{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:20Z","timestamp":1791414140542,"version":"4.3.3"},"reference-count":16,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HHS | Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority","award":["HHSO100201300011C"],"award-info":[{"award-number":["HHSO100201300011C"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has\n in vitro<\/jats:italic>\n activity against susceptible and drug-resistant pathogens. Reference\n in vitro<\/jats:italic>\n methods were used to investigate the MICs and minimum bactericidal concentrations (MBCs) of gepotidacin and comparator agents for\n Staphylococcus aureus<\/jats:named-content>\n ,\n Streptococcus pneumoniae<\/jats:named-content>\n , and\n Escherichia coli<\/jats:named-content>\n . Gepotidacin\n in vitro<\/jats:italic>\n activity was also evaluated by using time-kill kinetics and broth microdilution checkerboard methods for synergy testing and for postantibiotic and subinhibitory effects. The MIC\n 90<\/jats:sub>\n of gepotidacin for 50\n S. aureus<\/jats:named-content>\n (including methicillin-resistant\n S. aureus<\/jats:named-content>\n [MRSA]) and 50\n S. pneumoniae<\/jats:named-content>\n (including penicillin-nonsusceptible) isolates was 0.5 \u03bcg\/ml, and for\n E. coli<\/jats:named-content>\n (\n n<\/jats:italic>\n = 25 isolates), it was 4 \u03bcg\/ml. Gepotidacin was bactericidal against\n S. aureus<\/jats:named-content>\n ,\n S. pneumoniae<\/jats:named-content>\n , and\n E. coli<\/jats:named-content>\n , with MBC\/MIC ratios of \u22644 against 98, 98, and 88% of the isolates tested, respectively. Time-kill curves indicated that the bactericidal activity of gepotidacin was observed at 4\u00d7 or 10\u00d7 MIC at 24 h for all of the isolates.\n S. aureus<\/jats:named-content>\n regrowth was observed in the presence of gepotidacin, and the resulting gepotidacin MICs were 2- to 128-fold higher than the baseline gepotidacin MICs. Checkerboard analysis of gepotidacin combined with other antimicrobials demonstrated no occurrences of antagonism with agents from multiple antimicrobial classes. The most common interaction when testing gepotidacin was indifference (fractional inhibitory concentration index of >0.5 to \u22644; 82.7% for Gram-positive isolates and 82.6% for Gram-negative isolates). The postantibiotic effect (PAE) of gepotidacin was short when it was tested against\n S. aureus<\/jats:named-content>\n (\u22640.6 h against MRSA and MSSA), and the PAE\u2013sub-MIC effect (SME) was extended (>8 h; three isolates at 0.5\u00d7 MIC). The PAE of levofloxacin was modest (0.0 to 2.4 h), and the PAE-SME observed varied from 1.2 to >9 h at 0.5\u00d7 MIC. These\n in vitro<\/jats:italic>\n data indicate that gepotidacin is a bactericidal agent that exhibits a modest PAE and an extended PAE-SME against Gram-positive and -negative bacteria and merits further study for potential use in treating infections caused by these pathogens.\n <\/jats:p>","DOI":"10.1128\/aac.00468-17","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T20:40:16Z","timestamp":1494276016000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":74,"title":["Gepotidacin (GSK2140944)\n In Vitro<\/i>\n Activity against Gram-Positive and Gram-Negative Bacteria"],"prefix":"10.1128","volume":"61","author":[{"given":"R. K.","family":"Flamm","sequence":"first","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Farrell","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Rhomberg","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. E.","family":"Scangarella-Oman","sequence":"additional","affiliation":[{"name":"GSK, Collegeville, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. S.","family":"Sader","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09197"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02820-15"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00527-16"},{"key":"e_1_3_3_5_2","volume-title":"ASM Microbe","author":"Flamm RK","year":"2016","unstructured":"Flamm RK SaderHS RhombergPR Scangarella-OmanNE FarrellDJ. 2016. Gepotidacin (GSK2140944) in vitro activity against Gram-positive and Gram-negative bacteria (MBC\/MIC, kill kinetics, checkerboard, PAE\/SME tests), abstr 460. ASM Microbe, Boston, MA, 16 to 20 June 2016."},{"key":"e_1_3_3_6_2","volume-title":"ASM Microbe","author":"Farrell DJ","year":"2016","unstructured":"Farrell DJ SaderHS RhombergPR Scangarella-OmanNE FlammRK. 2016. Gepotidacin (GSK2140944) in vitro activity against Neisseria gonorrhoeae (MIC\/MBC, kill kinetics, checkerboard, PAE\/SME tests), abstr 461. ASM Microbe, Boston, MA, 16 to 20 June 2016."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00571-15"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04077-14"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02778-13"},{"key":"e_1_3_3_10_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard\u2014tenth edition","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. M07-A10. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard\u2014tenth edition. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_11_2","volume-title":"Methods for determining bactericidal activity of antimicrobial agents; approved guideline","author":"Clinical and Laboratory Standards Institute","year":"1999","unstructured":"Clinical and Laboratory Standards Institute. 1999. M26-A. Methods for determining bactericidal activity of antimicrobial agents; approved guideline. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_12_2","volume-title":"Performance standards for antimicrobial susceptibility testing; 26th informational supplement","author":"Clinical and Laboratory Standards Institute","year":"2016","unstructured":"Clinical and Laboratory Standards Institute. 2016. M100-S26. Performance standards for antimicrobial susceptibility testing; 26th informational supplement. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_13_2","volume-title":"Clinical microbiology procedures handbook","author":"Koeth LM","year":"2016","unstructured":"Koeth LM . 2016. Tests to assess bactericidal activity. InLeberAL (ed), Clinical microbiology procedures handbook, 4th ed, vol 2. ASM Press, Washington, DC.","edition":"4"},{"key":"e_1_3_3_14_2","first-page":"5.12.11","volume-title":"Clinical microbiology procedures handbook","author":"Moody J","year":"2004","unstructured":"Moody J . 2004. Susceptibility tests to evaluate synergism, p 5.12.11\u201315.12.23. InIsenbergHD (ed), Clinical microbiology procedures handbook, vol 5. ASM Press, Washington, DC."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/31.6.881"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.9.1852"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.5.1253"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00468-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00468-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:07:26Z","timestamp":1645459646000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00468-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":16,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1128\/AAC.00468-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00468-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]},"assertion":[{"value":"2017-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00468-17"}}