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      Correlation between the drug concentration of polymyxin B and polymyxin B‐associated acute kidney injury in critically ill patients: A prospective study

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          Abstract

          In recent years, polymyxin B‐associated acute kidney injury (PB‐AKI) in critically ill patients has been reported frequently, but polymyxin B (PB) is mainly cleared through non‐renal pathways, and the reasons of PB‐AKI remain unclear. The aim of this study was to investigate the relationship between the serum concentration of PB and PB‐AKI. We conducted a prospective cohort study in an intensive care unit between May 2019 and July 2021. Over the study period, 52 patients were included and divided into an AKI group ( n = 26) and a non‐AKI group ( n = 26). The loading dose of PB in the AKI group was significantly higher than that in the non‐AKI group. The C 1/2, C min, and estimated area under the concentration–time curve (AUC) 0–24 of PB in the AKI group were dramatically increased compared with those in the non‐AKI group, but the C max between the two groups showed no differences. Upon obtaining the ROC curve, the areas for the C 1/2, C min, and estimated AUC 0–24 were 0.742, 0.710, and 0.710, respectively. The sensitivity was ascertained to be 61.54%, and the specificity was 76.92% when the cutoff value for the estimated AUC 0–24 of 97.72 mg·h/L was used preferentially. The incidence of PB‐AKI is high and related to the loading dose of PB. PB‐AKI could be predicted when the estimated AUC 0–24 of PB was greater than 97.72 mg·h/L.

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          Most cited references36

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          KDIGO Clinical Practice Guidelines for Acute Kidney Injury

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            Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections.

            The emergence of multidrug-resistant gram-negative bacteria and the lack of new antibiotics to combat them have led to the revival of polymyxins, an old class of cationic, cyclic polypeptide antibiotics. Polymyxin B and polymyxin E (colistin) are the 2 polymyxins used in clinical practice. Most of the reintroduction of polymyxins during the last few years is related to colistin. The polymyxins are active against selected gram-negative bacteria, including Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species. These drugs have been used extensively worldwide for decades for local use. However, parenteral use of these drugs was abandoned approximately 20 years ago in most countries, except for treatment of patients with cystic fibrosis, because of reports of common and serious nephrotoxicity and neurotoxicity. Recent studies of patients who received intravenous polymyxins for the treatment of serious P. aeruginosa and Acinetobacter baumannii infections of various types, including pneumonia, bacteremia, and urinary tract infections, have led to the conclusion that these antibiotics have acceptable effectiveness and considerably less toxicity than was reported in old studies.
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              International Consensus Guidelines for the Optimal Use of the Polymyxins

              The polymyxin antibiotics colistin (polymyxin E) and polymyxin B became available in the 1950s and thus did not undergo contemporary drug development procedures. Their clinical use has recently resurged, assuming an important role as salvage therapy for otherwise untreatable gram-negative infections. Since their reintroduction into the clinic, significant confusion remains due to the existence of several different conventions used to describe doses of the polymyxins, differences in their formulations, outdated product information, and uncertainties about susceptibility testing that has led to lack of clarity on how to optimally utilize and dose colistin and polymyxin B. We report consensus therapeutic guidelines for agent selection and dosing of the polymyxin antibiotics for optimal use in adult patients, as endorsed by the American College of Clinical Pharmacy (ACCP), Infectious Diseases Society of America (IDSA), International Society of Anti-Infective Pharmacology (ISAP), Society for Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) endorses this document as a consensus statement. The overall conclusions in the document are endorsed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). We established a diverse international expert panel to make therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, polymyxin agent selection, dosing, dosage adjustment and monitoring of colistin and polymyxin B, use of polymyxin-based combination therapy, intrathecal therapy, inhalation therapy, toxicity, and prevention of renal failure. The treatment guidelines provide the first ever consensus recommendations for colistin and polymyxin B therapy that are intended to guide optimal clinical use.
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                Author and article information

                Contributors
                xinyingwang2021@163.com
                Journal
                Pharmacol Res Perspect
                Pharmacol Res Perspect
                10.1002/(ISSN)2052-1707
                PRP2
                Pharmacology Research & Perspectives
                John Wiley and Sons Inc. (Hoboken )
                2052-1707
                07 October 2022
                October 2022
                : 10
                : 5 ( doiID: 10.1002/prp2.v10.5 )
                : e01010
                Affiliations
                [ 1 ] Surgical Intensive Care Unit (SICU), Department of General Surgery Jinling Hospital of Nanjing Medical University Nanjing China
                [ 2 ] Intensive Care Unit Drum Tower Hospital Affiliated to Nanjing University School of Medicine Nanjing Jiangsu China
                [ 3 ] Department of Pharmacy Drum Tower Hospital Affiliated to Nanjing University School of Medicine Nanjing China
                Author notes
                [*] [* ] Correspondence

                Xinying Wang, Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital of Nanjing Medical University, Nanjing, China.

                Email: xinyingwang2021@ 123456163.com

                Author information
                https://orcid.org/0000-0002-5485-2079
                Article
                PRP21010 PRP2-2022-06-0262.R2
                10.1002/prp2.1010
                9542723
                36206131
                08a2599a-8c2f-4a0b-bfd2-e643f8e936f6
                © 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 June 2022
                : 30 August 2022
                Page count
                Figures: 3, Tables: 4, Pages: 8, Words: 4834
                Funding
                Funded by: Medical Technology Development Project of Nanjing
                Award ID: YKK15055
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                October 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.0 mode:remove_FC converted:07.10.2022

                acute kidney injury,area under the concentration–time curve,critically ill patients,drug concentration,polymyxin

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