Email this article Evaluation of plasma levels of meropenem in septic patients during extracorporeal blood purification
- Authors: Marukhov A.V.1, Murzina E.V.1, Zakharov M.V.1, Sofronov G.A.1,2, Buryakova L.V.1, Ivanov M.B.2, Zhurkovich I.K.2, Ostrovidova E.V.2
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Affiliations:
- S.M. Kirov Military Medical Academy of the Ministry of Defense of Russian Federation
- Institute of Toxicology of Federal Medical Biological Agency of Russia
- Issue: Vol 20, No 4 (2020)
- Pages: 81-94
- Section: Clinical research
- URL: https://journals.rcsi.science/MAJ/article/view/54636
- DOI: https://doi.org/10.17816/MAJ54636
- ID: 54636
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Abstract
The relevance. Meropenem is a broad-spectrum carbapenem antibiotic widely used to treat patients with sepsis / septic shock. Critically ill patients are usually supported with one of the forms extracorporeal blood purification. However, data on the effect of various extracorporeal support techniques on the pharmacokinetics and pharmacodynamics of meropenem are insufficient or contradictory.
Aim: To evaluate the effectiveness of meropenem dosage regimens in the treatment of septic patients during extracorporeal blood purification.
Materials and methods. Plasma concentrations of meropenem were monitored in three critically ill patients with sepsis or septic shock. Patients were treated using various extracorporeal support techniques. Meropenem was used as empirical antibacterial mono- or complex therapy (1 g every 8 or 12 hours). Meropenem concentrations in plasma were determined by validated assay methods on Acquity ultraefficient liquid chromatography (UPLC) H-Class system.
Results. It is shown that the meropenem plasma concentration in critically ill patients changes significantly. It was found that the standard meropenem dosing regimens in patients with sepsis / septic shock during continuous hemodiafiltration do not ensure the achievement of the PK/PD target of 100% T>MIC for sensitive strains (MIC≤2 mg/L) and for intermediate resistance pathogens (2≤MIC<8 mg/L). Continuous hemofiltration and selective adsorption of lipopolysaccharide have a less pronounced effect on the clearance of meropenem.
Conclusion. To increase the effectiveness of antibacterial therapy, it is necessary to conduct research aimed at developing protocols for dosing antibacterial drugs for the treatment of sepsis during extracorporeal blood purification.
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##article.viewOnOriginalSite##About the authors
Artem V. Marukhov
S.M. Kirov Military Medical Academy of the Ministry of Defense of Russian Federation
Email: maruxov84@mail.ru
SPIN-code: 6428-0402
PhD in Medicine, Head of Intensive Care Unit of the Department of Nephrology and Efferent Therapy
Russian Federation, Saint PetersburgElena V. Murzina
S.M. Kirov Military Medical Academy of the Ministry of Defense of Russian Federation
Author for correspondence.
Email: elenmurzina@mail.ru
ORCID iD: 0000-0001-7052-3665
SPIN-code: 5188-0797
PhD in Biology, Senior Researcher of Research Laboratory of Medicinal and Environmental Toxicology, Research Center
Russian Federation, Saint PetersburgMikhail V. Zakharov
S.M. Kirov Military Medical Academy of the Ministry of Defense of Russian Federation
Email: zamivlad@yandex.ru
SPIN-code: 4732-9877
PhD in Medicine, Deputy Head of the Department of Nephrology and Efferent Therapy
Russian Federation, Saint PetersburgGenrikh A. Sofronov
S.M. Kirov Military Medical Academy of the Ministry of Defense of Russian Federation; Institute of Toxicology of Federal Medical Biological Agency of Russia
Email: gasofronov@mail.ru
ORCID iD: 0000-0002-8587-1328
SPIN-code: 7334-4881
MD, PhD, Professor, Member of the RAS, Head of the Research Laboratory of Medicinal and Environmental Toxicology, Research Center; Scientific Supervisor
Russian Federation, Saint PetersburgLyudmila V. Buryakova
S.M. Kirov Military Medical Academy of the Ministry of Defense of Russian Federation
Email: ludmila.buryakova@yandex.ru
SPIN-code: 3355-9862
PhD in Biology, Research Fellow of Research Laboratory of Military Surgery
Russian Federation, Saint PetersburgMaxim B. Ivanov
Institute of Toxicology of Federal Medical Biological Agency of Russia
Email: m.b.ivanov@toxicology.ru
SPIN-code: 1895-7062
MD, PhD, Director of the Institute of Toxicology
Russian Federation, Saint PetersburgInna K. Zhurkovich
Institute of Toxicology of Federal Medical Biological Agency of Russia
Email: zhurkovich@toxicology.ru
PhD in Chemistry, Head of the Laboratory of Toxicological Chemistry of Organic Compounds of the Institute of Toxicology
Russian Federation, Saint PetersburgEkaterina V. Ostrovidova
Institute of Toxicology of Federal Medical Biological Agency of Russia
Email: yekaterina.ostrov@yandex.ru
Junior Researcher of the Laboratory of Toxicological Chemistry of Organic Compounds
Russian Federation, Saint PetersburgReferences
- Сухорукова М.В., Эйдельштейн М.В., Иванчик Н.В. и др. Антибиотикорезистентность нозокомиальных штаммов Enterobacterales в стационарах России: Результаты многоцентрового эпидемиологического исследования «Марафон 2015–2016» // Клиническая микробиология и антимикробная химиотерапия. – 2019. – Т. 21. – № 2. – С. 147–159. [Suhorukova MV, Ejdel’shtejn MV, Ivanchik NV, et al. Antimicrobial resistance of nosocomial Enterobacterales isolates in Russia: results of multicenter epidemiological study “Marathon 2015–2016”. Clinical Microbiology and Antimicrobial Chemotherapy. 2019;21(2):147–159. (In Russ.)]. https://doi.org/10.36488/cmac.2019.2.147-159.
- Эйдельштейн М.В., Шек Е.А., Сухорукова М.В. и др. Антибиотикорезистентность, продукция карбапенемаз и генотипы нозокомиальных штаммов Pseudomonas aeruginosa в стационарах России: Результаты многоцентрового эпидемиологического исследования «Марафон 2015–2016» // Клиническая микробиология и антимикробная химиотерапия. – 2019. – Т. 21. – № 2. – С. 160–170. [Ejdel’shtejn MV, Shek EA, Suhorukova MV, et al. Antimicrobial resistance, carbapenemase production, and genotypes of nosocomial Pseudomonas aeruginosa isolates in Russia: Results of multicenter epidemiological study “Marathon 2015-2016”. Clinical Microbiology and Antimicrobial Chemotherapy. 2019;21(2):160–170. (In Russ.)]. https://doi.org/10.36488/cmac.2019.2.160-170.
- Шек Е.А., Сухорукова М.В., Эйдельштейн М.В. и др. Антибиотикорезистентность, продукция карбапенемаз и генотипы нозокомиальных штаммов Acinetobacter spp. в стационарах России: Результаты многоцентрового эпидемиологического исследования «Марафон 2015–2016» // Клиническая микробиология и антимикробная химиотерапия. – 2019. – Т. 21. – № 2. – С. 171–180. [Shek EA, Suhorukova MV, Ejdel’shtejn MV, et al. Antimicrobial resistance, carbapenemase production, and genotypes of nosocomial Acinetobacter spp. isolates in Russia: results of multicenter epidemiological study “Marathon 2015-2016”. Clinical Microbiology and Antimicrobial Chemotherapy. 2019;21(2):171–180. (In Russ.)]. https://doi.org/10.36488/cmac.2019.2.171-180.
- Wu Y, Xu J. Analysis of the microbial species, antimicrobial sensitivity and drug resistance in 2652 patients of nursing hospital. Heliyon. 2020;6(5):e03965. https://doi.org/10.1016/j.heliyon.2020.e03965.
- Nicolau DP. Pharmacokinetic and pharmacodynamic properties of meropenem. Clin Infect Dis. 2008;47(1):32–40. https://doi.org/10.1086/590064.
- Ulldemolins M, Vaquer S, Llaurado-Serra M, et al. Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy. Crit Care. 2014;18(3):227. http://doi.org/10.1186/cc13938.
- Джекобс Ф. Новые подходы к оптимизации антимикробной терапии инфекций дыхательных путей с использованием фармакокинетических/фармакодинамических параметров // Клиническая микробиология и антимикробная химиотерапия. – 2004. – Т. 6. – № 1. – С. 22–31. [Dzhekobs F. New approaches to the optimization of antimicrobial therapy of respiratory tract infections using pharmacokinetic and pharmacodynamic parameters. Clinical Microbiology and Antimicrobial Chemotherapy. 2004;6(1):22–31. (In Russ.)]
- Roberts JA, Paul SK, Akova M, et al. DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014;58(8):1072–1083. http://doi.org/10.1093/cid/ciu027.
- De Waele JJ, Lipman J, Akova M, et al. Risk factors for target non-attainment during empirical treatment with beta-lactam antibiotics in critically ill patients. Intensive Care Med. 2014;40(9):1340–1351. https://doi.org/ 10.1007/s00134-014-3403-8.
- Li C, Du X, Kuti JL, Nicolau DP. Clinical pharmacodynamics of meropenem in patients with lower respiratory tract infections. Antimicrob Agents Chemother. 2007;51(5):1725–1730. http://doi.org/10.1128/AAC.00294-06.
- Burger R, Guidi M, Calpini V, et al. Effect of renal clearance and continuous renal replacement therapy on appropriateness of recommended meropenem dosing regimens in critically ill patients with susceptible life-threatening infection. J Antimicrob Chemother. 2018;73(12):3413–3422. https://doi.org/10.1093/jac/dky370.
- Zamora AP, Roig RJ, Badosa EL, et al. Optimized meropenem dosage regimens using a pharmacokinetic/pharmacodynamic population approach in patients undergoing continuous venovenous haemodiafiltration with high-adsorbent membrane. J Antimicrob Chemother. 2019;74(10):2979–2983. https://doi.org/10.1093/jac/dkz299.
- Европейский комитет по определению чувствительности к антимикробным препаратам. Таблицы пограничных значений для интерпретации значений МПК и диаметров зон подавления роста. Версия 10.0, 2020. [Evropejskij komitet po opredeleniyu chuvstvitel’nosti k antimikrobnym preparatam. Tablicy pogranichnyh znachenij dlya interpretacii znachenij MPK i diametrov zon podavleniya rosta. Versiya 10.0, 2020. (In Russ.)]. http://www.antibiotic.ru/iacmac/ru/info/eucast.shtml.
- Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009;37(3):840–851. https://doi.org/10.1097/CCM.0b013e3181961bff.
- Owen EJ, Gibson GA, Buckman SA. Pharmacokinetics and pharmacodynamics of antimicrobials in critically ill patients. Surg Infect (Larchnt). 2018;19(2):155–162. https://doi.org/10.1089/sur.2017.262.
- Esposito S, De Simone G, Boccia G, et al. Sepsis and septic shock: New definitions, new diagnostic and therapeutic approaches. J Glob Antimicrob Resist. 2017;10:204–212. https://doi.org/10.1016/j.jgar.2017.06.013.
- Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42(8):1749–1755. https://doi.org/10.1097/CCM.0000000000000330.
- Shaw AR, Mueller BA. Antibiotic dosing in continuous renal replacement therapy. Adv Chronic Kidney Dis. 2017;24(4):219–227. https://doi.org/10.1053/j.ackd.2017. 05.004.
- Jang SM, Infante S, Abdi Pour A. Drug dosing considerations in critically ill patients receiving continuous renal replacement therapy. Pharmacy (Basel). 2020;8(1):18. https://doi.org/10.3390/pharmacy8010018.
- Lewis SJ, Mueller BA. Antibiotic dosing in critically ill patients receiving crrt: underdosing is overprevalent. Semin Dial. 2014;27(5):441–445. https://doi.org/10.1111/sdi.12203.
- Hoff BM, Maker JH, Dager WE, Heintz BH. Antibiotic dosing for critically ill adult patients receiving intermittent hemodialysis, prolonged intermittent renal replacement therapy, and continuous renal replacement therapy: an update. Ann Pharmacother. 2020;54(1):43–55. https://doi.org/10.1177/1060028019865873.
- Li L, Li X, Xia Y, et al. Recommendation of antimicrobial dosing optimization during continuous renal replacement therapy. Front Pharmacol. 2020;11:786. https://doi.org/10.3389/fphar.2020.00786.
- Donadio C, Tognotti D, Caponi L, Paolicchi A. β-Trace protein is highly removed during haemodialysis with high-flux and super high-flux membranes. BMC Nephrol. 2017;18(1):68. https://doi.org/ 10.1186/s12882-017-0489-6.
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