{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:13:58Z","timestamp":1792678438687,"version":"4.5.0"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2010,10,1]],"date-time":"2010-10-01T00:00:00Z","timestamp":1285891200000},"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":["J Clin Microbiol"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Since carbapenemase-producing\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            strains were first reported in North Carolina, these highly resistant organisms have been isolated with increasing frequency, especially in the New York City area. Polymyxin B is one of the few antimicrobials that retain reliable activity against these organisms. However, polymyxin B MICs are elevated against\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            isolates with increasing frequency, leaving clinicians with few therapeutic options. We investigated several antimicrobial agents for potential synergy with polymyxin B against 12 clinical strains of carbapenemase-producing\n            <jats:italic>K. pneumoniae.<\/jats:italic>\n            A broth microdilution assay using a 96-well plate was developed in which graded dilutions of polymyxin B and the study drug were incubated with resistant isolates in a checkerboard pattern. Polymyxin B was studied in combination with cefazolin, ceftriaxone, cefepime, imipenem, gentamicin, tigecycline, doxycycline, and rifampin. All\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            strains tested positive for\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            carbapenemase (KPC) genes by real-time PCR and had elevated polymyxin B MIC values ranging from 16 to 128 \u03bcg\/ml. Synergy was observed with the combination of polymyxin B and rifampin as well as with polymyxin B and doxycycline, resulting in at least a 4-fold decrease in the polymyxin B MIC. For both combinations, this effect occurred at physiologically achievable concentrations. Less pronounced synergy was noted with tigecycline and polymyxin B. No synergy was observed at physiologic concentrations with the other antimicrobials studied. These results suggest that rifampin, doxycycline, and tigecycline may be useful additions to polymyxin B in the treatment of infections caused by highly resistant carbapenemase-producing\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            . Further studies are warranted to determine if these\n            <jats:italic>in vitro<\/jats:italic>\n            findings translate into clinical efficacy.\n          <\/jats:p>","DOI":"10.1128\/jcm.01106-10","type":"journal-article","created":{"date-parts":[[2010,8,5]],"date-time":"2010-08-05T03:56:49Z","timestamp":1280980609000},"page":"3558-3562","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":118,"title":["<i>In<\/i>\n            <i>Vitro<\/i>\n            Evaluation of Antibiotic Synergy for Polymyxin B-Resistant Carbapenemase-Producing\n            <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"48","author":[{"given":"Azza","family":"Elemam","sequence":"first","affiliation":[{"name":"Departments of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Rahimian","sequence":"additional","affiliation":[{"name":"Departments of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Doymaz","sequence":"additional","affiliation":[{"name":"Pathology\/Laboratories, Saint Vincent Medical Center, New York, New York 10011"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/512370"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki175"},{"key":"e_1_3_1_4_2","unstructured":"Performance standards for antimicrobial susceptibility testing. 2009"},{"key":"e_1_3_1_5_2","first-page":"271","volume":"49","year":"2007","unstructured":"Elemam, A., J. Rahimian, and W. Mandell. 2007. Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature. Clin. Infect. Dis. 49 : 271-274.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01169-07"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.5.5.811"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/MRM.0b013e3282f0b8b2"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00006-08"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02466-08"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp255"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/499404"},{"key":"e_1_3_1_13_2","first-page":"5.12.1","year":"2007","unstructured":"Moody, J. 2007. Synergism testing: broth microdilution checkerboard and broth macrodilution methods. Chapter 5.12, p. 5.12.1-5.12.23. In L. S. Garcia and H. D. Isenberg (ed.), Clinical microbiology procedures handbook, 2nd edition update. ASM Press, Washington, DC.","journal-title":"Clinical microbiology procedures handbook"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70054-4"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-007-0330-4"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm178"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm226"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-5-10"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.12.4793-4799.2004"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.753-757.2004"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.17.5.661"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm357"}],"container-title":["Journal of Clinical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JCM.01106-10","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JCM.01106-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T08:31:27Z","timestamp":1646469087000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JCM.01106-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10]]},"references-count":21,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2010,10]]}},"alternative-id":["10.1128\/JCM.01106-10"],"URL":"https:\/\/doi.org\/10.1128\/jcm.01106-10","relation":{},"ISSN":["0095-1137","1098-660X"],"issn-type":[{"value":"0095-1137","type":"print"},{"value":"1098-660X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10]]},"assertion":[{"value":"2010-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-07-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}