{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T02:15:45Z","timestamp":1773281745071,"version":"3.50.1"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:00:00Z","timestamp":1128124800000},"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":[[2005,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            REP8839 is a novel methionyl-tRNA synthetase (MetS) inhibitor with potent antibacterial activity against clinical isolates of\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            ,\n            <jats:italic>Streptococcus pyogenes<\/jats:italic>\n            , and other clinically important gram-positive bacteria but little activity against gram-negative bacteria. All isolates of\n            <jats:italic>S. aureus<\/jats:italic>\n            , including strains resistant to methicillin, mupirocin, vancomycin, and linezolid were susceptible to REP8839 at concentrations of \u22640.5 \u03bcg\/ml. REP8839 was also active against\n            <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n            , including multiply resistant strains (MIC, \u22640.25 \u03bcg\/ml). All\n            <jats:italic>S. pyogenes<\/jats:italic>\n            isolates were susceptible to REP8839 at concentrations of \u22640.25 \u03bcg\/ml, suggesting that MetS2, a second enzyme previously identified in\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            , was not present in this organism. REP8839 was highly bound to the protein of human serum, and activity was not greatly influenced by inoculum size but was affected by pH, exhibiting optimal antibacterial activity in a neutral medium rather than a weak acidic medium. Like mupirocin, REP8839 exhibited bacteriostatic activity against key pathogens. The emergence of mupirocin resistance in\n            <jats:italic>S. aureus<\/jats:italic>\n            highlights the need for a new topical antibiotic with the ability to inhibit high-level mupirocin-resistant strains and other emerging phenotypes, such as vancomycin-resistant and community-acquired methicillin-resistant isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.49.10.4247-4252.2005","type":"journal-article","created":{"date-parts":[[2005,9,27]],"date-time":"2005-09-27T16:28:08Z","timestamp":1127838488000},"page":"4247-4252","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Antibacterial Activity of REP8839, a New Antibiotic for Topical Use"],"prefix":"10.1128","volume":"49","author":[{"given":"Ian A.","family":"Critchley","sequence":"first","affiliation":[{"name":"Replidyne, Inc., Louisville, Colorado 80027"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casey L.","family":"Young","sequence":"additional","affiliation":[{"name":"Replidyne, Inc., Louisville, Colorado 80027"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberley C.","family":"Stone","sequence":"additional","affiliation":[{"name":"Replidyne, Inc., Louisville, Colorado 80027"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urs A.","family":"Ochsner","sequence":"additional","affiliation":[{"name":"Replidyne, Inc., Louisville, Colorado 80027"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Guiles","sequence":"additional","affiliation":[{"name":"Replidyne, Inc., Louisville, Colorado 80027"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ted","family":"Tarasow","sequence":"additional","affiliation":[{"name":"Replidyne, Inc., Louisville, Colorado 80027"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nebojsa","family":"Janjic","sequence":"additional","affiliation":[{"name":"Replidyne, Inc., Louisville, Colorado 80027"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(98)80085-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050023"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.embor881"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550140037020"},{"key":"e_1_3_2_6_2","first-page":"1123","volume":"282","year":"1999","unstructured":"Centers for Disease Control and Prevention. 1999. 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