{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T10:05:22Z","timestamp":1775297122071,"version":"3.50.1"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            ACH-702, a novel isothiazoloquinolone (ITQ), was assessed for antibacterial activity against a panel of Gram-positive and Gram-negative clinical isolates and found to possess broad-spectrum activity, especially against antibiotic-resistant Gram-positive strains, including methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            (MRSA). For Gram-negative bacteria, ACH-702 showed exceptional potency against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Haemophilus influenzae<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Moraxella catarrhalis<\/jats:named-content>\n            , and a\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria<\/jats:named-content>\n            sp. but was less active against members of the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacteriaceae<\/jats:named-content>\n            . Good antibacterial activity was also evident against several anaerobes as well as\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Legionella pneumophila<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycoplasma pneumoniae<\/jats:named-content>\n            . Excellent bactericidal activity was observed for ACH-702 against several bacterial pathogens in time-kill assays, and postantibiotic effects (PAEs) of &gt;1 h were evident with both laboratory and clinical strains of staphylococci at 10\u00d7 MIC and similar in most cases to those observed for moxifloxacin at the same MIC multiple.\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">In vivo<\/jats:named-content>\n            efficacy was demonstrated against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            with murine sepsis and thigh infection models, with decreases in the number of CFU\/thigh equal to or greater than those observed after vancomycin treatment. Macromolecular synthesis assays showed specific dose-dependent inhibition of DNA replication in staphylococci, and biochemical analyses indicated potent dual inhibition of two essential DNA replication enzymes: DNA gyrase and topoisomerase IV. Additional biological data in support of an effective dual targeting mechanism of action include the following: low MIC values (\u22640.25 \u03bcg\/ml) against staphylococcal strains with single mutations in both\n            <jats:italic>gyrA<\/jats:italic>\n            and\n            <jats:italic>grlA<\/jats:italic>\n            (\n            <jats:italic>parC<\/jats:italic>\n            ), retention of good antibacterial activity (MICs of \u22640.5 \u03bcg\/ml) against staphylococcal strains with two mutations in both\n            <jats:italic>gyrA<\/jats:italic>\n            and\n            <jats:italic>grlA<\/jats:italic>\n            , and low frequencies for the selection of higher-level resistance (&lt;10\n            <jats:sup>\u221210<\/jats:sup>\n            ). These promising initial data support further study of isothiazoloquinolones as potential clinical candidates.\n          <\/jats:p>","DOI":"10.1128\/aac.01666-10","type":"journal-article","created":{"date-parts":[[2011,4,5]],"date-time":"2011-04-05T03:18:51Z","timestamp":1301973531000},"page":"2860-2871","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["In Vitro and In Vivo Profiles of ACH-702, an Isothiazoloquinolone, against Bacterial Pathogens"],"prefix":"10.1128","volume":"55","author":[{"given":"Michael J.","family":"Pucci","sequence":"first","affiliation":[{"name":"Achillion Pharmaceuticals, New Haven, Connecticut 06511"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven D.","family":"Podos","sequence":"additional","affiliation":[{"name":"Achillion Pharmaceuticals, New Haven, Connecticut 06511"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane A.","family":"Thanassi","sequence":"additional","affiliation":[{"name":"Achillion Pharmaceuticals, New Haven, Connecticut 06511"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa J.","family":"Leggio","sequence":"additional","affiliation":[{"name":"Achillion Pharmaceuticals, New Haven, Connecticut 06511"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barton J.","family":"Bradbury","sequence":"additional","affiliation":[{"name":"Achillion Pharmaceuticals, New Haven, Connecticut 06511"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milind","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Achillion Pharmaceuticals, New Haven, Connecticut 06511"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/24.Supplement_1.S67"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01344.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp0804651"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.8.3325-3333.2005"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550140037020"},{"key":"e_1_3_2_8_2","first-page":"2116","article-title":"Vancomycin resistant Staphylococcus aureus\u2014Pennsylvania, 2002","volume":"288","author":"Centers for Disease Control and Prevention","year":"2002","unstructured":"Centers for Disease Control and Prevention. 2002. 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