{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:16:38Z","timestamp":1762161398591},"reference-count":29,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[1999,5,1]],"date-time":"1999-05-01T00:00:00Z","timestamp":925516800000},"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":[[1999,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            An important mechanism of bacterial resistance to \u03b2-lactam antibiotics is inactivation by \u03b2-lactam-hydrolyzing enzymes (\u03b2-lactamases). The evolution of the extended-spectrum \u03b2-lactamases (ESBLs) is associated with extensive use of \u03b2-lactam antibiotics, particularly cephalosporins, and is a serious threat to therapeutic efficacy. ESBLs and broad-spectrum \u03b2-lactamases (BDSBLs) are plasmid-mediated class A enzymes produced by gram-negative pathogens, principally\n            <jats:italic>Escherichia coli<\/jats:italic>\n            and\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            . MK-0826 was highly potent against all ESBL- and BDSBL-producing\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            and\n            <jats:italic>E. coli<\/jats:italic>\n            clinical isolates tested (MIC range, 0.008 to 0.12 \u03bcg\/ml). In\n            <jats:italic>E. coli<\/jats:italic>\n            , this activity was associated with high-affinity binding to penicillin-binding proteins 2 and 3. When the inoculum level was increased 10-fold, increasing the amount of \u03b2-lactamase present, the MK-0826 MIC range increased to 0.008 to 1 \u03bcg\/ml. By comparison, similar observations were made with meropenem while imipenem MICs were usually less affected. Not surprisingly, MIC increases with noncarbapenem \u03b2-lactams were generally substantially greater, resulting in resistance in many cases.\n            <jats:italic>E. coli<\/jats:italic>\n            strains that produce chromosomal (Bush group 1) \u03b2-lactamase served as controls. All three carbapenems were subject to an inoculum effect with the majority of the BDSBL- and ESBL-producers but not the Bush group 1 strains, implying some effect of the plasmid-borne enzymes on potency. Importantly, MK-0826 MICs remained at or below 1 \u03bcg\/ml under all test conditions.\n          <\/jats:p>","DOI":"10.1128\/aac.43.5.1170","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:34:57Z","timestamp":1539045297000},"page":"1170-1176","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":60,"title":["In Vitro Activities of the Potent, Broad-Spectrum Carbapenem MK-0826 (L-749,345) against Broad-Spectrum \u03b2-Lactamase-and Extended-Spectrum \u03b2-Lactamase-Producing\n            <i>Klebsiella pneumoniae<\/i>\n            and\n            <i>Escherichia coli<\/i>\n            Clinical Isolates"],"prefix":"10.1128","volume":"43","author":[{"given":"Joyce","family":"Kohler","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Departments of Infectious Diseases1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Dorso","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Infectious Diseases1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Young","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Infectious Diseases1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail G.","family":"Hammond","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Biochemistry,2 Merck Research Laboratories, Rahway, New Jersey 07065-0900"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"Rosen","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Infectious Diseases1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helmut","family":"Kropp","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Infectious Diseases1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn L.","family":"Silver","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Infectious Diseases1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Barry\n              A. L.\n              Fuchs\n              P. C.\n              Brown\n              S. D.\n          In vitro activity of the carbapenem MK-0826 (L-749 345) and provisional criteria for disk tests abstr. D-38\n          Abstracts of the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1998\n          138\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.3.259"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1211"},{"key":"e_1_3_2_5_2","unstructured":"Dorso\n              K.\n              Kohler\n              J.\n              Silver\n              L. L.\n              Kropp\n              H.\n          Bactericidal effect of L-749 345 on Staphylococcus aureus and Serratia marcescens in the presence and absence of human serum abstr. F-123\n          Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1996\n          121\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.28.5.601"},{"key":"e_1_3_2_7_2","unstructured":"Gerckens\n              L. S.\n              Pelak\n              B. A.\n              Thompson\n              R.\n              Rosen\n              H.\n              Kropp\n              H.\n          Pharmacokinetic evaluation of L-749 345 (ZD-4433) a long-acting parenteral carbapenem in rodents abstr. F127\n          Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1996\n          122\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.8.1996"},{"key":"e_1_3_2_9_2","unstructured":"Gill\n              C. J.\n              Jackson\n              J. J.\n              Sundelof\n              J. G.\n              Rosen\n              H.\n              Kropp\n              H. In vivo activity of a novel long-acting carbapenem antibiotic L-749 345 in mouse models of localized and systemic bacterial infections abstr. F125\n          Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1996\n          121\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.3.560"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.8.1830"},{"key":"e_1_3_2_12_2","unstructured":"Kohler\n              J.\n              Dorso\n              K.\n              Pelak\n              B. A.\n              Gerckens\n              L. S.\n              Hammond\n              G. G.\n              Silver\n              L. L.\n              Kropp\n              H. In vitro activity of the potent broad-spectrum carbapenem L-749 345 against BDS\u03b2L- and ES\u03b2L-producing Escherichia coli and Klebsiella pneumoniae clinical isolates abstr. F122\n          Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy.\n          1996\n          121\n          American Society for Microbiology\n          Washington D.C"},{"key":"e_1_3_2_13_2","unstructured":"Kohler\n              J.\n              Dorso\n              K.\n              Young\n              K.\n              Hirsch\n              C.\n              Silver\n              L. L.\n              Kropp\n              H.\n          Evaluation of resistance selection potential of the new carbapenem L-749 345 in \u03b2-lactamase-producing Escherichia coli clinical isolates abstr. 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Personal communication."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/35.1.75"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.12.3609-3614.1991"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.5.1170","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.5.1170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:24:53Z","timestamp":1645460693000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.43.5.1170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,5]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1999,5]]}},"alternative-id":["10.1128\/AAC.43.5.1170"],"URL":"https:\/\/doi.org\/10.1128\/aac.43.5.1170","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,5]]},"assertion":[{"value":"1998-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}