Biedenbach, Douglas J.;
Huband, Michael D.;
Hackel, Meredith;
de Jonge, Boudewijn L. M.;
Sahm, Daniel F.;
Bradford, Patricia A.
In Vitro Activity of AZD0914, a Novel Bacterial DNA Gyrase/Topoisomerase IV Inhibitor, against Clinically Relevant Gram-Positive and Fastidious Gram-Negative Pathogens
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Media type:
E-Article
Title:
In Vitro Activity of AZD0914, a Novel Bacterial DNA Gyrase/Topoisomerase IV Inhibitor, against Clinically Relevant Gram-Positive and Fastidious Gram-Negative Pathogens
Contributor:
Biedenbach, Douglas J.;
Huband, Michael D.;
Hackel, Meredith;
de Jonge, Boudewijn L. M.;
Sahm, Daniel F.;
Bradford, Patricia A.
Published:
American Society for Microbiology, 2015
Published in:
Antimicrobial Agents and Chemotherapy, 59 (2015) 10, Seite 6053-6063
Language:
English
DOI:
10.1128/aac.01016-15
ISSN:
0066-4804;
1098-6596
Origination:
Footnote:
Description:
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 MIC 90 s 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 (MIC 90 , 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.