{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:30:30Z","timestamp":1789986630628,"version":"4.0.1"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Colistin has been revived, in the era of extensively drug-resistant (XDR) Gram-negative infections, as the last-resort treatment in critically ill patients. Recent studies focusing on the optimal dosing strategy of colistin have demonstrated the necessity of a loading dose at treatment initiation (D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, O. Cars, and H. Giamarellou, Antimicrob Agents Chemother 53:3430\u20133436, 2009,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1128\/AAC.01361-08\">http:\/\/dx.doi.org\/10.1128\/AAC.01361-08<\/jats:ext-link>\n            ; A. F. Mohamed, I. Karaiskos, D. Plachouras, M. Karvanen, K. Pontikis, B. Jansson, E. Papadomichelakis, A. Antoniadou, H. Giamarellou, A. Armaganidis, O. Cars, and L. E. Friberg, Antimicrob Agents Chemother 56:4241\u2013 4249, 2012,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1128\/AAC.06426-11\">http:\/\/dx.doi.org\/10.1128\/AAC.06426-11<\/jats:ext-link>\n            ; S. M. Garonzik, J. Li, V. Thamlikitkul, D. L. Paterson, S. Shoham, J. Jacob, F. P. Silveira, A. Forrest, and R. L. Nation, Antimicrob Agents Chemother 55:3284\u20133294, 2011,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1128\/AAC.01733-10\">http:\/\/dx.doi.org\/10.1128\/AAC.01733-10<\/jats:ext-link>\n            ). In 19 critically ill patients with suspected or microbiologically documented infections caused by XDR Gram-negative strains, a loading dose of 9 MU colistin methanesulfonate (CMS) (\u223c270 mg colistin base activity) was administered with a maintenance dose of 4.5 MU every 12 h, commenced after 24 h. Patients on renal replacement were excluded. CMS infusion was given over 30 min or 1 h. Repeated blood sampling was performed after the loading dose and after the 5th or 6th dose. Colistin concentrations and measured CMS, determined after hydrolization to colistin and including the partially sulfomethylated derivatives, were determined with a liquid chromatography-tandem mass spectrometry assay. Population pharmacokinetic analysis was conducted in NONMEM with the new data combined with data from previous studies. Measured colistimethate concentrations were described by 4 compartments for distribution and removal of sulfomethyl groups, while colistin disposition followed a 1-compartment model. The average observed maximum colistin A plus B concentration was 2.65 mg\/liter after the loading dose (maximum time was 8 h). A significantly higher availability of the measured A and B forms of colistimethate and colistin explained the higher-than-expected concentrations in the present study compared to those in previous studies. Creatinine clearance was a time-varying covariate of colistimethate clearance. The incidence of acute renal injury was 20%.\n          <\/jats:p>","DOI":"10.1128\/aac.00554-15","type":"journal-article","created":{"date-parts":[[2015,9,15]],"date-time":"2015-09-15T01:51:14Z","timestamp":1442281874000},"page":"7240-7248","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":104,"title":["Colistin Population Pharmacokinetics after Application of a Loading Dose of 9 MU Colistin Methanesulfonate in Critically Ill Patients"],"prefix":"10.1128","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2226-0239","authenticated-orcid":false,"given":"Ilias","family":"Karaiskos","sequence":"first","affiliation":[{"name":"6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena E.","family":"Friberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Pontikis","sequence":"additional","affiliation":[{"name":"1st Department of Respiratory Diseases\u2013Intensive Care Unit, Sotiria Hospital, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Ioannidis","sequence":"additional","affiliation":[{"name":"Clinical Pharmacist, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Tsagkari","sequence":"additional","affiliation":[{"name":"1st Department of Respiratory Diseases\u2013Intensive Care Unit, Sotiria Hospital, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamprini","family":"Galani","sequence":"additional","affiliation":[{"name":"6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Kostakou","sequence":"additional","affiliation":[{"name":"1st Department of Respiratory Diseases\u2013Intensive Care Unit, Sotiria Hospital, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotini","family":"Baziaka","sequence":"additional","affiliation":[{"name":"6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalambos","family":"Paskalis","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Koutsoukou","sequence":"additional","affiliation":[{"name":"1st Department of Respiratory Diseases\u2013Intensive Care Unit, Sotiria Hospital, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Giamarellou","sequence":"additional","affiliation":[{"name":"6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2014.914172"},{"key":"e_1_3_1_3_2","volume-title":"Antimicrobial resistance: no action today, no cure tomorrow","author":"World Health Organization (WHO)","year":"2011","unstructured":"World Health Organization (WHO). 2011. 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