{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:11:08Z","timestamp":1791234668186,"version":"4.1.0"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2005,7,1]],"date-time":"2005-07-01T00:00:00Z","timestamp":1120176000000},"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":[[2005,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Chemotherapy of tuberculosis caused by multiple-drug-resistant (MDR) strains is problematic because of choices limited to relatively inefficacious and toxic drugs. Some beta-lactam antibiotics are active against\n            <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n            in vitro. We investigated the efficacy of imipenem in a mouse model of tuberculosis and in humans with MDR tuberculosis. Mice infected with\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            strain H37Rv were treated with isoniazid or imipenem. Residual organisms in lung and spleen and survival of imipenem-treated mice were compared to those of untreated or isoniazid-treated mice. Ten patients with MDR tuberculosis also were treated with imipenem in combination with other first- or second-line agents; elimination of\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            from sputum samples was measured by quantitative culture. Although it was less effective than isoniazid, imipenem significantly reduced the numbers of\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            organisms in lungs and spleens and improved survival of mice. Eight of 10 patients with numerous risk factors for poor outcomes responded to imipenem combination therapy with conversion of cultures to negative. Seven remained culture-negative off of therapy. There were two deaths, one of which was due to active tuberculosis. Organisms were eliminated from the sputa of responders at a rate of 0.35 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml\/week. Relapse upon withdrawal of imipenem and development of resistance to imipenem in a nonresponder suggest that imipenem exerts antimycobacterial activity in humans infected with\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            . Imipenem had antimycobacterial activity both in a mouse model and in humans at high risk for failure of treatment for MDR tuberculosis.\n          <\/jats:p>","DOI":"10.1128\/aac.49.7.2816-2821.2005","type":"journal-article","created":{"date-parts":[[2005,6,25]],"date-time":"2005-06-25T02:22:50Z","timestamp":1119666170000},"page":"2816-2821","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["Imipenem for Treatment of Tuberculosis in Mice and Humans"],"prefix":"10.1128","volume":"49","author":[{"given":"Henry F.","family":"Chambers","sequence":"first","affiliation":[{"name":"Medical Service, San Francisco General Hospital, Department of Medicine, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Turner","sequence":"additional","affiliation":[{"name":"Medical Service, San Francisco General Hospital, Department of Medicine, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela F.","family":"Schecter","sequence":"additional","affiliation":[{"name":"Medical Service, San Francisco General Hospital, Department of Medicine, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masae","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Medical Service, San Francisco General Hospital, Department of Medicine, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Hopewell","sequence":"additional","affiliation":[{"name":"Medical Service, San Francisco General Hospital, Department of Medicine, University of California San Francisco, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/513945"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.12.2620"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.24.3.429"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/jac\/18.1.6","volume":"18","year":"1986","unstructured":"Finch, R. 1986. Beta-lactam antibiotics and mycobacteria. J. Antimicrob. Chemother.18:6-8.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199302253280802"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1182"},{"key":"e_1_3_2_8_2","first-page":"84","volume":"9","year":"1994","unstructured":"Heifets, L. B. 1994. Antimycobacterial drugs. Semin. Respir. Infect.9:84-103.","journal-title":"Semin. Respir. Infect."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1164\/arrd.1965.91.1.117","volume":"91","year":"1965","unstructured":"Kasik, J. 1965. The nature of mycobacterial penicillinase. Am. Rev. Respir. Dis.91:117-119.","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.7.1476"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.4582.769"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1378\/chest.99.4.1025","volume":"99","year":"1991","unstructured":"Nadler, J. P., J. Berger, J. A. Nord, R. Cofsky, and M. Saxena. 1991. Amoxicillin-clavulanic acid for treating drug-resistant Mycobacterium tuberculosis. Chest99:1025-1026.","journal-title":"Chest"},{"key":"e_1_3_2_13_2","first-page":"1273","year":"2001","unstructured":"Petri, W. A. 2001. Drugs used in the chemotherapy of tuberculosis, Mycobacterium avium complex disease, and leprosy, p. 1273-1294. In J. G. Hardman and L. E. Limbard (ed.), The pharmacological basis of therapeutics, 10th ed. McGraw-Hill, New York, N.Y.","journal-title":"The pharmacological basis of therapeutics"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107193450303"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199510053331404"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0962-8479(92)90145-A","volume":"73","year":"1992","unstructured":"Watt, B., J. R. Edwards, A. Rayner, A. J. Grindey, and G. Harris. 1992. In vitro activity of meropenem and imipenem against mycobacteria: development of a daily antibiotic dosing schedule. Tuber. Lung Dis.73:134-136.","journal-title":"Tuber. Lung Dis."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.7.1944-1947.1995"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.117.3.744"},{"key":"e_1_3_2_19_2","first-page":"394","volume":"51","year":"1996","unstructured":"Yew, W. W., and C. H. Chau. 1996. New antimycobacterial agents. Monaldi Arch. Chest Dis.51:394-404.","journal-title":"Monaldi Arch. Chest Dis."},{"key":"e_1_3_2_20_2","first-page":"90","volume":"76","year":"1995","unstructured":"Yew, W. W., C. F. Wong, J. Lee, P. C. Wong, and C. H. Chau. 1995. Do beta-lactam-beta-lactamase inhibitor combinations have a place in the treatment of multidrug-resistant pulmonary tuberculosis? Tuber. Lung Dis.76:90-92.","journal-title":"Tuber. Lung Dis."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.49.7.2816-2821.2005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.49.7.2816-2821.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T19:09:44Z","timestamp":1645470584000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.49.7.2816-2821.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2005,7]]}},"alternative-id":["10.1128\/AAC.49.7.2816-2821.2005"],"URL":"https:\/\/doi.org\/10.1128\/aac.49.7.2816-2821.2005","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7]]},"assertion":[{"value":"2004-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}