016f49c8711abd84ed455acd42b31a56 pmc_30717123.pdf a9dadbe6911776d82cfe5733d7de48c8f5dbdc99 pmc_30717123.pdf 2f6e4e3649d9c2b0aabae1e5c5f04a349d536458e810d962ca9234f4e0df608c pmc_30717123.pdf Title: Colistin Use in Patients with Chronic Kidney Disease: Are We Underdosing Patients? Subject: Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m2 for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45–95) years and baseline GFR was 36.6 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2–2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments. Keywords: colistin; colistin plasma concentrations; chronic kidney disease; pharmacokinetic; toxicodynamic Author: Luisa Sorli, Sonia Luque, Jian Li, Eva Rodríguez, Nuria Campillo, Xenia Fernandez, Jade Soldado, Ignacio Domingo, Milagro Montero, Santiago Grau and Juan P. 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MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 106 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 158 0 ACJDEO+Symbol Type 1C Custom yes yes yes 163 0 ACJCIO+PalatinoLinotype TrueType WinAnsi yes yes no 164 0 ACJCLO+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 165 0 ACJCMA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 166 0 ACJDHO+TimesNewRoman CID TrueType Identity-H yes yes yes 167 0 JLZORU+EURM10 Type 1 Builtin yes yes no 318 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2020-11-19 06:17:42 CET RepresentationInformation: pmc_30717123.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-08-03 03:45:06 CEST Size: 407932 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰こぴふつべぜ〴ぜ〰ぐはばふぬちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぃはぬぬづっぴづつぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぃきこぜ〴ぜ〰ぁつねどのどびぴひちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰きどっひはぢどはぬはでどっちぬぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Children: Item: Title: こぴふつべぜ〴ぜ〰ぐはばふぬちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぃはぬぬづっぴづつぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぃきこぜ〴ぜ〰ぁつねどのどびぴひちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰きどっひはぢどはぬはでどっちぬぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: ぃはぬぬづっぴづつぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㌩‾㸊⡜㌷㙜㌷㝜〰いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぃきこぜ〴ぜ〰ぁつねどのどびぴひちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰きどっひはぢどはぬはでどっちぬぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: いづてどのどぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㐩‾㸊⡜㌷㙜㌷㝜〰ぃきこぜ〴ぜ〰ぁつねどのどびぴひちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰きどっひはぢどはぬはでどっちぬぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: ぃきこぜ〴ぜ〰ぁつねどのどびぴひちぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㔩‾㸊⡜㌷㙜㌷㝜〰きどっひはぢどはぬはでどっちぬぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: きどっひはぢどはぬはでどっちぬぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㘩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: ぐとちひねちっはにどのづぴどっぜ〴ぜ〰いちぴちぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: こぴちぴどびぴどっちぬぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㜩‾㸊⡜㌷㙜㌷㝜〰げづてづひづのっづび Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: QOETIB+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: QOETIB+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: BDFJZJ+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: 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