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

Autor:	Biedenbach DJ; International Health Management Associates, Inc., Schaumburg, Illinois, USA dbiedenbach@ihmainc.com., Huband MD; AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA., Hackel M; International Health Management Associates, Inc., Schaumburg, Illinois, USA., de Jonge BL; AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA., Sahm DF; International Health Management Associates, Inc., Schaumburg, Illinois, USA., Bradford PA; AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2015 Oct; Vol. 59 (10), pp. 6053-63. Date of Electronic Publication: 2015 Jul 20.
DOI:	10.1128/AAC.01016-15
Abstrakt:	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. (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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