{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:01:12Z","timestamp":1790805672949,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R56AI111985"],"award-info":[{"award-number":["R56AI111985"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Aminoglycosides such as amikacin are currently used for the treatment of multidrug-resistant tuberculosis (MDR-TB). However, formal pharmacokinetic\/pharmacodynamic (PK\/PD) studies to identify amikacin exposures and dosing schedules that optimize\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            killing have not been performed. It is believed that aminoglycosides do not work well under acidic conditions, which, if true, would mean poor sterilizing activity against semidormant bacilli at low pH. We performed time-kill studies to compare the bactericidal effect of amikacin in log-phase-growth bacilli with the sterilizing effect in semidormant bacilli at pH 5.8 in broth. In log-phase\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            at normal pH versus semidormant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            at pH 5.8, the maximal kill (\n            <jats:italic>E<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ) estimate and 95% confidence interval (CI) were 5.39 (95% CI, 4.91 to 5.63) versus 4.88 (CI, 4.46 to 5.22) log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml, while the concentration mediating 50% of\n            <jats:italic>E<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            (EC\n            <jats:sub>50<\/jats:sub>\n            ) was 1.0 (CI, 0. 0.86 to 1.12) versus 0.60 (CI, 0.50 to 0.66) times the MIC, respectively. Thus, the optimal exposures and kill rates identified for log-phase\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            will be optimal even for semidormant bacilli. Next, we performed exposure-response and dose-scheduling studies in the hollow-fiber system model of tuberculosis using log-phase\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            . We recapitulated the amikacin concentration-time profiles observed in lungs of patients treated over 28 days. The PK\/PD index linked to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            kill was the peak concentration (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            )-to-MIC ratio (\n            <jats:italic>r<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            &gt; 0.99), closely followed by the area under the concentration-time curve from 0 to 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            )-to-MIC ratio (\n            <jats:italic>r<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            = 0.98). The EC\n            <jats:sub>90<\/jats:sub>\n            was a\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            \/MIC ratio of 10.13 (95% CI, 7.73 to 12.48). The EC\n            <jats:sub>90<\/jats:sub>\n            is the dosing target for intermittent therapy that optimizes cure in TB programs for MDR-TB patients.\n          <\/jats:p>","DOI":"10.1128\/aac.00961-16","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T02:33:19Z","timestamp":1469500399000},"page":"5922-5927","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Amikacin Optimal Exposure Targets in the Hollow-Fiber System Model of Tuberculosis"],"prefix":"10.1128","volume":"60","author":[{"given":"Shashikant","family":"Srivastava","sequence":"first","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chawanga","family":"Modongo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Botswana-University of Pennsylvania Partnership, Gaborone, Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandima W.","family":"Siyambalapitiyage Dona","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jotam G.","family":"Pasipanodya","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devyani","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawanda","family":"Gumbo","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA"},{"name":"Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70031-1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808427"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112433"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1201964"},{"key":"e_1_3_2_6_2","volume-title":"WHO\/HTM\/TB\/2009.420","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 2010. Treatment of tuberculosis: guidelines, 4th ed. WHO\/HTM\/TB\/2009.420. 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