{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T04:57:25Z","timestamp":1772600245647,"version":"3.50.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Graduate School of Biomedical Science, Nagasaki University"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            High-dose meropenem (MEPM; 6 g\/day) has been approved as a treatment for purulent meningitis; however, little is known regarding its\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy in refractory lower respiratory tract infections. The purpose of this study was to evaluate the efficacy of MEPM at 6 g\/day in a murine model of severe pneumonia caused by MEPM-resistant\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            . Experimental pneumonia induced by MEPM-resistant\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            was treated with normal-dose MEPM (150 mg\/kg of body weight, simulating a 3-g\/day regimen in humans) or high-dose MEPM (500 mg\/kg, simulating a 6-g\/day regimen in humans). Mice treated with high-dose MEPM showed significantly restored survival relative to that of untreated mice and tended to show a survival rate higher than that of mice treated with normal-dose MEPM. The viable bacterial counts (of two clinical isolates) in the lungs decreased significantly in mice treated with high-dose MEPM from those for untreated mice (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001) or mice treated with normal-dose MEPM (\n            <jats:italic>P<\/jats:italic>\n            , &lt;0.01 and &lt;0.05). The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was also significantly lower in mice treated with high-dose MEPM than in untreated mice. The free MEPM concentration in the epithelial lining fluid (ELF) exceeded 16 \u03bcg\/ml for 85 min in mice treated with high-dose MEPM, but not for mice treated with normal-dose MEPM. Our results demonstrate that high-dose MEPM (6 g\/day) might provide better protection against pneumonia caused by MEPM-resistant strains of\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            than the dose normally administered (less than 3 g\/day).\n          <\/jats:p>","DOI":"10.1128\/aac.02056-16","type":"journal-article","created":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T01:20:26Z","timestamp":1477963226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Efficacy of High-Dose Meropenem (Six Grams per Day) in Treatment of Experimental Murine Pneumonia Induced by Meropenem-Resistant Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"61","author":[{"given":"Kazuhiro","family":"Oshima","sequence":"first","affiliation":[{"name":"Leading Program, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"},{"name":"Unit of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"},{"name":"Department of Respiratory Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Iwanaga","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiga","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Unit of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"},{"name":"Department of Respiratory Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kastunori","family":"Yanagihara","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitsugu","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Mukae","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Kohno","sequence":"additional","affiliation":[{"name":"Department of Respiratory Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Izumikawa","sequence":"additional","affiliation":[{"name":"Unit of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit734"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-013-2828-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/377200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200405-644ST"},{"key":"e_1_3_2_6_2","first-page":"938","article-title":"Antibiotic resistance threats in the United States: stepping back from the brink","volume":"89","author":"Solomon SL","year":"2014","unstructured":"Solomon SL OliverKB. 2014. 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