{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T18:35:56Z","timestamp":1775154956918,"version":"3.50.1"},"reference-count":30,"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":["R56 AI111985"],"award-info":[{"award-number":["R56 AI111985"]}],"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 continue to be part of the backbone of treatment of multidrug-resistant tuberculosis (MDR-TB). We measured amikacin concentrations in 28 MDR-TB patients in Botswana receiving amikacin therapy together with oral levofloxacin, ethionamide, cycloserine, and pyrazinamide and calculated areas under the concentration-time curves from 0 to 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ). The patients were followed monthly for sputum culture conversion based on liquid cultures. The median duration of amikacin therapy was 184 (range, 28 to 866) days, at a median dose of 17.30 (range 11.11 to 19.23) mg\/kg. Only 11 (39%) patients had sputum culture conversion during treatment; the rest failed. We utilized classification and regression tree analyses (CART) to examine all potential predictors of failure, including clinical and demographic features, comorbidities, and amikacin peak concentrations (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ), AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            , and trough concentrations. The primary node for failure had two competing variables,\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            of &lt;67 mg\/liter and AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            of &lt;568.30 mg \u00b7 h\/L; weight of &gt;41 kg was a secondary node with a score of 35% relative to the primary node. The area under the receiver operating characteristic curve for the CART model was an R\n            <jats:sup>2<\/jats:sup>\n            = 0.90 on posttest. In patients weighing &gt;41 kg, sputum conversion was 3\/3 (100%) in those with an amikacin\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            of \u226567 mg\/liter versus 3\/15 (20%) in those with a\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            of &lt;67 mg\/liter (relative risk [RR] = 5.00; 95% confidence interval [CI], 1.82 to 13.76). In all patients who had both amikacin\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            and AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            below the threshold, 7\/7 (100%) failed, compared to 7\/15 (47%) of those who had these parameters above threshold (RR = 2.14; 95% CI, 1.25 to 43.68). These amikacin dose-schedule patterns and exposures are virtually the same as those identified in the hollow-fiber system model.\n          <\/jats:p>","DOI":"10.1128\/aac.00962-16","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T02:33:19Z","timestamp":1469500399000},"page":"5928-5932","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Artificial Intelligence and Amikacin Exposures Predictive of Outcomes in Multidrug-Resistant Tuberculosis Patients"],"prefix":"10.1128","volume":"60","author":[{"given":"Chawangwa","family":"Modongo","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Botswana-University of Pennsylvania Partnership, Gaborone, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jotam G.","family":"Pasipanodya","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research &amp; Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beki T.","family":"Magazi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University of Pretoria, Pretoria, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shashikant","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research &amp; Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola M.","family":"Zetola","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania, USA"},{"name":"Botswana-University of Pennsylvania Partnership, Gaborone, Botswana"},{"name":"Department of Medicine, University of Botswana, Gaborone, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Sirugo","sequence":"additional","affiliation":[{"name":"Centro di Ricerca, Ospedale San Pietro Fatebenefratelli, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tawanda","family":"Gumbo","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases Research &amp; 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":[{"role":"author","vocabulary":"crossref"}]}],"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":"10.1183\/09031936.00073611"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001300"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01050-15"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00961-16"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ426"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ427"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ425"},{"key":"e_1_3_2_10_2","first-page":"218","article-title":"Nonlinear science: from paradigms to practicalities","volume":"1987","author":"Campbell DK","year":"1987","unstructured":"Campbell DK. 1987. Nonlinear science: from paradigms to practicalities. Los Alamos Sci Spec Issue 1987:218\u2013262.","journal-title":"Los Alamos Sci Spec Issue"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03931-14"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit352"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1145\/3341.3345"},{"key":"e_1_3_2_14_2","volume-title":"Classification and regression trees","author":"Breiman L","year":"1984","unstructured":"Breiman L, Friedman J, Stone CJ, Olshen RA. 1984. Classification and regression trees. Chapman and Hall\/CRC, Boca Raton, FL."},{"key":"e_1_3_2_15_2","volume-title":"Annu Meet Soc Acad Emergency Med","author":"Lewis RJ","year":"2000","unstructured":"Lewis RJ. 2000. An introduction to classification and regression tree (CART) analysis. 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