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High In Vitro Susceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 2014
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria; Department of Laboratory Medicine, Clinical Microbiology.
WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro, Sweden.
Sexually Transmitted Bacteria Reference Unit, Public Health England, Colindale, London, United Kingdom.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria; Department of Laboratory Medicine, Clinical Microbiology .
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2015 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, no 9, 5220-5225 p.Article in journal (Refereed) Published
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Abstract [en]

Resistance in Neisseria gonorrhoeae against all antimicrobials available for the treatment of gonorrhea has emerged. The first gonococcal strains with high-level resistance to ceftriaxone, the last option for first-line empirical antimicrobial monotherapy, were recently described. Consequently, new treatment options are essential. In this study, the in vitro activity of the novel spiropyrimidinetrione ETX0914 (AZD0914), a DNA topoisomerase II inhibitor, was investigated among contemporary consecutive clinical N. gonorrhoeae isolates obtained in 21 European countries and compared to the activities of antimicrobials currently or previously recommended for treatment. Consecutive clinical N. gonorrhoeae isolates (n = 873) cultured in 21 European countries from 2012 to 2014 were examined for their susceptibility to ETX0914. The MICs of ETX0914 were determined using the agar dilution method. For comparison, the MICs of ceftriaxone, cefixime, azithromycin, and ciprofloxacin were determined using Etest or the agar dilution method. For ETX0914, the MIC range, modal MIC, MIC50, and MIC90 were <= 0.002 to 0.25 mg/liter, 0.125 mg/liter, 0.064 mg/liter, and 0.125 mg/liter, respectively. The MIC values were substantially lower than those of the fluoroquinolone ciprofloxacin and most other antimicrobials examined. No cross-resistance with any other examined antimicrobial was observed. In conclusion, the in vitro susceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical isolates from 21 European countries was high, and no cross-resistance to antimicrobials currently or previously used for gonorrhea treatment was indicated. Additional studies investigating the in vitro and in vivo induction and mechanisms of ETX0914 resistance in gonococci, pharmacokinetics/pharmacodynamics in modeling/simulations and in humans, and performance in randomized controlled gonorrhea treatment trials are essential.

Place, publisher, year, edition, pages
American Society for Microbiology , 2015. Vol. 59, no 9, 5220-5225 p.
National Category
Microbiology in the medical area Pharmacology and Toxicology
Research subject
Microbiology
Identifiers
URN: urn:nbn:se:oru:diva-47016DOI: 10.1128/AAC.00786-15ISI: 000364343900017PubMedID: 26077246Scopus ID: 2-s2.0-84940951189OAI: oai:DiVA.org:oru-47016DiVA: diva2:878517
Note

Funding Agencies:

Örebro County Council Research Committee

Foundation for Medical Research at Örebro University Hospital, Sweden

Available from: 2015-12-09 Created: 2015-12-09 Last updated: 2017-03-21Bibliographically approved

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Unemo, MagnusFredlund, HansJacobsson, Susanne
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CiteExportLink to record
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