ArticleAntimicrobial agents and chemotherapy2015
In vitro antibacterial activity of AZD0914, a new spiropyrimidinetrione DNA gyrase/topoisomerase inhibitor with potent activity against Gram-positive, fastidious Gram-Negative, and atypical bacteria.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- Thorough QT Study To Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults.Antimicrobial agents and chemotherapy · 2021Trial
- Single-Dose Pharmacokinetics, Excretion, and Metabolism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic, in Healthy Volunteers.Antimicrobial agents and chemotherapy · 2019Trial
- Zoliflodacin for Urogenital Gonorrhea Infections.The Annals of pharmacotherapy · 2026Review
- Zoliflodacin: First Approval.Drugs · 2026Review
- Article
- Gyrase and Topoisomerase IV as Antibacterial Targets for Gepotidacin and Zoliflodacin: Teaching Old Enzymes New Tricks.International journal of molecular sciences · 2026Review
- The postantibiotic effect-like effect of photothermal agents: evidence from IR780 nanoparticles and indocyanine green.Frontiers in pharmacology · 2026Article
- Interactions between Zoliflodacin andACS infectious diseases · 2024Article
- Efficacy of Zoliflodacin, a Spiropyrimidinetrione Antibiotic, Against Gram-Negative Pathogens.Current microbiology · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Evaluating the efficacy of different antibiotics against Neisseria gonorrhoeae: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.BMC infectious diseases · 2024Article
- In Silico and In Vitro Identification of 1,8-Dihydroxy-4,5-dinitroanthraquinone as a New Antibacterial Agent againstMolecules (Basel, Switzerland) · 2023Article
- Emerging threat of antimicrobial resistance in Neisseria gonorrhoeae: pathogenesis, treatment challenges, and potential for vaccine development.Archives of microbiology · 2023Review
- Stimulating Transcription in Antibiotic-Tolerant Escherichia coli Sensitizes It to Fluoroquinolone and Nonfluoroquinolone Topoisomerase Inhibitors.Antimicrobial agents and chemotherapy · 2023Article
- Spiropyrimidinetriones: a Class of DNA Gyrase Inhibitors with Activity against Mycobacterium tuberculosis and without Cross-Resistance to Fluoroquinolones.Antimicrobial agents and chemotherapy · 2022Article
- Application of Principal Component Analysis (PCA) to the Evaluation and Screening of Multiactivity Fungi.Journal of Ocean University of China : JOUC · 2022Article
- Using a public database of Neisseria gonorrhoeae genomes to detect mutations associated with zoliflodacin resistance.The Journal of antimicrobial chemotherapy · 2021Article
- Bayesian Modeling and Intrabacterial Drug Metabolism Applied to Drug-ResistantACS infectious diseases · 2021Article
- Review
- Susceptibility Trends of Zoliflodacin against Multidrug-ResistantAntimicrobial agents and chemotherapy · 2021Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potent in vitro antibacterial activity against key Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzae and Neisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance in S. aureus, and if mutants were obtained, the mutations mapped to gyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration and in vitro time-kill studies. In in vitro checkerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potent in vitro antibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.