ArticleAntimicrobial agents and chemotherapy2015
Characterization of the novel DNA gyrase inhibitor AZD0914: low resistance potential and lack of cross-resistance in Neisseria gonorrhoeae.
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 54 papers.
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Who cites it
54 citing papers in PubMed, 94 citations in OpenAlex.
- Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial.Lancet (London, England) · 2026Trial
- Single-Dose Pharmacokinetics, Excretion, and Metabolism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic, in Healthy Volunteers.Antimicrobial agents and chemotherapy · 2019Trial
- Genetic Background Modulates Zoliflodacin and Gepotidacin Cross-Resistance and Fitness in Neisseria gonorrhoeae.The Journal of infectious diseases · 2026Article
- Article
- Zoliflodacin: First Approval.Drugs · 2026Review
- Fluoroquinolone resistance-conferringbioRxiv : the preprint server for biology · 2026Article
- Treatment of Syphilis in Pregnancy and Congenital Syphilis: Current Evidence, Challenges, and Future Directions.Antibiotics (Basel, Switzerland) · 2026Review
- In Vitro Activity of Zoliflodacin AgainstAntibiotics (Basel, Switzerland) · 2026Article
- Gyrase and Topoisomerase IV as Antibacterial Targets for Gepotidacin and Zoliflodacin: Teaching Old Enzymes New Tricks.International journal of molecular sciences · 2026Review
- Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting againstACS infectious diseases · 2025Article
- CommensalAnnual review of microbiology · 2025Review
- Susceptibility ofPathogens (Basel, Switzerland) · 2025Article
- High susceptibility to the novel antimicrobial zoliflodacin amongIJID regions · 2025Article
- Interactions between Zoliflodacin andACS infectious diseases · 2024Article
- Efficacy of Zoliflodacin, a Spiropyrimidinetrione Antibiotic, Against Gram-Negative Pathogens.Current microbiology · 2024Article
- Congenital Syphilis: A Re-Emerging but Preventable Infection.Pathogens (Basel, Switzerland) · 2024Review
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Gonococcal resistance to zoliflodacin could emerge via transformation from commensal Neisseria species. An in-vitro transformation study.Scientific reports · 2024Article
- Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study.The Lancet. Microbe · 2023Article
- Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea,The Lancet regional health. Europe · 2023Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unmet medical need for novel intervention strategies to treat Neisseria gonorrhoeae infections is significant and increasing, as rapidly emerging resistance in this pathogen is threatening to eliminate the currently available treatment options. AZD0914 is a novel bacterial gyrase inhibitor that possesses potent in vitro activities against isolates with high-level resistance to ciprofloxacin and extended-spectrum cephalosporins, and it is currently in clinical development for the treatment of N. gonorrhoeae infections. The propensity to develop resistance against AZD0914 was examined in N. gonorrhoeae and found to be extremely low, a finding supported by similar studies with Staphylococcus aureus. The genetic characterization of both first-step and second-step mutants that exhibited decreased susceptibilities to AZD0914 identified substitutions in the conserved GyrB TOPRIM domain, confirming DNA gyrase as the primary target of AZD0914 and providing differentiation from fluoroquinolones. The analysis of available bacterial gyrase and topoisomerase IV structures, including those bound to fluoroquinolone and nonfluoroquinolone inhibitors, has allowed the rationalization of the lack of cross-resistance that AZD0914 shares with fluoroquinolones. Microbiological susceptibility data also indicate that the topoisomerase inhibition mechanisms are subtly different between N. gonorrhoeae and other bacterial species. Taken together, these data support the progression of AZD0914 as a novel treatment option for the oral treatment of N. gonorrhoeae infections.
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