title: In vitro growth of multidrug-resistant Neisseria gonorrhoeae isolates is inhibited by ETX0914, a novel spiropyrimidinetrione.
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.
authors: US Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA. Electronic address: jwp6@cdc.gov.
authors: John R
authors: JR
authors: Papp
authors: Entasis Therapeutics, 35 Gatehouse Drive Suite E0, Waltham, MA 02451, USA.
authors: Kenneth
authors: K
authors: Lawrence
authors: US Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
authors: Samera
authors: S
authors: Sharpe
authors: Entasis Therapeutics, 35 Gatehouse Drive Suite E0, Waltham, MA 02451, USA.
authors: John
authors: J
authors: Mueller
authors: US Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
authors: Robert D
authors: RD
authors: Kirkcaldy
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006069:Gonorrhea / Q000382:microbiology; D006801:Humans; D007555:Isoxazoles; D008297:Male; D008826:Microbial Sensitivity Tests; D009025:Morpholines; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000254:growth & development* / Q000302:isolation & purification; D023303:Oxazolidinones; D013141:Spiro Compounds / Q000494:pharmacology*; D014481:United States; D014526:Urethritis / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001463:Barbiturates; D007555:Isoxazoles; D009025:Morpholines; D023303:Oxazolidinones; D013141:Spiro Compounds; C000599190:zoliflodacin
keywords: Antimicrobial susceptibility; Gonorrhoea; Neisseria gonorrhoeae; Novel drug