{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:35:42Z","timestamp":1783528542481,"version":"3.55.0"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"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":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We previously demonstrated that the rate and extent of an antimicrobial agent's bactericidal effects were coupled to the bacterial replication rate, the latter of which was modulated with the sodium chloride concentration. Herein, we describe the results from a 24-h one-compartment\n            <jats:italic>in vitro<\/jats:italic>\n            infection model study that was designed to demonstrate that an antimicrobial agent's bactericidal effects could be amplified when it is administered with a pharmaceutical agent that increases the bacterial replication rate. The antimicrobial and growth-promoting agents selected were levofloxacin and norepinephrine, respectively. The challenge isolate was\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            JMI 21711R (levofloxacin MIC, 8 mg\/liter). Within the\n            <jats:italic>in vitro<\/jats:italic>\n            infection model, a human levofloxacin concentration-time profile (half-life, 7 h) was simulated and the challenge isolate was subjected to an ineffective monotherapy exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC\/MIC] ratio of 6) with and without norepinephrine as a continuous infusion (275 mg\/liter). Samples were collected from the model during the course of the study for bacterial density determinations and drug concentration assay using liquid chromatography-tandem mass spectrometry (LC-MS\/MS). As expected, the norepinephrine and no-treatment control arms failed immediately, followed by the levofloxacin monotherapy arm, which failed slowly over time. The levofloxacin-epinephrine regimen resulted in a 2-log\n            <jats:sub>10<\/jats:sub>\n            CFU reduction in bacterial density over the first 6 to 8 h of the study, which was followed by regrowth of a highly levofloxacin-resistant subpopulation (MIC, 64 mg\/liter). These data demonstrate that increasing the rate of bacterial replication with a pharmaceutical product in combination with antimicrobial therapy represents an opportunity to increase the rate and magnitude of bactericidal effect.\n          <\/jats:p>","DOI":"10.1128\/aac.02257-17","type":"journal-article","created":{"date-parts":[[2018,1,27]],"date-time":"2018-01-27T11:28:37Z","timestamp":1517052517000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Norepinephrine in Combination with Antibiotic Therapy Increases both the Bacterial Replication Rate and Bactericidal Activity"],"prefix":"10.1128","volume":"62","author":[{"given":"Paul G.","family":"Ambrose","sequence":"first","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"VanScoy","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Adams","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Fikes","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin C.","family":"Bader","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujata M.","family":"Bhavnani","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Schenectady, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01605-16"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1996.tb08196.x"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1999.tb13449.x"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb09463.x"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00075-06"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2614"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2333"},{"key":"e_1_3_1_9_2","first-page":"3","volume-title":"The activities of bacterial pathogens in vivo: based on contributions to a Royal Society discussion meeting","author":"Smith H","year":"2000","unstructured":"Smith H. 2000. The activities of bacterial pathogens in vivo: based on contributions to a Royal Society discussion meeting, p 3\u201338. In Smith H, Dorman CJ, Dougan G, Holden DW, Williams P (ed). Imperial College Press, London, United Kingdom."},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix211"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033447"},{"key":"e_1_3_1_12_2","volume-title":"Northera (droxidopa) capsules prescribing information","author":"Lundbeck NA Ltd","year":"2014","unstructured":"Lundbeck NA Ltd. 2014. Northera (droxidopa) capsules prescribing information. Lundbeck NA Ltd, Deerfield, IL."},{"key":"e_1_3_1_13_2","volume-title":"Sinemet (carbidopa-levodopa) tablets prescribing information","author":"Bristol-Myers Squibb","year":"2009","unstructured":"Bristol-Myers Squibb. 2009. Sinemet (carbidopa-levodopa) tablets prescribing information. Bristol-Myers Squibb, Princeton, NJ."},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-5576-0"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01802-13"},{"key":"e_1_3_1_17_2","volume-title":"CLSI document M07-A9","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 9th ed. CLSI document M07-A9. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"9"},{"key":"e_1_3_1_18_2","unstructured":"United States Committee on Antimicrobial Susceptibility Testing. 2017. Quinolone in vitro susceptibility test interpretive criteria evaluations (V1.2). United States Committee on Antimicrobial Susceptibility Testing. https:\/\/app.box.com\/s\/hxo1zbtunse7zse19ibxwza7u190rmla."},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00656-13"},{"key":"e_1_3_1_20_2","volume-title":"Levaquin (levofloxacin)\u00ae package insert","author":"Janssen Pharmaceuticals","year":"2014","unstructured":"Janssen Pharmaceuticals. 2014. Levaquin (levofloxacin)\u00ae package insert. Janssen Pharmaceuticals, Raritan, NJ."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02257-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02257-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:07:04Z","timestamp":1645477624000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02257-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1128\/AAC.02257-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.02257-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"2017-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02257-17"}}