{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:02:27Z","timestamp":1773046947985,"version":"3.50.1"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[1997,10,1]],"date-time":"1997-10-01T00:00:00Z","timestamp":875664000000},"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":[[1997,10]]},"abstract":"<jats:p>The in vivo activity of BO-3482, which has a dithiocarbamate chain at the C-2 position of 1beta-methyl-carbapenem, was compared with those of vancomycin and imipenem in murine models of septicemia and thigh infection with methicillin-resistant Staphylococcus aureus (MRSA). Because BO-3482 was more susceptible than imipenem to renal dehydropeptidase I in a kinetic study of hydrolysis by this renal enzyme, the therapeutic efficacy of BO-3482 was determined during coadministration with cilastatin. In the septicemia models, which involved two homogeneous MRSA strains and one heterogeneous MRSA strain, the 50% effective doses were, respectively, 4.80, 6.06, and 0.46 mg\/kg of body weight for BO-3482; 5.56, 2.15, and 1.79 mg\/kg for vancomycin; and &gt;200, &gt;200, and 15.9 mg\/kg for imipenem. BO-3482 was also as effective as vancomycin in an MRSA septicemia model with mice with cyclophosphamide-induced immunosuppression. In the thigh infection model with a homogeneous MRSA strain, the bacterial counts in tissues treated with BO-3482-cilastatin were significantly reduced in a dose-dependent manner compared with the counts in those treated with vancomycin and imipenem-cilastatin (P &lt; 0.001). These results indicate that BO-3482-cilastatin is as effective as vancomycin in murine systemic infections and is more bactericidal than vancomycin in local-tissue infections. The potent in vivo activity of BO-3482-cilastatin against such MRSA infections can be ascribed to the good in vitro anti-MRSA activity and improved pharmacokinetics in mice when BO-3482 is combined with cilastatin and to the bactericidal nature of the carbapenem.<\/jats:p>","DOI":"10.1128\/aac.41.10.2278","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:27:03Z","timestamp":1539044823000},"page":"2278-2281","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Therapeutic efficacy of BO-3482, a novel dithiocarbamate carbapenem, in mice infected with methicillin-resistant Staphylococcus aureus"],"prefix":"10.1128","volume":"41","author":[{"given":"R","family":"Nagano","sequence":"first","affiliation":[{"name":"Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Shibata","sequence":"additional","affiliation":[{"name":"Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Naito","sequence":"additional","affiliation":[{"name":"Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Fuse","sequence":"additional","affiliation":[{"name":"Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Asano","sequence":"additional","affiliation":[{"name":"Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.41.10.2278","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.41.10.2278","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:10:53Z","timestamp":1645474253000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.41.10.2278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,10]]},"references-count":0,"journal-issue":{"issue":"10","published-print":{"date-parts":[[1997,10]]}},"alternative-id":["10.1128\/AAC.41.10.2278"],"URL":"https:\/\/doi.org\/10.1128\/aac.41.10.2278","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,10]]},"assertion":[{"value":"1997-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}