High
            <i>In Vitro</i>
            Susceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 2014

Unemo, Magnus; Ringlander, Johan; Wiggins, Catherine; Fredlund, Hans; Jacobsson, Susanne; Cole, Michelle

doi:10.1128/aac.00786-15

Cited by 46 publications

(39 citation statements)

References 25 publications

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“…Initially, a high in vitro susceptibility of ETX0914 was verified against a panel of 250 temporally, geographically and genetically diverse N. gonorrhoeae isolates, which included a high proportion of fluoroquinolone-, ESC- and multidrug-resistant isolates (158). It has now also been shown that the ETX0914 susceptibility among 873 contemporary clinical gonococcal isolates from 21 countries in the European Union/European Economic Area countries is exceedingly high and no ETX0914 resistance has yet been indentified (160). Currently, a multi-centre, open-label, randomized Phase 2 clinical ETX014 trial is running.…”

Section: Future Treatments For Gonorrheamentioning

confidence: 99%

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae : A Major Global Public Health Problem in the 21st Century

2016

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Neisseria gonorrhoeae is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea. Unfortunately, the gonococcus developed decreased susceptibility or even resistance to these initially employed antibiotics, a trend that continued over subsequent decades with each new antibiotic that was brought into clinical practice. As this pattern of resistance has continued into the 21st century, there is now reason for great concern, especially in an era when few new antibiotics have prospects for use as treatment of gonorrhea. Here, we review the history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance, and prospects for future treatment regimens in the 21st century.

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Section: Future Treatments For Gonorrheamentioning

confidence: 99%

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae : A Major Global Public Health Problem in the 21st Century

2016

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“…In addition to lower MICs, ETX0914 is administered orally, which compares favourably with the need for intramuscular injection of ceftriaxone. A previous study reported that ETX0914 was effective against N. gonorrhoeae growth using a panel of European isolates [19]. Collectively, ETX0914 may be an international option for the treatment of gonorrhoea and is currently in a phase 2 clinical trial.…”

Section: Discussionmentioning

confidence: 99%

“…Although ETX0914 has a similar mechanism of action as ciprofloxacin in targeting DNA gyrase, the binding modes are sufficiently distinct [11] that ciprofloxacin-resistant isolates are highly susceptible to ETX0914. ETX0914 shows promise for treatment of gonococcal infections, including ciprofloxacin-resistant infections, and particularly as part of combination therapy with a second antimicrobial agent [19,20]. …”

Section: Discussionmentioning

confidence: 99%

In vitro growth of multidrug-resistant Neisseria gonorrhoeae isolates is inhibited by ETX0914, a novel spiropyrimidinetrione

Papp

Lawrence

Sharpe

et al. 2016

International Journal of Antimicrobial Agents

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Antimicrobial resistance in Neisseria gonorrhoeae has severely limited the number of treatment options, and the emergence of extended-spectrum cephalosporin resistance threatens the effectiveness of the last remaining recommended treatment regimen. This study assessed the in vitro susceptibility of N. gonorrhoeae to ETX0914, a novel spiropyrimidinetrione that inhibits DNA biosynthesis. In vitro activity was determined by agar dilution against 100 N. gonorrhoeae isolates collected from men presenting with urethritis in the USA during 2012–2013 through the Gonococcal Isolate Surveillance Project. The minimum inhibitory concentration (MIC) that inhibited growth in 50% (MIC50) and 90% (MIC90) of isolates was calculated for each antimicrobial agent. ETX0914 demonstrated a high level of antimicrobial activity against N. gonorrhoeae, including isolates with decreased susceptibility or resistance to currently available agents. The ability of ETX0914 to inhibit the growth of N. gonorrhoeae was similar to ceftriaxone, which is currently recommended in combination with azithromycin to treat gonorrhoea. The data presented in this study strongly suggest that ETX0914 should be evaluated in a clinical trial for the treatment of N. gonorrhoeae.

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“…30) was found to be active against S. pneumoniae ParE (IC 50 respectively. In another studies [114][115][116] this compound exhibited Gram-positive spectrum along with activity against fastidious Gram-negative bacteria, and anaerobes including Neisseria gonorrhoeae with low resistance potential. AZD0914 exhibited high activity when tested against Kibdelomycin (77a, Fig.…”

Section: A-hmentioning

confidence: 97%

Dual targeting DNA gyrase B (GyrB) and topoisomerse IV (ParE) inhibitors: A review

Azam

Thathan

Selvaraj

2015

Bioorganic Chemistry

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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

Cited by 46 publications

References 25 publications

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae : A Major Global Public Health Problem in the 21st Century

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae : A Major Global Public Health Problem in the 21st Century

In vitro growth of multidrug-resistant Neisseria gonorrhoeae isolates is inhibited by ETX0914, a novel spiropyrimidinetrione

Dual targeting DNA gyrase B (GyrB) and topoisomerse IV (ParE) inhibitors: A review

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