ArticleAntimicrobial agents and chemotherapy2006
The anti-methicillin-resistant Staphylococcus aureus quinolone WCK 771 has potent activity against sequentially selected mutants, has a narrow mutant selection window against quinolone-resistant Staphylococcus aureus, and preferentially targets DNA gyrase.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 34 citations in OpenAlex.
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- Meeting the Unmet Need in the Management of MDR Gram-Positive Infections with Oral Bactericidal Agent Levonadifloxacin.Critical care research and practice · 2022Review
- Uptake of Ozenoxacin and Other Quinolones in Gram-Positive Bacteria.International journal of molecular sciences · 2021Article
- In Vitro activity of a Novel Benzoquinolizine Antibiotic, Levonadifloxacin (WCK 771) against Blood Stream Gram-Positive Isolates from a Tertiary Care Hospital.Journal of laboratory physicians · 2020Article
- Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms.Microorganisms · 2020Review
- The Persister Character of Clinical Isolates ofFrontiers in microbiology · 2020Article
- Article
- Overview of methicillin resistantOrthopedic reviews · 2019Article
- Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence.Drug design, development and therapy · 2019Review
- Investigational drugs to treat methicillin-resistant Staphylococcus aureus.Expert opinion on investigational drugs · 2016Review
- Pipeline of Known Chemical Classes of Antibiotics.Antibiotics (Basel, Switzerland) · 2013Review
- Antistaphylococcal activities of the new fluoroquinolone JNJ-Q2.Antimicrobial agents and chemotherapy · 2011Article
- In vitro antibacterial activities of JNJ-Q2, a new broad-spectrum fluoroquinolone.Antimicrobial agents and chemotherapy · 2010Article
- In vitro activity of the quinolone WCK 771 against recent U.S. hospital and community-acquired Staphylococcus aureus pathogens with various resistance types.Antimicrobial agents and chemotherapy · 2009Article
- Prescription-Event Monitoring Study on Safety and Efficacy of Levonadifloxacin (Oral and I.V.) in Management of Bacterial Infections: Findings of Real-World Observational Study.International journal of applied & basic medical researchArticle
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
WCK 771 is a broad-spectrum fluoroquinolone with enhanced activity against quinolone-resistant staphylococci. To understand the impact of the target-level interactions of WCK 771 on its antistaphylococcal pharmacodynamic properties, we determined the MICs for genetically defined mutants and studied the mutant prevention concentrations (MPCs), the frequency of mutation, and the cidality against the wild type and double mutants. There was a twofold increase in the MICs of WCK 771 for single gyrA mutants, indicating that DNA gyrase is its primary target. All first- and second-step mutants selected by WCK 771 revealed gyrA and grlA mutations, respectively. The MICs of WCK 771 and clinafloxacin were found to be superior to those of other quinolones against strains with double and triple mutations. WCK 771 was also cidal for high-density double mutants at low concentrations. WCK 771 and clinafloxacin showed narrow mutant selection windows compared to those of the other quinolones. Against a panel of 50 high-level quinolone-resistant clinical isolates of staphylococci (ciprofloxacin MIC > or = 16 microg/ml), the WCK 771 MPCs were < or =2 microg/ml for 68% of the strains and < or =4 microg/ml for 28% of the strains. Our results demonstrate that gyrA is the primary target of WCK 771 and that it has pharmacodynamic properties remarkably different from those of quinolones with dual targets (garenoxacin and moxifloxacin) and topoisomerase IV-specific quinolones (trovafloxacin). WCK 771 displayed an activity profile comparable to that of clinafloxacin, a dual-acting quinolone with a high affinity to DNA gyrase. Overall, the findings signify the key role of DNA gyrase in determining the optimal antistaphylococcal features of quinolones.
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