{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T18:18:52Z","timestamp":1759342732168},"reference-count":0,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1995,2,1]],"date-time":"1995-02-01T00:00:00Z","timestamp":791596800000},"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":[[1995,2]]},"abstract":"<jats:p>L-695,256 is a synthetic carbapenem beta-lactam antibiotic that binds with a high degree of affinity to penicillin-binding protein (PBP) PBP 2a, the protein that mediates staphylococcal resistance to methicillin. The concentration of L-695,256 that inhibited binding of radiolabeled [3H]penicillin to PBP 2a by 50% was 1.2 micrograms\/ml, whereas they were 14 and 68 micrograms\/ml for penicillin and imipenem, respectively. Cell wall synthesis, determined by incorporation of [14C]N-acetylglucosamine into whole cells, was inhibited by 50% at concentrations of 1.3, 26, and 132 micrograms\/ml for L-695,256, penicillin, and imipenem, respectively, for the methicillin-resistant strain COL. Growth of cells of each of two homogeneously resistant strains, COL and 76, was completely inhibited by 4 micrograms of L-695,256 per ml, whereas growth was inhibited by 100 micrograms or more of penicillin or imipenem per ml. The efficacies of L-695,256 (10 mg\/kg given three times daily [t.i.d.]), imipenem (37.5 mg\/kg t.i.d.), penicillin (300,000 units\/kg t.i.d.), and vancomycin (25 mg\/kg given twice daily) were compared in the rabbit model of aortic valve endocarditis established with these homogeneous strains. After 4 days of treatment, mean bacterial densities in aortic valve vegetations were reduced by 4.0 to 5.8 log10 CFU\/g for L-695,256, 1.0 to 1.8 log10 CFU\/g for imipenem, -1.1 to 3.9 log10 CFU\/g for penicillin, and 1.1 to 3.0 log10 CFU\/g for vancomycin in comparison to the densities of controls. Compounds such as L-695,256 that are bound by PBP 2a with a high degree of affinity are likely to be extremely effective in the treatment of infections caused by methicillin-resistant staphylococci.<\/jats:p>","DOI":"10.1128\/aac.39.2.462","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:06:25Z","timestamp":1340841985000},"page":"462-466","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["In vitro and in vivo antistaphylococcal activities of L-695,256, a carbapenem with high affinity for the penicillin-binding protein PBP 2a"],"prefix":"10.1128","volume":"39","author":[{"given":"H F","family":"Chambers","sequence":"first","affiliation":[{"name":"Medical Service, San Francisco General Hospital, California, USA."}],"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.39.2.462","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.2.462","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:06:27Z","timestamp":1645473987000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.39.2.462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,2]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1995,2]]}},"alternative-id":["10.1128\/AAC.39.2.462"],"URL":"https:\/\/doi.org\/10.1128\/aac.39.2.462","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,2]]},"assertion":[{"value":"1995-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}