a9a14d51d657fec16a031378f8015d9b pmc_34204943.pdf 376272e3818516fb4a5b9ee11886a365cb06153f pmc_34204943.pdf f0d0ffa7ad8235b70bd6427df08a0a5149f2b91edfb97551c3371b36bea7d3a0 pmc_34204943.pdf Title: Pharmacokinetics and Pharmacodynamics of Meropenem by Extended or Continuous Infusion in Low Body Weight Critically Ill Patients Subject: Background: Pathophysiological changes such as extreme body weights in critically ill patients with severe infections may alter the pharmacokinetics (PK) of antimicrobials, leading to treatment failure or toxicity. There are almost no PK data on meropenem in critically ill patients with low body weight (LwBW) and therefore information is lacking on the most appropriate dosing regimens, especially when administered by extended infusion. Objectives: To assess if the current administered doses of meropenem could lead to supratherapeutic concentrations in LwBW patients and to identify the factors independently associated with overexposure. Methods: A matched case-control 1:1 study of surgical critically ill patients treated with meropenem administered by extended or continuous infusion and undergoing therapeutic drug monitoring was conducted. Cases (patients with LwBW (body mass index (BMI) < 18.5 kg/m2)) were matched with normal body weight controls (NBW) (patients with BMI 18.5 kg/m2 and 30 kg/m2)) by age, gender, baseline renal function and severity status (APACHE II score). A 100% fT > MIC was considered an optimal pharmacokinetic/pharmacodynamic (PK/PD) target and 100% fT > 10 MIC as supratherapeutic exposure. Results: Thirty-six patients (18 cases and 18 controls) were included (median (range) age, 57.5 (26–75) years; 20 (55.6% male)). Meropenem was administered by 6 h (extended) or 8 h (continuous) infusion at a median (range) daily dose of 5 (1–6) g/day. Similar median meropenem trough plasma concentrations (Cmin,ss), measured pre-dose on day three to four of treatment) were observed in the two groups (19.9 (22.2) mg/L vs 22.4 (25.8) mg/L, p > 0.999). No differences in the proportion of patients with an optimal or a supratherapeutic PKPD target between cases and controls were observed. A baseline estimated glomerular filtration rate (eGFR) < 90 mL/min was the only factor independently associated with a supratherapeutic PK/PD target. Conclusions: LwBW seems not to be a risk factor for achieving a supratherapeutic PK/PD target in critically ill patients receiving meropenem at standard doses by extended or continuous infusion. Keywords: antibiotics; pharmacokinetics; pharmacodynamics; low body weight; meropenem Author: Sonia Luque, Adela Benítez-Cano, Leire Larrañaga, Luisa Sorlí, María Eugenia Navarrete, Nuria Campillo, Jesús Carazo, Isabel Ramos, Ramón Adalia and Santiago Grau Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jun 3 09:55:19 2021 CEST ModDate: Thu Jun 3 09:57:13 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 713473 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FXKWJE+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 XRRZYO+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 RJCUNE+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 BKROAZ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 NWYVYM+CMSY10 Type 1 Builtin yes yes no 28 0 YYFPCJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 37 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 59 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 63 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 67 0 VXEOOM+VnURWPalladioL Type 1 Custom yes yes no 79 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 83 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 93 0 PNAFEO+Calibri CID TrueType Identity-H yes yes yes 109 0 PNACOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 115 0 PNACOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 118 0 PNACOH+PalatinoLinotype TrueType WinAnsi yes yes no 124 0 PNACOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 127 0 PNAEPP+TimesNewRoman CID TrueType Identity-H yes yes yes 130 0 PNAFEO+Calibri CID TrueType Identity-H yes yes yes 147 0 PNACOF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 153 0 PNACOG+PalatinoLinotype CID TrueType Identity-H yes yes yes 156 0 PNACOH+PalatinoLinotype TrueType WinAnsi yes yes no 162 0 PNACOJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 165 0 PNAEPP+TimesNewRoman CID TrueType Identity-H yes yes yes 168 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-10-21 02:37:09 CEST RepresentationInformation: pmc_34204943.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:14:19 CEST Size: 713473 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 309 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Material and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Setting and Study Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Study Protocol Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Dosing Regimen and PK Sampling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Pharmacokinetic/Pharmacodynamics (PK/PD) Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Info: Title: Pharmacokinetics and Pharmacodynamics of Meropenem by Extended or Continuous Infusion in Low Body Weight Critically Ill Patients Author: Sonia Luque, Adela Benítez-Cano, Leire Larrañaga, Luisa Sorlí, María Eugenia Navarrete, Nuria Campillo, Jesús Carazo, Isabel Ramos, Ramón Adalia and Santiago Grau Subject: Background: Pathophysiological changes such as extreme body weights in critically ill patients with severe infections may alter the pharmacokinetics (PK) of antimicrobials, leading to treatment failure or toxicity. There are almost no PK data on meropenem in critically ill patients with low body weight (LwBW) and therefore information is lacking on the most appropriate dosing regimens, especially when administered by extended infusion. Objectives: To assess if the current administered doses of meropenem could lead to supratherapeutic concentrations in LwBW patients and to identify the factors independently associated with overexposure. Methods: A matched case-control 1:1 study of surgical critically ill patients treated with meropenem administered by extended or continuous infusion and undergoing therapeutic drug monitoring was conducted. Cases (patients with LwBW (body mass index (BMI) < 18.5 kg/m2)) were matched with normal body weight controls (NBW) (patients with BMI 18.5 kg/m2 and 30 kg/m2)) by age, gender, baseline renal function and severity status (APACHE II score). A 100% fT > MIC was considered an optimal pharmacokinetic/pharmacodynamic (PK/PD) target and 100% fT > 10 MIC as supratherapeutic exposure. Results: Thirty-six patients (18 cases and 18 controls) were included (median (range) age, 57.5 (26 75) years; 20 (55.6% male)). Meropenem was administered by 6 h (extended) or 8 h (continuous) infusion at a median (range) daily dose of 5 (1 6) g/day. Similar median meropenem trough plasma concentrations (Cmin,ss), measured pre-dose on day three to four of treatment) were observed in the two groups (19.9 (22.2) mg/L vs 22.4 (25.8) mg/L, p > 0.999). No differences in the proportion of patients with an optimal or a supratherapeutic PKPD target between cases and controls were observed. A baseline estimated glomerular filtration rate (eGFR) < 90 mL/min was the only factor independently associated with a supratherapeutic PK/PD target. Conclusions: LwBW seems not to be a risk factor for achieving a supratherapeutic PK/PD target in critically ill patients receiving meropenem at standard doses by extended or continuous infusion. 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