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

Susanne Jacobsson; Daniel Golparian; Richard A Alm; Michael Huband; John Mueller; Jorgen Skov Jensen; Makoto Ohnishi; Magnus Unemo

doi:10.1128/AAC.03090-14

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

Antimicrob Agents Chemother. 2014 Sep;58(9):5585-8. doi: 10.1128/AAC.03090-14. Epub 2014 Jun 30.

Authors

Susanne Jacobsson¹, Daniel Golparian¹, Richard A Alm², Michael Huband², John Mueller², Jorgen Skov Jensen³, Makoto Ohnishi⁴, Magnus Unemo⁵

Affiliations

¹ 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.
² Infection iMed, AstraZeneca R&D Boston, Waltham, Massachusetts, USA.
³ Statens Serum Institut, Copenhagen, Denmark.
⁴ National Institute of Infectious Diseases, Tokyo, Japan.
⁵ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / therapeutic use
Barbiturates / pharmacology*
DNA Gyrase / drug effects*
Drug Resistance, Multiple, Bacterial
Gonorrhea / drug therapy*
Isoxazoles
Microbial Sensitivity Tests
Morpholines
Neisseria gonorrhoeae / drug effects*
Neisseria gonorrhoeae / isolation & purification
Oxazolidinones
Spiro Compounds / pharmacology*
Topoisomerase II Inhibitors / pharmacology*

Substances

Anti-Bacterial Agents
Barbiturates
Isoxazoles
Morpholines
Oxazolidinones
Spiro Compounds
Topoisomerase II Inhibitors
DNA Gyrase
zoliflodacin