{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:34:19Z","timestamp":1762864459395},"reference-count":45,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2000,6,1]],"date-time":"2000-06-01T00:00:00Z","timestamp":959817600000},"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":[[2000,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Twenty-two\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            and two\n            <jats:italic>K. oxytoca<\/jats:italic>\n            extended-spectrum \u03b2-lactamase (ESBL)-producing isolates were collected in 1996 from patients in two pediatric wards of the University Hospital in Wroc\u0142aw, Poland. Molecular typing has revealed that the\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            isolates represented four different epidemic strains. Three kinds of enzymes with ESBL activity (pI values of 5.7, 6.0, and 8.2) were identified. The pI 6.0 \u03b2-lactamases belonged to the TEM family, and sequencing of the\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>TEM<\/jats:sub>\n            genes amplified from representative isolates revealed that these enzymes were TEM-47, previously identified in\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            isolates from pediatric hospitals in \u0141o\u0301dz\u0301 and Warsaw. One of the TEM-47-producing strains from Wroc\u0142aw was very closely related to the isolates from the other cities, and this indicated countrywide spread of the epidemic strain. The pI 5.7 \u03b2-lactamase was produced by a single\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            isolate for which, apart from oxyimino-\u03b2-lactams, the MICs of \u03b2-lactam\u2013inhibitor combinations were also remarkably high. Sequencing revealed that this was a novel TEM \u03b2-lactamase variant, TEM-68, specified by the following combination of mutations: Gly238Ser, Glu240Lys, Thr265Met, and Arg275Leu. The new enzyme has most probably evolved from TEM-47 by acquiring the single substitution of Arg275, which before was identified only twice in enzymes with inhibitor resistance (IR) activity. TEM-68 was shown to be a novel complex mutant TEM \u03b2-lactamase (CMT-2) which combines strong ESBL activity with relatively weak IR activity and, when expressed in\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            , is able to confer high-level resistance to a wide variety of \u03b2-lactams, including inhibitor combinations. This data confirms the role of the Arg275Leu mutation in determining IR activity and documents the first isolation of\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            producing the complex mutant enzyme.\n          <\/jats:p>","DOI":"10.1128\/aac.44.6.1499-1505.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"1499-1505","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["A Novel Complex Mutant \u03b2-Lactamase, TEM-68, Identified in a\n            <i>Klebsiella pneumoniae<\/i>\n            Isolate from an Outbreak of Extended-Spectrum \u03b2-Lactamase-Producing Klebsiellae"],"prefix":"10.1128","volume":"44","author":[{"given":"Janusz","family":"Fiett","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Sera &amp; Vaccines Central Research Laboratory, 00-725 Warsaw,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Pa\u0142ucha","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Biochemistry and Biophysics, 02-106 Warsaw,2 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Mia\u02dbczyn\u0301ska","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Microbiology, Wroc\u0142aw Medical University, 50-368 Wroc\u0142aw,3 Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Stankiewicz","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Microbiology, Wroc\u0142aw Medical University, 50-368 Wroc\u0142aw,3 Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Przondo-Mordarska","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Department of Microbiology, Wroc\u0142aw Medical University, 50-368 Wroc\u0142aw,3 Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waleria","family":"Hryniewicz","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Sera &amp; Vaccines Central Research Laboratory, 00-725 Warsaw,1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Gniadkowski","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Sera &amp; Vaccines Central Research Laboratory, 00-725 Warsaw,1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2760269"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/jac\/42.4.415","article-title":"Extended-spectrum \u03b2-lactamases: the role of inhibitors in therapy.","volume":"42","author":"Amyes S. G. B.","year":"1998","unstructured":"Amyes S. G. B. Miles R. S. Extended-spectrum \u03b2-lactamases: the role of inhibitors in therapy. J. Antimicrob. Chemother. 42 1998 415 417","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01704610"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.3.616"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.12.2439"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/7.6.1513"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.4.761"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.4.899"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/38.2.183"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.851"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.2.374"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.2.913-916.1987"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(84)90207-5"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.12.3079"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.3.514"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.32.2.301-305.1994"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0378-1119(91)90540-R","article-title":"Sequences of the genes bla-T1b and bla-T2.","volume":"102","author":"Goussard S.","year":"1991","unstructured":"Goussard S. Courvalin P. Sequences of the genes bla-T1b and bla-T2. Gene 102 1991 71 73","journal-title":"Gene"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.2.427"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/10.4.867"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.32.1.9"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.12.2593"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0195-6701(95)90064-0"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.11.2580"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.8.4.557"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0147-619X(90)90041-A"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-88-1-169"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1093\/clinids\/24.Supplement_1.S19","article-title":"Evolution and dissemination of \u03b2-lactamases accelerated by generations of \u03b2-lactam antibiotics.","volume":"24","author":"Medeiros A. A.","year":"1997","unstructured":"Medeiros A. A. Evolution and dissemination of \u03b2-lactamases accelerated by generations of \u03b2-lactam antibiotics. Clin. Infect. Dis. 24 (Suppl. 1) 1997 S19 S45","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_29_2","unstructured":"National Committee for Clinical Laboratory Standards\n          Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A4. Performance standards for antimicrobial susceptibility testing; ninth informational supplement January 1999.\n          1997\n          National Committee for Clinical Laboratory Standards\n          Wayne Pa"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/40.1.1"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.2.393"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/44.4.489"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.1.108"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.838"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.3.647"},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S1198-743X(15)60285-3","article-title":"Typing of Pseudomonas aeruginosa strains from patients with cystic fibrosis: phenotyping versus genotyping.","volume":"1","author":"Renders N.","year":"1996","unstructured":"Renders N. van Belkum A. Barth A. Goessens W. Mouton J. Verbrugh H. Typing of Pseudomonas aeruginosa strains from patients with cystic fibrosis: phenotyping versus genotyping. Clin. Microbiol. Infect. 1 1996 261 265","journal-title":"Clin. Microbiol. Infect."},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/23.1.118"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.12.5463"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/25.3.343"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2184"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1322"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(93)90331-I"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.8.3737"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.33.9.2233-2239.1995"},{"key":"e_1_3_2_45_2","first-page":"113","article-title":"TRC-1: emergence of clavulanic acid-resistant TEM \u03b2-lactamase in a clinical strain.","volume":"91","author":"Thomson C. J.","year":"1992","unstructured":"Thomson C. J. Amyes S. G. B. TRC-1: emergence of clavulanic acid-resistant TEM \u03b2-lactamase in a clinical strain. FEMS Microbiol. Lett. 91 1992 113 118","journal-title":"FEMS Microbiol. Lett."},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/jac\/30.4.449","article-title":"Clinical isolates of Escherichia coli producing TRI \u03b2-lactamases: novel TEM-enzymes conferring resistance to \u03b2-lactamase inhibitors.","volume":"30","author":"Vedel G.","year":"1992","unstructured":"Vedel G. Belaaouaj A. Gilly L. Labia R. Philippon A. Nevot P. Paul G. Clinical isolates of Escherichia coli producing TRI \u03b2-lactamases: novel TEM-enzymes conferring resistance to \u03b2-lactamase inhibitors. J. Antimicrob. Chemother. 30 1992 449 462","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.6.1499-1505.2000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.44.6.1499-1505.2000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:54:04Z","timestamp":1645462444000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.44.6.1499-1505.2000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,6]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2000,6]]}},"alternative-id":["10.1128\/AAC.44.6.1499-1505.2000"],"URL":"https:\/\/doi.org\/10.1128\/aac.44.6.1499-1505.2000","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,6]]},"assertion":[{"value":"1999-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}