{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:08:29Z","timestamp":1761487709577},"reference-count":26,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T00:00:00Z","timestamp":1162339200000},"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":[[2006,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Novel rifamycins (new chemical entities [NCEs]) having MICs of 0.002 to 0.03 \u03bcg\/ml against\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            and retaining some activity against rifampin-resistant mutants were tested for in vivo efficacy against susceptible and rifampin-resistant strains of\n            <jats:italic>S. aureus<\/jats:italic>\n            . Rifalazil and rifampin had a 50% effective dose (ED\n            <jats:sub>50<\/jats:sub>\n            ) of 0.06 mg\/kg of body weight when administered as a single intravenous (i.v.) dose in a murine septicemia model against a susceptible strain of\n            <jats:italic>S. aureus.<\/jats:italic>\n            The majority of NCEs showed efficacy at a lower i.v. dose (0.003 to 0.06 mg\/kg). In addition, half of the NCEs tested for oral efficacy had ED\n            <jats:sub>50<\/jats:sub>\n            s in the range of 0.015 to 0.13 mg\/kg, i.e., lower or equivalent to the oral ED\n            <jats:sub>50<\/jats:sub>\n            s of rifampin and rifalazil. NCEs were also tested in the septicemia model against a rifampin-resistant strain of\n            <jats:italic>S. aureus<\/jats:italic>\n            . Twenty-four of 169 NCEs were efficacious when administered as a single oral dose of 80 mg\/kg. These NCEs were examined in the murine thigh infection model against a susceptible strain of\n            <jats:italic>S. aureus<\/jats:italic>\n            . Several NCEs dosed by intraperitoneal injection at 0.06 mg\/kg caused a significant difference in bacterial titer compared with placebo-treated animals. No NCEs showed efficacy in the thigh model against a highly rifampin-resistant strain. However, several NCEs showed an effect when tested against a partially rifampin-resistant strain. The NCEs having a 25-hydroxyl moiety were more effective as a group than their 25-\n            <jats:italic>O<\/jats:italic>\n            -acetyl counterparts. These model systems defined candidate NCEs as components of potential combination therapies to treat systemic infections or as monotherapeutic agents for topical applications.\n          <\/jats:p>","DOI":"10.1128\/aac.01087-05","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T20:58:50Z","timestamp":1161809930000},"page":"3658-3664","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Efficacy of Novel Rifamycin Derivatives against Rifamycin-Sensitive and -Resistant\n            <i>Staphylococcus aureus<\/i>\n            Isolates in Murine Models of Infection"],"prefix":"10.1128","volume":"50","author":[{"given":"David\u2009M.","family":"Rothstein","sequence":"first","affiliation":[{"name":"ActivBiotics, Inc., 110 Hartwell Avenue, Lexington, Massachusetts 02421"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald S.","family":"Farquhar","sequence":"additional","affiliation":[{"name":"ActivBiotics, Inc., 110 Hartwell Avenue, Lexington, Massachusetts 02421"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klari","family":"Sirokman","sequence":"additional","affiliation":[{"name":"Gwathmey, Inc., 763 Building E, Concord Avenue, Cambridge, Massachusetts 01238"},{"name":"Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Sondergaard","sequence":"additional","affiliation":[{"name":"Gwathmey, Inc., 763 Building E, Concord Avenue, Cambridge, Massachusetts 01238"},{"name":"Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Hazlett","sequence":"additional","affiliation":[{"name":"Gwathmey, Inc., 763 Building E, Concord Avenue, Cambridge, Massachusetts 01238"},{"name":"Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelia A.","family":"Doye","sequence":"additional","affiliation":[{"name":"Gwathmey, Inc., 763 Building E, Concord Avenue, Cambridge, Massachusetts 01238"},{"name":"Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith K.","family":"Gwathmey","sequence":"additional","affiliation":[{"name":"Gwathmey, Inc., 763 Building E, Concord Avenue, Cambridge, Massachusetts 01238"},{"name":"Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Mullin","sequence":"additional","affiliation":[{"name":"ActivBiotics, Inc., 110 Hartwell Avenue, Lexington, Massachusetts 02421"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"van Duzer","sequence":"additional","affiliation":[{"name":"ActivBiotics, Inc., 110 Hartwell Avenue, Lexington, Massachusetts 02421"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher K.","family":"Murphy","sequence":"additional","affiliation":[{"name":"ActivBiotics, Inc., 110 Hartwell Avenue, Lexington, Massachusetts 02421"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.5.1072"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.10.3975-3979.2004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.5.1571-1573.2002"},{"key":"e_1_3_2_5_2","first-page":"752","year":"1991","unstructured":"Cleeland, R., and E. 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