title: High in vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug-resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea.
abstract: We evaluated the activity of the novel spiropyrimidinetrione AZD0914 (DNA gyrase inhibitor) against clinical gonococcal isolates and international reference strains (n=250), including strains with diverse multidrug resistance and extensive drug resistance. The AZD0914 MICs were substantially lower than those of most other currently or previously recommended antimicrobials. AZD0914 should be further evaluated, including in vitro selection, in vivo emergence and mechanisms of resistance, pharmacokinetics/pharmacodynamics in humans, optimal dosing, and performance, in appropriate randomized and controlled clinical trials.
authors: WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
authors: Susanne
authors: S
authors: Jacobsson
authors: WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
authors: Daniel
authors: D
authors: Golparian
authors: Infection iMed, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors: Richard A
authors: RA
authors: Alm
authors: Infection iMed, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors: Michael
authors: M
authors: Huband
authors: Infection iMed, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
authors: John
authors: J
authors: Mueller
authors: Statens Serum Institut, Copenhagen, Denmark.
authors: Jorgen Skov
authors: JS
authors: Jensen
authors: National Institute of Infectious Diseases, Tokyo, Japan.
authors: Makoto
authors: M
authors: Ohnishi
authors: WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden magnus.unemo@orebroll.se.
authors: Magnus
authors: M
authors: Unemo
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001463:Barbiturates / Q000494:pharmacology*; D027081:DNA Gyrase / Q000187:drug effects*; D024901:Drug Resistance, Multiple, Bacterial; D006069:Gonorrhea / Q000188:drug therapy*; D007555:Isoxazoles; D008826:Microbial Sensitivity Tests; D009025:Morpholines; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000302:isolation & purification; D023303:Oxazolidinones; D013141:Spiro Compounds / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001463:Barbiturates; D007555:Isoxazoles; D009025:Morpholines; D023303:Oxazolidinones; D013141:Spiro Compounds; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase; C000599190:zoliflodacin