29df4fc2cd59413cc2270bf3411564d5 pmc_33321721.pdf 9627651dc9c5e398384fb6810ec6ab80cd6428b6 pmc_33321721.pdf 2dbaba87e64d3ca99f811d955e64bf2a502d20617c56f9ba73368fbcbd461894 pmc_33321721.pdf Title: Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury Subject: Background: Ceftolozane-tazobactam is a new antibiotic against multidrug-resistant pathogens such as Pseudomonas aeruginosas. Ceftolozane-tazobactam dosage is still uncertain in children, especially in those with renal impairment or undergoing continuous renal replacement therapy (CRRT). Methods: Evaluation of different ceftolozane-tazobactam dosing regimens in three critically ill children. Ceftolozane pharmacokinetics (PK) were characterized by obtaining the patient’s specific parameters by Bayesian estimation based on a population PK model. The clearance (CL) in patient C undergoing CRRT was estimated using the prefilter, postfilter, and ultrafiltrate concentrations simultaneously. Variables such as blood, dialysate, replacement, and ultrafiltrate flow rates, and hematocrit were integrated in the model. All PK analyses were performed using NONMEM v.7.4. Results: Patient A (8 months of age, 8.7 kg) with normal renal function received 40 mg/kg every 6 h: renal clearance (CLR) was 0.88 L/h; volume of distribution (Vd) Vd1 = 3.45 L, Vd2 = 0.942 L; terminal halflife (t1/2,) = 3.51 h, dosing interval area under the drug concentration vs. time curve at steady-state (AUC,SS) 397.73 mg h L-1. Patient B (19 months of age, 11 kg) with eGFR of 22 mL/min/1.73 m2 received 36 mg/kg every 8 h: CLR = 0.27 L/h; Vd1 = 1.13 L; Vd2 = 1.36; t1/2, = 6.62 h; AUCSS 1481.48 mg h L-1. Patient C (9 months of age, 5.8 kg), with severe renal impairment undergoing CRRT received 30 mg/kg every 8 h: renal replacement therapy clearance (CLRRT) 0.39 L/h; Vd1 = 0.74 L; Vd2= 1.17; t 1/2, = 3.51 h; AUC,SS 448.72 mg h L-1. No adverse effects attributable to antibiotic treatment were observed. Conclusions: Our results suggest that a dose of 35 mg/kg every 8 h can be appropriate in critically ill septic children with multi-drug resistance Pseudomonas aeruginosa infections. A lower dose of 10 mg/kg every 8 h could be considered for children with severe AKI. For patients with CRRT and a high effluent rate, a dose of 30 mg/kg every 8 h can be considered. Keywords: ceftolozane; acute kidney injury; population pharmacokinetics; critically ill children; dose individualization; continuous renal replacement therapy Author: Laura Butragueño-Laiseca, Iñaki F. Troconiz, Santiago Grau, Nuria Campillo, Xandra García, Belén Padilla, Sarah N. Fernández and María José Santiago Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Thu Dec 10 06:39:41 2020 CET ModDate: Thu Dec 10 06:39:41 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 556281 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XJPOKS+URWPalladioL-Ital Type 1 Custom yes yes no 117 0 CXWOUD+URWPalladioL-Bold Type 1 Custom yes yes no 118 0 IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 119 0 YOOYPB+URWPalladioL-Roma Type 1 Custom yes yes no 120 0 PSUYZB+VnURWPalladioL Type 1 Custom yes yes no 121 0 DXFCOI+Rpxr Type 1 Builtin yes yes no 122 0 BKWOMT+EURM7 Type 1 Builtin yes yes no 123 0 FANYGL+Pxsy Type 1 Builtin yes yes no 124 0 YYFPCJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 130 0 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(Rel. 1.22.1, 2019-04-17) Date: 2023-10-17 02:24:02 CEST RepresentationInformation: pmc_33321721.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2020-12-28 03:46:23 CET Size: 556281 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 0 FreeObjects: 3 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: きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰こちねばぬどのでぜ〴ぜ〰ちのつぜ〴ぜ〰ぁのちぬべぴどっちぬぜ〴ぜ〰きづぴとはつぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰いちぴちぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: こちねばぬどのでぜ〴ぜ〰ちのつぜ〴ぜ〰ぁのちぬべぴどっちぬぜ〴ぜ〰きづぴとはつぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰いちぴちぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: いちぴちぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぐとちひねちっはつべのちねどっびぜ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⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐちぴどづのぴぜ〴ぜ〰ぃとちひちっぴづひどびぴどっび〬ぜ〴ぜ〰いはびどのでぜ〴ぜ〰ちのつぜ〴ぜ〰こちねばぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰はてぜ〴ぜ〰ぃづてぴはぬはぺちのづぜ〴ぜ〰どのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとはふぴぜ〴ぜ〰ぃはのぴどのふはふびぜ〴ぜ〰げづのちぬぜ〴ぜ〰げづばぬちっづねづのぴぜ〴ぜ〰ごとづひちばべぜ〴ぜ〰ぜ〵ぜ〰ぃげげごぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰はてぜ〴ぜ〰ぃづてぴはぬはぺちのづぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰えづねはつどちぬべぺづつぜ〴ぜ〰ぐちぴどづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: ぐちぴどづのぴぜ〴ぜ〰ぃとちひちっぴづひどびぴどっび〬ぜ〴ぜ〰いはびどのでぜ〴ぜ〰ちのつぜ〴ぜ〰こちねばぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰はてぜ〴ぜ〰ぃづてぴはぬはぺちのづぜ〴ぜ〰どのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとはふぴぜ〴ぜ〰ぃはのぴどのふはふびぜ〴ぜ〰げづのちぬぜ〴ぜ〰げづばぬちっづねづのぴぜ〴ぜ〰ごとづひちばべぜ〴ぜ〰ぜ〵ぜ〰ぃげげごぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰はてぜ〴ぜ〰ぃづてぴはぬはぺちのづぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰えづねはつどちぬべぺづつぜ〴ぜ〰ぐちぴどづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰はてぜ〴ぜ〰ぃづてぴはぬはぺちのづぜ〴ぜ〰どのぜ〴ぜ〰ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとはふぴぜ〴ぜ〰ぃはのぴどのふはふびぜ〴ぜ〰げづのちぬぜ〴ぜ〰げづばぬちっづねづのぴぜ〴ぜ〰ごとづひちばべぜ〴ぜ〰ぜ〵ぜ〰ぃげげごぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰はてぜ〴ぜ〰ぃづてぴはぬはぺちのづぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰えづねはつどちぬべぺづつぜ〴ぜ〰ぐちぴどづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰はてぜ〴ぜ〰ぃづてぴはぬはぺちのづぜ〴ぜ〰どのぜ〴ぜ〰ぴとづぜ〴ぜ〰えづねはつどちぬべぺづつぜ〴ぜ〰ぐちぴどづのぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㐩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ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⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぃげげごぜ〴ぜ〰ぃぬづちひちのっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ〴ぜ〰ちのつぜ〴ぜ〰ぁひづちぜ〴ぜ〰ふのつづひぜ〴ぜ〰ぃふひぶづぜ〴ぜ〰ぜ〵ぜ〰ぁさぃぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Children: Item: Title: ぃげげごぜ〴ぜ〰ぃぬづちひちのっづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ〴ぜ〰ちのつぜ〴ぜ〰ぁひづちぜ〴ぜ〰ふのつづひぜ〴ぜ〰ぃふひぶづぜ〴ぜ〰ぜ〵ぜ〰ぁさぃぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぐとちひねちっはつべのちねどっぜ〴ぜ〰ごちひでづぴぜ〴ぜ〰ちのつぜ〴ぜ〰ぁひづちぜ〴ぜ〰ふのつづひぜ〴ぜ〰ぃふひぶづぜ〴ぜ〰ぜ〵ぜ〰ぁさぃぜ〵ㅜ〰ぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸶ Item: Title: がどねどぴちぴどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸷ Item: Title: ぁつつづのつふねぜ〴ぜ〰ぴはぜ〴ぜ〰ぴとづぜ〴ぜ〰きちぴづひどちぬぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴ぜ〰こづっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㜮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぐはばふぬちぴどはのぜ〴ぜ〰ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰ぜ〵ぜ〰ぐかぜ〵ㅜ〰ぜ〴ぜ〰きはつづぬどのでぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸷⸱⸱ Children: Item: Title: ぐはばふぬちぴどはのぜ〴ぜ〰ぐとちひねちっはにどのづぴどっびぜ〴ぜ〰ぜ〵ぜ〰ぐかぜ〵ㅜ〰ぜ〴ぜ〰きはつづぬどのでぜ〴ぜ〰ぁのちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸷⸱⸱ Children: Item: Title: ぐちぴどづのぴびぜ〴ぜ〰ぷどぴとはふぴぜ〴ぜ〰えづねはつどちぬべびどびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸷⸱⸲ Item: Title: ぐちぴどづのぴぜ〴ぜ〰ぷどぴとぜ〴ぜ〰ぃげげごぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸷⸱⸳ Item: Title: ぅぶちぬふちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰きはつづぬどのでぜ〴ぜ〰げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸷⸱⸴ Item: Title: いづひどぶづつぜ〴ぜ〰ぐとちひねちっはにどのづぴどっぜ〴ぜ〰ぐちひちねづぴづひびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴひどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸷⸱⸵ Item: Title: ぃげげごぜ〴ぜ〰ぐちひちねづぴづひびぜ〴〩਼㰠⽓ 䝯呯 䐠⡥煵慴楯渮㜮ㄩ‾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: YOOYPB+URWPalladioL-Roma FontSubset: true FirstChar: 47 LastChar: 47 FontDescriptor: FontName: YOOYPB+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: MFIGJL+Rpxb FontSubset: true FirstChar: 47 LastChar: 47 FontDescriptor: FontName: MFIGJL+Rpxb Flags: Symbolic FontBBox: -57, -266, 932, 729 FontFile: true Font: BaseFont: OUGXGK+EURM10 FontSubset: true FirstChar: 12 LastChar: 33 FontDescriptor: FontName: OUGXGK+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: GIGFZE+CMR10 FontSubset: true FirstChar: 40 LastChar: 61 FontDescriptor: FontName: GIGFZE+CMR10 Flags: 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