Literature DB >> 27499432

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

John R Papp1, Kenneth Lawrence2, Samera Sharpe3, John Mueller2, Robert D Kirkcaldy3.   

Abstract

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. Published by Elsevier B.V.

Entities:  

Keywords:  Antimicrobial susceptibility; Gonorrhoea; Neisseria gonorrhoeae; Novel drug

Mesh：

Substances：

Year:  2016        PMID： 27499432      PMCID： PMC6198316          DOI： 10.1016/j.ijantimicag.2016.05.018

Source DB:  PubMed          Journal:  Int J Antimicrob Agents        ISSN： 0924-8579            Impact factor:   5.283


  10 in total

Review 1.  Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future.

Authors:  Magnus Unemo; William M Shafer
Journal:  Clin Microbiol Rev       Date:  2014-07       Impact factor: 26.132

2.  Inhibition of Neisseria gonorrhoeae Type II Topoisomerases by the Novel Spiropyrimidinetrione AZD0914.

Authors:  Gunther Kern; Tiffany Palmer; David E Ehmann; Adam B Shapiro; Beth Andrews; Gregory S Basarab; Peter Doig; Jun Fan; Ning Gao; Scott D Mills; John Mueller; Shubha Sriram; Jason Thresher; Grant K Walkup
Journal:  J Biol Chem       Date:  2015-07-06       Impact factor: 5.157

3.  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.

Authors:  Magnus Unemo; Johan Ringlander; Catherine Wiggins; Hans Fredlund; Susanne Jacobsson; Michelle Cole
Journal:  Antimicrob Agents Chemother       Date:  2015-06-15       Impact factor: 5.191

4.  Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections.

Authors: 
Journal:  MMWR Morb Mortal Wkly Rep       Date:  2007-04-13       Impact factor: 17.586

5.  Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases.

Authors:  Gregory S Basarab; Gunther H Kern; John McNulty; John P Mueller; Kenneth Lawrence; Karthick Vishwanathan; Richard A Alm; Kevin Barvian; Peter Doig; Vincent Galullo; Humphrey Gardner; Madhusudhan Gowravaram; Michael Huband; Amy Kimzey; Marshall Morningstar; Amy Kutschke; Sushmita D Lahiri; Manos Perros; Renu Singh; Virna J A Schuck; Ruben Tommasi; Grant Walkup; Joseph V Newman
Journal:  Sci Rep       Date:  2015-07-14       Impact factor: 4.379

6.  Characterization of the novel DNA gyrase inhibitor AZD0914: low resistance potential and lack of cross-resistance in Neisseria gonorrhoeae.

Authors:  Richard A Alm; Sushmita D Lahiri; Amy Kutschke; Linda G Otterson; Robert E McLaughlin; James D Whiteaker; Lisa A Lewis; Xiaohong Su; Michael D Huband; Humphrey Gardner; John P Mueller
Journal:  Antimicrob Agents Chemother       Date:  2014-12-22       Impact factor: 5.191

7.  Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011.

Authors:  Catherine A Ison; Katy Town; Chinelo Obi; Stephanie Chisholm; Gwenda Hughes; David M Livermore; Catherine M Lowndes
Journal:  Lancet Infect Dis       Date:  2013-06-11       Impact factor: 25.071

8.  Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates.

Authors:  R J Belland; S G Morrison; C Ison; W M Huang
Journal:  Mol Microbiol       Date:  1994-10       Impact factor: 3.501

9.  Trends in Neisseria gonorrhoeae Susceptibility to Cephalosporins in the United States, 2006-2014.

Authors:  Robert D Kirkcaldy; Edward W Hook; Olusegun O Soge; Carlos del Rio; Grace Kubin; Jonathan M Zenilman; John R Papp
Journal:  JAMA       Date:  2015-11-03       Impact factor: 56.272

10.  Genetic Resistance Determinants, In Vitro Time-Kill Curve Analysis and Pharmacodynamic Functions for the Novel Topoisomerase II Inhibitor ETX0914 (AZD0914) in Neisseria gonorrhoeae.

Authors:  Sunniva Foerster; Daniel Golparian; Susanne Jacobsson; Lucy J Hathaway; Nicola Low; William M Shafer; Christian L Althaus; Magnus Unemo
Journal:  Front Microbiol       Date:  2015-12-10       Impact factor: 5.640
  10 in total
  5 in total

1.  High in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among consecutive clinical Neisseria gonorrhoeae isolates from Thailand (2018) and South Africa (2015-2017).

Authors:  Susanne Jacobsson; Ranmini Kularatne; Rossaphorn Kittiyaowamarn; Venessa Maseko; Porntip Paopang; Pongsathorn Sangprasert; Pachara Sirivongrangson; Laura Piddock; Teodora Wi; Emilie Alirol; Magnus Unemo
Journal:  Antimicrob Agents Chemother       Date:  2019-09-23       Impact factor: 5.191

2.  Evaluation of apramycin against spectinomycin-resistant and -susceptible strains of Neisseria gonorrhoeae.

Authors:  Stefan Riedel; Divya Vijayakumar; Gretchen Berg; Anthony D Kang; Kenneth P Smith; James E Kirby
Journal:  J Antimicrob Chemother       Date:  2019-05-01       Impact factor: 5.790

3.  Single-Dose Pharmacokinetics, Excretion, and Metabolism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic, in Healthy Volunteers.

Authors:  John O'Donnell; Ken Lawrence; Karthick Vishwanathan; Vinayak Hosagrahara; John P Mueller
Journal:  Antimicrob Agents Chemother       Date:  2018-12-21       Impact factor: 5.191

4.  Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.

Authors:  Anthony D Cristillo; Claire C Bristow; Elizabeth Torrone; Jo-Anne Dillon; Robert D Kirkcaldy; Huan Dong; Yonatan H Grad; Robert A Nicholas; Peter A Rice; Kenneth Lawrence; David Oldach; William Maurice Shafer; Pei Zhou; Teodora E Wi; Sheldon R Morris; Jeffrey D Klausner
Journal:  Sex Transm Dis       Date:  2019-03       Impact factor: 2.830

Review 5.  Epidemiology, Treatments, and Vaccine Development for Antimicrobial-Resistant Neisseria gonorrhoeae: Current Strategies and Future Directions.

Authors:  Eric Y Lin; Paul C Adamson; Jeffrey D Klausner
Journal:  Drugs       Date:  2021-06-07       Impact factor: 9.546
  5 in total

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