{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:14:20Z","timestamp":1773800060562,"version":"3.50.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"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":[[2009,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            \u03b2-Lactamase-negative ampicillin-resistant (BLNAR) isolates of\n            <jats:italic>Haemophilus influenza<\/jats:italic>\n            <jats:italic>e<\/jats:italic>\n            have been emerging in some countries, including Japan. The Clinical and Laboratory Standards Institute has only a susceptible MIC breakpoint (\u22641 \u03bcg\/ml) for piperacillin-tazobactam and a disclaimer comment that BLNAR\n            <jats:italic>H. influenzae<\/jats:italic>\n            should be considered resistant, which was adapted without presentation of data. In addition, fluoroquinolone-resistant\n            <jats:italic>H. influenzae<\/jats:italic>\n            isolates have recently been occasionally reported worldwide. To address these problems, we examined susceptibilities to \u03b2-lactams, including piperacillin-tazobactam, and ciprofloxacin by microdilution and disk diffusion (only for piperacillin-tazobactam) methods, against a total of 400 recent\n            <jats:italic>H. influenzae<\/jats:italic>\n            clinical isolates, including 100 \u03b2-lactamase-negative ampicillin-susceptible, \u03b2-lactamase-positive ampicillin-resistant, BLNAR, and \u03b2-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) isolates each. BLNAR and BLPACR isolates were tested by PCR using primers that amplify specific regions of the\n            <jats:italic>ftsI<\/jats:italic>\n            gene. We also detected mutations in quinolone resistance-determining regions (QRDRs) by direct sequencing of the PCR products of DNA fragments. Among \u03b2-lactams, piperacillin-tazobactam exhibited potent activity against all isolates of\n            <jats:italic>H. influenzae<\/jats:italic>\n            , with all MICs at \u22640.5 \u03bcg\/ml (susceptible). A disk diffusion breakpoint for piperacillin-tazobactam of \u226521 mm is proposed. We confirmed that all BLNAR and BLPACR isolates had amino acid substitutions in the\n            <jats:italic>ftsI<\/jats:italic>\n            gene and that the major pattern was group III-like (87.5%). One ciprofloxacin-resistant isolate (MIC, 16 \u03bcg\/ml) and 31 ciprofloxacin-susceptible isolates (MICs, 0.06 to 0.5 \u03bcg\/ml) had amino acid changes in their QRDRs. Piperacillin-tazobactam was the most potent \u03b2-lactam tested against all classes of\n            <jats:italic>H. influenzae<\/jats:italic>\n            isolates. It is possible that fluoroquinolone-resistant\n            <jats:italic>H. influenzae<\/jats:italic>\n            will emerge since several clinical isolates carried mutations in their QRDRs.\n          <\/jats:p>","DOI":"10.1128\/aac.00192-09","type":"journal-article","created":{"date-parts":[[2009,8,4]],"date-time":"2009-08-04T01:41:09Z","timestamp":1249350069000},"page":"4225-4230","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Antimicrobial Activities of Piperacillin-Tazobactam against\n            <i>Haemophilus influenzae<\/i>\n            Isolates, Including \u03b2-Lactamase-Negative Ampicillin-Resistant and \u03b2-Lactamase-Positive Amoxicillin- Clavulanate-Resistant Isolates, and Mutations in Their Quinolone Resistance-Determining Regions"],"prefix":"10.1128","volume":"53","author":[{"given":"Yoichi","family":"Hirakata","sequence":"first","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"},{"name":"Department of Clinical Microbiology with Epidemiological Research &amp; Management and Analysis of Infectious Diseases (C-MERMAID)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Ohmori","sequence":"additional","affiliation":[{"name":"Mitsubishi Chemical Medience Corporation, Itabashi-ku, Tokyo 174-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miwako","family":"Mikuriya","sequence":"additional","affiliation":[{"name":"Mitsubishi Chemical Medience Corporation, Itabashi-ku, Tokyo 174-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Saika","sequence":"additional","affiliation":[{"name":"Mitsubishi Chemical Medience Corporation, Itabashi-ku, Tokyo 174-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Mitsubishi Chemical Medience Corporation, Itabashi-ku, Tokyo 174-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Mitsubishi Chemical Medience Corporation, Itabashi-ku, Tokyo 174-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masumitsu","family":"Hatta","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natsuo","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Kunishima","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisakazu","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"},{"name":"Department of Clinical Microbiology with Epidemiological Research &amp; Management and Analysis of Infectious Diseases (C-MERMAID)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuaki","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"},{"name":"Department of Clinical Microbiology with Epidemiological Research &amp; Management and Analysis of Infectious Diseases (C-MERMAID)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyoshi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Intetsu","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Prevention, Toho University School of Nursing, Ohtaku, Tokyo 143-0015, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald N.","family":"Jones","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa 52317"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Kohno","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Nagasaki University School of Medicine and Dentistry, Nagasaki 852-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keizo","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Ohtaku, Tokyo 143-8540, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuo","family":"Kaku","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Laboratory Diagnostics"},{"name":"Department of Clinical Microbiology with Epidemiological Research &amp; 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