{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:30:07Z","timestamp":1787016607317,"version":"build-2736575974"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2007,7,1]],"date-time":"2007-07-01T00:00:00Z","timestamp":1183248000000},"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":[[2007,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The sequence of the\n                    <jats:italic>ftsI<\/jats:italic>\n                    gene encoding the transpeptidase domain of penicillin-binding protein 3 (PBP 3) was determined for 354 nonconsecutive\n                    <jats:italic>Haemophilus influenzae<\/jats:italic>\n                    isolates from Spain; 17.8% of them were ampicillin susceptible, 56% were \u03b2-lactamase nonproducing ampicillin resistant (BLNAR), 15.8% were \u03b2-lactamase producers and ampicillin resistant, and 10.4% displayed both resistance mechanisms. The\n                    <jats:italic>ftsI<\/jats:italic>\n                    gene sequences had 28 different mutation patterns and amino acid substitutions at 23 positions. Some 93.2% of the BLNAR strains had amino acid substitutions at the Lys-Thr-Gly (KTG) motif, the two most common being Asn526 to Lys (83.9%) and Arg517 to His (9.3%). Amino acid substitutions at positions 377, 385, and 389, which conferred cefotaxime and cefixime MICs 10 to 60 times higher than those of susceptible strains, were found for the first time in Europe. In 72 isolates for which the repressor\n                    <jats:italic>acrR<\/jats:italic>\n                    gene of the AcrAB efflux pump was sequenced, numerous amino acid substitutions were found. Eight isolates with ampicillin MICs of 0.25 to 2 \u03bcg\/ml showed changes that predicted the early termination of the\n                    <jats:italic>acrR<\/jats:italic>\n                    reading frame. Pulsed-field gel electrophoresis analysis demonstrated that most BLNAR strains were genetically diverse, although clonal dissemination was detected in a group of isolates presenting with increased resistance to cefotaxime and cefixime. Background antibiotic use at the community level revealed a marked trend toward increased amoxicillin-clavulanic acid consumption. BLNAR\n                    <jats:italic>H. influenzae<\/jats:italic>\n                    strains have arisen by vertical and horizontal spread and have evolved to adapt rapidly to the increased selective pressures posed by the use of oral penicillins and cephalosporins.\n                  <\/jats:p>","DOI":"10.1128\/aac.00354-07","type":"journal-article","created":{"date-parts":[[2007,4,30]],"date-time":"2007-04-30T21:05:03Z","timestamp":1177967103000},"page":"2564-2573","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":124,"title":["Ampicillin-Resistant Non-\u03b2-Lactamase-Producing\n                    <i>Haemophilus influenzae<\/i>\n                    in Spain: Recent Emergence of Clonal Isolates with Increased Resistance to Cefotaxime and Cefixime"],"prefix":"10.1128","volume":"51","author":[{"given":"Silvia","family":"Garci\u0301a-Cobos","sequence":"first","affiliation":[{"name":"Antibiotic Laboratory, Bacteriology Centro Nacional de Microbiologi\u0301a, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301","family":"Campos","sequence":"additional","affiliation":[{"name":"Antibiotic Laboratory, Bacteriology Centro Nacional de Microbiologi\u0301a, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"},{"name":"Consejo Superior de Investigaciones Cienti\u0301ficas, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edurne","family":"La\u0301zaro","sequence":"additional","affiliation":[{"name":"Divisio\u0301n de Farmacovigilancia, Agencia Espan\u0303ola del Medicamento, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Roma\u0301n","sequence":"additional","affiliation":[{"name":"Antibiotic Laboratory, Bacteriology Centro Nacional de Microbiologi\u0301a, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Cercenado","sequence":"additional","affiliation":[{"name":"Microbiology Department, Hospital Gregorio Maran\u0303o\u0301n, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce\u0301sar","family":"Garci\u0301a-Rey","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline S.A., Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u0301a","family":"Pe\u0301rez-Va\u0301zquez","sequence":"additional","affiliation":[{"name":"Antibiotic Laboratory, Bacteriology Centro Nacional de Microbiologi\u0301a, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesu\u0301s","family":"Oteo","sequence":"additional","affiliation":[{"name":"Antibiotic Laboratory, Bacteriology Centro Nacional de Microbiologi\u0301a, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"de Abajo","sequence":"additional","affiliation":[{"name":"Divisio\u0301n de Farmacovigilancia, Agencia Espan\u0303ola del Medicamento, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.44.5.1645-1649.2006"},{"key":"e_1_3_2_3_2","first-page":"279","year":"1980","unstructured":"Bell, S. 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