In Vitro Activity of AZD0914, a Novel Bacterial DNA Gyrase/Topoisomerase IV Inhibitor, against Clinically Relevant Gram-Positive and Fastidious Gram-Negative Pathogens.

Abstract

AZD0914, a new spiropyrimidinetrione bacterial DNA gyrase inhibitor with a novel mode of inhibition, has activity against bacterial species commonly cultured from patient infection specimens, including fluoroquinolone-resistant isolates. This study assessed the in vitro activity of AZD0914 against key Gram-positive and fastidious Gram-negative clinical isolates collected globally in 2013. AZD0914 demonstrated potent activity, with MIC90s for AZD0914 of 0.25 mg/liter against Staphylococcus aureus (n = 11,680), coagulase-negative staphylococci (n = 1,923), streptococci (n = 4,380), and Moraxella catarrhalis (n = 145), 0.5 mg/liter against Staphylococcus lugdunensis (n = 120) and Haemophilus influenzae (n = 352), 1 mg/liter against Enterococcus faecalis (n = 1,241), and 2 mg/liter against Haemophilus parainfluenzae (n = 70). The activity against Enterococcus faecium was more limited (MIC90, 8 mg/liter). The spectrum and potency of AZD0914 included fluoroquinolone-resistant isolates in each species group, including methicillin-resistant staphylococci, penicillin-resistant streptococci, vancomycin-resistant enterococci, β-lactamase-producing Haemophilus spp., and M. catarrhalis. Based on these in vitro findings, AZD0914 warrants further investigation for its utility against a variety of Gram-positive and fastidious Gram-negative bacterial species.

• Authors: Douglas J Biedenbach, Michael D Huband, Meredith Hackel, Boudewijn L M de Jonge, Daniel F Sahm, Patricia A Bradford
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 10 Pg. 6053-63 (Oct 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 26195518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Infective Agents
• Barbiturates
• Isoxazoles
• Morpholines
• Oxazolidinones
• Spiro Compounds
• DNA Topoisomerase IV
• DNA Gyrase
• zoliflodacin

Topics

• Anti-Infective Agents (pharmacology)
• Barbiturates (pharmacology)
• DNA Gyrase (metabolism)
• DNA Topoisomerase IV (antagonists & inhibitors)
• Gram-Negative Bacteria (drug effects)
• Gram-Positive Bacteria (drug effects)
• Isoxazoles
• Microbial Sensitivity Tests
• Morpholines
• Oxazolidinones
• Spiro Compounds (pharmacology)