrum of WIN 57273.
- To evaluate the activity of WIN 57273 against resistant bacterial strains.
- To assess the bactericidal activity and pH-dependent efficacy of WIN 57273.
Main Methods:
- Determination of Minimum Inhibitory Concentrations (MICs) against a panel of Gram-positive and Gram-negative bacteria.
- Evaluation of susceptibility testing at varying inoculum concentrations.
- Assessment of bactericidal activity using Minimum Bactericidal Concentration (MBC) and kill curve analyses.
- Investigation of activity at different pH levels.
Main Results:
- WIN 57273 exhibited potent activity against Staphylococcus spp., Enterococcus faecalis, Bacillus spp., Listeria monocytogenes, and Streptococcus spp.
- The compound was active against Enterobacteriaceae, Haemophilus, Branhamella, Neisseria, and Acinetobacter spp., with significant activity against cephalosporin/aminoglycoside-resistant Gram-negative strains.
- WIN 57273 demonstrated bactericidal activity, minimal impact of inoculum concentration on MICs, enhanced activity at low pH, and low mutation rates to resistance.
Conclusions:
- WIN 57273 possesses a broad spectrum of activity, including against resistant pathogens.
- Its bactericidal nature and favorable pH profile suggest potential clinical utility.
- Further in vitro and in vivo studies are warranted to fully evaluate WIN 57273.