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      The Determination of Polymyxin B in Critically Ill Patients by the HPLC-MS/MS Method

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          Abstract

          Polymyxin B (PB) is a dose-dependent drug used to treat multidrug-resistantgram-negative bacteria, for which a suitable method is needed to determine clinical samples. A simple, economical, and efficient high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was developed and validated for polymyxin B1 (PB1), polymyxin B1-Ile (PB1-I), polymyxin B2 (PB2), and polymyxin B3 (PB3) in human plasma. Chromatographic column was Waters BEH C18 column (2.1 × 50 mm, 1.7 μm). Phase A was water with 0.2% formic acid (FA), and phase B was acetonitrile containing 0.2% FA. The elution method is gradient elutio. The total analysis time was 5 min. The pretreatment method involved protein precipitation using acetonitrile containing 0.2% trifluoroacetic acid and 0.1% FA as the precipitant. The recovery rate was 92–99%. The total quantity of PB1 and PB1-I was measured in the linear range of 100–8000 ng/mL. Simultaneously, the total amounts of PB2 and PB3 were measured in the linear range of 11.9–948.5 ng/mL. This validated method was successfully applied to the pharmacokinetics of PB in critically ill patients.

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          Polymyxins revisited.

          John Quale, Larry D. Martin, Claudiu A Georgescu … (2008)
          The global emergence of multidrug-resistant gram-negative bacilli has spurred a renewed interest in polymyxins. Once discarded due to concerns regarding nephrotoxicity and neurotoxicity, polymyxins now hold an important role in the antibiotic armamentarium. However, more reliable information is needed to determine the optimal dosing of these agents. Also, unanswered questions regarding in vitro testing remain, including questions regarding the reliability of automated systems and the establishment of appropriate breakpoints for defining susceptibility. Most contemporary clinical studies examining the use of these agents have involved patients with infections due to multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii strains. It has been reassuring that polymyxin therapy for resistant bacteria has resulted in clinical responses and toxicity rates similar to those for carbapenem therapy for susceptible isolates. While most surveillance studies demonstrated high rates of susceptibility, several reports noted the emergence of polymyxin-resistant nosocomial pathogens. Polymyxins have assumed an important antibiotic niche for therapy for hospital-acquired infections; further studies defining the optimal use of these agents will likely extend the duration of their clinical usefulness.
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            Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review.

            A. Zavascki, L Z Goldani, J. Li … (2007)
            Polymyxins have re-emerged in clinical practice owing to the dry antibiotic development pipeline and worldwide increasing prevalence of nosocomial infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Polymyxin B and colistin (polymyxin E) have been ultimately considered as the last-resort treatment of such infections. Microbiological, pharmacokinetic, pharmacodynamic and clinical data available for polymyxin B are reviewed in this paper. Polymyxin B has rapid in vitro bactericidal activity against major MDR Gram-negative bacteria, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Acquired resistance to this agent is still rare among these pathogens. However, optimized dosage regimens are not known yet. Good clinical outcomes have been observed in the majority of the patients treated with intravenous polymyxin B in recent studies. However, these studies failed to provide definitive conclusions due to limitations of study design and additional clinical trials are required. Although combination therapy may be an attractive option based on some currently available in vitro data, clinical data supporting such recommendations are lacking. Since polymyxins will be increasingly used for the treatment of infections caused by MDR bacteria, clinical pharmacokinetic, pharmacodynamic and toxicodynamic studies underpinning the optimal use of these drugs are urgently required.
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              Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus.

              Roger Nation, Jian Li, Otto Cars … (2015)
              In the face of diminishing therapeutic options for the treatment of infections caused by multidrug-resistant, Gram-negative bacteria, clinicians are increasingly using colistin and polymyxin B. These antibiotics became available clinically in the 1950s, when understanding of antimicrobial pharmacology and regulatory requirements for approval of drugs was substantially less than today. At the 1st International Conference on Polymyxins in Prato, Italy, 2013, participants discussed a set of key objectives that were developed to explore the factors affecting the safe and effective use of polymyxins, identify the gaps in knowledge, and set priorities for future research. Participants identified several factors that affect the optimum use of polymyxins, including: confusion caused by several different conventions used to describe doses of colistin; an absence of appropriate pharmacopoeial standards for polymyxins; outdated and diverse product information; and uncertainties about susceptibility testing and breakpoints. High-priority areas for research included: better definition of the effectiveness of polymyxin-based combination therapy compared with monotherapy via well designed, randomised controlled trials; examination of the relative merits of colistin versus polymyxin B for various types of infection; investigation of pharmacokinetics in special patient populations; and definition of the role of nebulised polymyxins alone or in combination with intravenous polymyxins for the treatment of pneumonia. The key areas identified provide a roadmap for action regarding the continued use of polymyxins, and are intended to help with the effective and safe use of these important, last-line antibiotics.
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                Author and article information

                Contributors
                Xipei Wang:
                ORCID: https://orcid.org/0000-0002-2017-7247
                Chunbo Chen:
                ORCID: https://orcid.org/0000-0001-5662-497X
                Journal
                Journal ID (nlm-ta): Int J Anal Chem
                Journal ID (iso-abbrev): Int J Anal Chem
                Journal ID (publisher-id): ijac
                Title: International Journal of Analytical Chemistry
                Publisher: Hindawi
                ISSN (Print): 1687-8760
                ISSN (Electronic): 1687-8779
                Publication date Collection: 2023
                Publication date (Electronic): 7 April 2023
                Volume: 2023
                Electronic Location Identifier: 6674009
                Affiliations
                1School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, Guangdong, China
                2Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
                3Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China
                4Center of Scientific Research, Maoming People's Hospital, Maoming 525000, China
                5School of Medicine, South China University of Technology, Guangzhou 510006, China
                6Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
                7Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
                8Department of Critical Care Medicine, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of South University of Science and Technology, Shenzhen 518020, China
                9Department of Emergency, Maoming People's Hospital, Maoming 525000, China
                Author notes

                Academic Editor: Jiu-Ju Feng

                Author information
                https://orcid.org/0000-0002-8836-7565
                https://orcid.org/0000-0001-7862-1817
                https://orcid.org/0000-0002-2017-7247
                https://orcid.org/0000-0001-5662-497X
                Article
                DOI: 10.1155/2023/6674009
                PMC ID: 10104742
                SO-VID: 07ce5ecf-c9f3-4a8a-9260-04b34ed86a24
                Copyright statement: Copyright © 2023 Yirong Wang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 24 December 2022
                Date revision received : 20 February 2023
                Date accepted : 7 March 2023
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 82172162
                Funded by: Guangzhou Science and Technology Program key projects
                Award ID: 202002030317
                Funded by: Basic and Applied Basic Research Foundation of Guangdong Province
                Award ID: 21202104030001419
                Funded by: Office of Talent Work Leading Team in Maoming
                Award ID: 200221115835503
                Funded by: Science and Technology Planning Project of Guangdong Province
                Award ID: 2021S0024
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Analytical chemistry
                Data availability:
                ScienceOpen disciplines: Analytical chemistry

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