{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:49:21Z","timestamp":1787320161451,"version":"build-2736575974"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"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":[[2008,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We present data from antimicrobial assays performed in vitro that pertain to the potential clinical utility of a novel rifamycin-quinolone hybrid antibiotic, CBR-2092, for the treatment of infections mediated by gram-positive cocci. The MIC\n                    <jats:sub>90<\/jats:sub>\n                    s for CBR-2092 against 300 clinical isolates of staphylococci and streptococci ranged from 0.008 to 0.5 \u03bcg\/ml. Against\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , CBR-2092 exhibited prolonged postantibiotic effects (PAEs) and sub-MIC effects (SMEs), with values of 3.2, 6.5, and &gt;8.5 h determined for the PAE (3\u00d7 MIC), SME (0.12\u00d7 MIC), and PAE-SME (3\u00d7 MIC\/0.12\u00d7 MIC) periods, respectively. Studies of genetically defined mutants of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    indicate that CBR-2092 is not a substrate for the NorA or MepA efflux pumps. In minimal bactericidal concentration and time-kill studies, CBR-2092 exhibited bactericidal activity against staphylococci that was retained against rifampin- or intermediate quinolone-resistant strains, with apparent paradoxical cidal characteristics against rifampin-resistant strains. In spontaneous resistance studies, CBR-2092 exhibited activity consistent with balanced contributions from its composite pharmacophores, with a mutant prevention concentration of 0.12 \u03bcg\/ml and a resistance frequency of &lt;10\n                    <jats:sup>\u221212<\/jats:sup>\n                    determined at 1 \u03bcg\/ml in agar for\n                    <jats:italic>S. aureus<\/jats:italic>\n                    . Similarly, CBR-2092 suppressed the emergence of preexisting rifamycin resistance in time-kill studies undertaken at a high cell density. In studies of the intracellular killing of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , CBR-2092 exhibited prolonged bactericidal activity that was superior to the activities of moxifloxacin, rifampin, and a cocktail of moxifloxacin and rifampin. Overall, CBR-2092 exhibited promising activity in a range of antimicrobial assays performed in vitro that pertain to properties relevant to the effective treatment of serious infections mediated by gram-positive cocci.\n                  <\/jats:p>","DOI":"10.1128\/aac.01651-07","type":"journal-article","created":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T20:53:45Z","timestamp":1209416025000},"page":"2324-2334","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Microbiology Profiling Studies with Staphylococci and Streptococci"],"prefix":"10.1128","volume":"52","author":[{"given":"Gregory T.","family":"Robertson","sequence":"first","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Bonventre","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Du","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Duncan","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Morris","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Roche","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalai","family":"Yan","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Simon","family":"Lynch","sequence":"additional","affiliation":[{"name":"Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, Texas 75235-2304"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.2.335"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2005.05.005"},{"key":"e_1_3_2_4_2","unstructured":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically approved standard 7th ed. 2006 vol. 26"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00430-07"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg269"},{"key":"e_1_3_2_7_2","first-page":"19","year":"2003","unstructured":"Drlica, K., and D. C. Hooper. 2003. Mechanisms of quinolone action, p. 19-40. In D. C. Hooper and E. Rubinstein (ed.), Quinolone antimicrobial agents, 3rd ed. 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