vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2022-447vedomostiregmed-447Research ArticleАНТИБАКТЕРИАЛЬНЫЕ ПРЕПАРАТЫANTIBACTERIAL DRUGSГликопептидные антибиотики: структурно-функциональные аспекты, применение в медицине и стандартизацияGlycopeptide Antibiotics: Structural and Functional Aspects, Human Medicinal Use, and Standardisationhttps://orcid.org/0000-0003-4327-6640ВысочанскаяО. Н.VysochanskayaO. N.

Высочанская Ольга Николаевна

Петровский б-р, д. 8, стр. 2, Москва, 127051

Olga N. Vysochanskaya

8/2 Petrovsky Blvd, Moscow 127051

visochanskayon@expmed.ruhttps://orcid.org/0000-0002-9103-9239КулешоваС. И.KuleshovaS. I.

Кулешова Светлана Ивановна, канд. биол. наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Svetlana I. Kuleshova, Cand. Sci. (Biol.)

8/2 Petrovsky Blvd, Moscow 127051

Kuleshova@expmed.ruhttps://orcid.org/0000-0002-2221-5534СимоноваЕ. П.SimonovaE. P.

Симонова Елена Павловна

Петровский б-р, д. 8, стр. 2, Москва, 127051

Elena P. Simonova

8/2 Petrovsky Blvd, Moscow 127051

SimonovaE@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation202308092022132-1261270Copyright © Высочанская О.Н., Кулешова С.И., Симонова Е.П., 20232023Высочанская О.Н., Кулешова С.И., Симонова Е.П.Vysochanskaya O.N., Kuleshova S.I., Simonova E.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/447

В последние годы для лечения тяжелых бактериальных инфекций широко применяются гликопептидные антибиотики. Длительное использование в медицинской практике антибиотиков первого поколения этой группы соединений (ванкомицин и тейкопланин) способствовало появлению устойчивых к ним бактерий. Для решения проблемы резистентности были разработаны три новых гликопептидных антибиотика: далбаванцин, телаванцин и оритаванцин.

Цель работы:  анализ и обобщение данных литературы и действующих стандартов качества, касающихся антибиотиков гликопептидной природы.

В работе приведены основные сведения об истории открытия антибиотиков-гликопептидов природного происхождения (ванкомицин, тейкопланин) и их производных (телаванцин, оритаванцин, далбаванцин). Охарактеризована структура гликопептидных антибиотиков, описаны их основные свойства, применение и распространение на фармацевтическом рынке. Приведена информация о спектре антибактериальной активности ванкомицина, тейкопланина и их полусинтетических производных. Рассмотрены подходы к стандартизации ванкомицина и тейкопланина, приведены основные требования ведущих фармакопей к качеству ванкомицина, тейкопланина и препаратов на их основе. Проведенное исследование показало, что гликопептидные антибиотики продолжают оставаться крайне востребованными благодаря высокой эффективности при лечении заболеваний, вызванных грамположительными бактериями. Однако на настоящий момент разработаны и введены в ведущие зарубежные фармакопеи стандарты качества только на два представителя этой группы антибиотиков: ванкомицин и тейкопланин. Обобщение данных литературных источников показало, что дальнейшая разработка модификаций гликопептидных антибиотиков направлена на создание соединений, характеризующихся пролонгированным действием и большей эффективностью действия против патогенных микроорганизмов. Таким образом, внимание исследователей должно быть направлено на дальнейшую стандартизацию новейших производных гликопептидных антибиотиков: телаванцин, оритаванцин и далбаванцин.

In recent years, glycopeptide antibiotics have been widely used to treat severe bacterial infections. The long-term use of first-generation antibiotics of this group (vancomycin, teicoplanin) has contributed to the emergence of bacteria resistant to them. The problem of resistance has motivated the development of three new glycopeptide antibiotics: dalbavancin, telavancin, and oritavancin. The aim of this study was to consolidate and analyse the data from literature and current quality standards related to glycopeptide antibiotics. The article presents basic information about the discovery of glycopeptide antibiotics of natural origin (vancomycin, teicoplanin) and their derivatives (telavancin, oritavancin, dalbavancin). It briefly characterises the structures of the glycopeptide antibiotics under consideration and describes their main properties, application, and distribution in the pharmaceutical market. The article also gives information on the spectra of antibacterial activity of vancomycin, teicoplanin, and their semi-synthetic derivatives. It considers approaches to vancomycin and teicoplanin standardisation and covers the main requirements of leading pharmacopoeias for the quality of vancomycin, teicoplanin, and the corresponding medicinal products. According to the study results, glycopeptide antibiotics are still widely prescribed because of their high effectiveness in diseases caused by Gram-positive bacteria. However, at present, leading pharmacopoeias have developed and implemented quality standards only for two antibiotics of the group: vancomycin and teicoplanin. According to the results of literature consolidation, further modification of glycopeptide antibiotics is aimed at creating compounds characterised by prolonged action and greater effectiveness against pathogenic microorganisms. Thus, the attention of researchers should be directed to further standardisation of the newest derivatives of glycopeptide antibiotics: telavancin, oritavancin, and dalbavancin.

гликопептидные антибиотикиванкомицинтейкопланинтелаванциноритаванциндалбаванцинструктурамеханизм антибактериального действияспектр антибактериального действиястандартизацияglycopeptide antibioticsvancomycinteicoplanintelavancinoritavancindalbavancinstructuremechanism of antibacterial actionspectrum of antibacterial actionstandardisationРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00001-22-00 на проведение прикладных научных исследований (номер государственного учета НИР 121021800098-4).The study reported in this publication was carried out as part of publicly funded research project No. 056-00001-22-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No.121021800098-4).ReferencesLevin DP. Vancomycin: a history. Clin Infect Dis. 2006;42 Suppl 1:S5–12. https://doi.org/10.1086/491709Levin DP. Vancomycin: a history. Clin Infect Dis. 2006;42 Suppl 1:S5–12. https://doi.org/10.1086/491709Phillips-Jones MK, Lithgo R, Dinu V, Gillis RB, Harding JE, Adams GG, Harding SE. Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration. Sci Rep. 2017;7(1):12697. https://doi.org/10.1038/s41598-017-12620-zPhillips-Jones MK, Lithgo R, Dinu V, Gillis RB, Harding JE, Adams GG, Harding SE. Full hydrodynamic reversibility of the weak dimerization of vancomycin and elucidation of its interaction with VanS monomers at clinical concentration. Sci Rep. 2017;7(1):12697. https://doi.org/10.1038/s41598-017-12620-zZeng D, Debabov D, Hartsell TL, Cano RJ, Adams S, Schuyler JA, et al. Approved glycopeptide antibacterial drugs: mechanism of action and resistance. Cold Spring Harb Perspect Med. 2016;6(12):a026989. https://doi.org/10.1101/cshperspect.a026989Zeng D, Debabov D, Hartsell TL, Cano RJ, Adams S, Schuyler JA, et al. Approved glycopeptide antibacterial drugs: mechanism of action and resistance. Cold Spring Harb Perspect Med. 2016;6(12):a026989. https://doi.org/10.1101/cshperspect.a026989Lambert M. IDSA Guidelines on the treatment of MRSA infections in adults and children. Am Fam Physician. 2011;84(4):455–63.Lambert M. IDSA Guidelines on the treatment of MRSA infections in adults and children. Am Fam Physician. 2011;84(4):455–63.Блатун ЛА, Крутиков МГ, Гришина ИА, Бобровников АЕ, Алексеев АА, Светухин АМ, Яковлев ВП. Клинико-лабораторная оценка эффективности ванкомицина (эдицин) при лечении гнойных ран кожи и мягких тканей, ожоговых ран и инфекционных осложнений ожоговой болезни. Антибиотики и химиотерапия. 2000;45(2):22–7.Blatun LA, Krutikov MG, Grishina IA, Bobrovnikov AE, Alekseev AA, Svetukhin AM. Clinical and laboratory evaluation of vancomycin (Edicin®) efficacy in the treatment of purulent wounds of the skin and soft tissues, burn wounds and infectious complications of burn disease. Antibiotiki i khimioterapiya = Antibiotics and Chemotherapy. 2000;45(2):22–7 (In Russ.)Barna JC, Williams DH, Strazzolini P, Malabarba A, Leung TW. Structure and conformation of epimers derived from the antibiotic teicoplanin. J Antibiot (Tokyo). 1984;37(10):1204–8. https://doi.org/10.7164/antibiotics.37.1204Barna JC, Williams DH, Strazzolini P, Malabarba A, Leung TW. Structure and conformation of epimers derived from the antibiotic teicoplanin. J Antibiot (Tokyo). 1984;37(10):1204–8. https://doi.org/10.7164/antibiotics.37.1204Borghi А, Coronelli C, Faniuolo L, Allievi G, Pallanza R, Gallo GG. Teichomycins, new antibiotics from actinoplanes teichomyceticus nov. sp. IV. Separation and characterization of the components of teichomycin (teicoplanin). J Antibiot (Tokyo). 1984;37(6):615–20. https://doi.org/10.7164/antibiotics.37.615Borghi А, Coronelli C, Faniuolo L, Allievi G, Pallanza R, Gallo GG. Teichomycins, new antibiotics from actinoplanes teichomyceticus nov. sp. IV. Separation and characterization of the components of teichomycin (teicoplanin). J Antibiot (Tokyo). 1984;37(6):615–20. https://doi.org/10.7164/antibiotics.37.615Mackay JP, Gerhard U, Beauregard DA, Westwell MS, Searle MS, Williams DH. Glycopeptide antibiotic activity and the possible role of dimerization: a model for biological signaling. J Am Chem Soc. 1994;116(11):4581–90. https://doi.org/10.1021/ja00090a006Mackay JP, Gerhard U, Beauregard DA, Westwell MS, Searle MS, Williams DH. Glycopeptide antibiotic activity and the possible role of dimerization: a model for biological signaling. J Am Chem Soc. 1994;116(11):4581–90. https://doi.org/10.1021/ja00090a006Дмитриева НВ, Петухова ИН, Григорьевская ЗВ, Багирова НС, Терещенко ИВ, Ключникова ИА, Дьякова СА. Cравнительный анализ активности гликопептидов и линезолида в отношении нозокомиальных штаммов грамположительных микроорганизмов, выделенных от онкологических пациентов. Сибирский онкологический журнал. 2021;20(5):93–9 https://doi.org/10.21294/1814-4861-2021-20-5-93-99Dmitrieva NV, Petukhova IN, Grigoryevskaya ZV, Bagirova NS, Tereshchenko IV, Klyuchnikova IA, Dyakova SA. Comparative analysis of the activity of glycopeptides and linezolid against nosocomial strains of gram-positive microorganisms isolated from cancer patient. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology. 2021;20(5):93–9 (In Russ.) https://doi.org/10.21294/1814-4861-2021-20-5-93-99Harding I, Sorgel F. Comparative pharmacokinetics of teicoplanin and vancomycin. J Chemother. 2000;12 Suppl 5:15–20. https://doi.org/10.1080/1120009X.2000.11782313Harding I, Sorgel F. Comparative pharmacokinetics of teicoplanin and vancomycin. J Chemother. 2000;12 Suppl 5:15–20. https://doi.org/10.1080/1120009X.2000.11782313Lewis P, Garaud JJ, Parenti F. A multicentre open clinical trial of teicoplanin in infections caused by Gram-positive bacteria, J Antimicrob Chemother. 1988;21(Suppl A):61–7. https://doi.org/10.1093/jac/21.suppl_a.61Lewis P, Garaud JJ, Parenti F. A multicentre open clinical trial of teicoplanin in infections caused by Gram-positive bacteria, J Antimicrob Chemother. 1988;21(Suppl A):61–7. https://doi.org/10.1093/jac/21.suppl_a.61Svetitsky S, Leibovici L, Paul M. Comparative efficacy and safety of vancomycin versus teicoplanin: systematic review and meta-analysis. Antimicrob Agents Chemother. 2009;53(10):4069–79. https://doi.org/10.1128/aac.00341-09Svetitsky S, Leibovici L, Paul M. Comparative efficacy and safety of vancomycin versus teicoplanin: systematic review and meta-analysis. Antimicrob Agents Chemother. 2009;53(10):4069–79. https://doi.org/10.1128/aac.00341-09Van Bambeke F. Glycopeptides in clinical development: pharmacological profile and clinical perspectives. Curr Opin Pharmacol. 2004;4(5):471–8. https://doi.org/10.1016/j.coph.2004.04.006Van Bambeke F. Glycopeptides in clinical development: pharmacological profile and clinical perspectives. Curr Opin Pharmacol. 2004;4(5):471–8. https://doi.org/10.1016/j.coph.2004.04.006Nawar T, Kanafani ZA. Telavancin (VIBATIV) for the treatment of complicated skin and skin structure infections. Expert Rev Anti Infect Ther. 2015;13(7):825–33. https://doi.org/10.1586/14787210.2015.1043889Nawar T, Kanafani ZA. Telavancin (VIBATIV) for the treatment of complicated skin and skin structure infections. Expert Rev Anti Infect Ther. 2015;13(7):825–33. https://doi.org/10.1586/14787210.2015.1043889Markham A. Oritavancin: first global approval. Drugs. 2014;74(15):1823–8. https://doi.org/10.1007/s40265-014-0295-4Markham A. Oritavancin: first global approval. Drugs. 2014;74(15):1823–8. https://doi.org/10.1007/s40265-014-0295-4Zhanel GG, Calic D, Schweizer F, Zelenitsky S, Adam H, Lagace-Wiens PRS, et al. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs. 2010;70(7):859–86. https://doi.org/10.2165/11534440-000000000-00000Zhanel GG, Calic D, Schweizer F, Zelenitsky S, Adam H, Lagace-Wiens PRS, et al. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs. 2010;70(7):859–86. https://doi.org/10.2165/11534440-000000000-00000Smith JR, Roberts KD, Rybak MJ. Dalbavancin: a novel lipoglycopeptide antibiotic with extended activity against gram-positive infections. Infect Dis Ther. 2015;4(3):245–58. https://doi.org/10.1007/s40121-015-0077-7Smith JR, Roberts KD, Rybak MJ. Dalbavancin: a novel lipoglycopeptide antibiotic with extended activity against gram-positive infections. Infect Dis Ther. 2015;4(3):245–58. https://doi.org/10.1007/s40121-015-0077-7Павлов АЮ, Преображенская МН. Химическая модификация гликопептидных антибиотиков. Биоорганическая химия. 1998;24(9):644–62.Pavlov AYu, Preobrazhenskaya MN. Chemical modification of glycopeptide antibiotics. Bioorganicheskaya khimiya = Bioorganic Chemistry. 1998;24(9):644–62 (In Russ.)Kahne D, Leimkuhler C, Lu W, Walsh Ch. Glycopeptide and lipoglycopeptide antibiotics, Chem Rev. 2005; 105(2):425–48. https://doi.org/10.1021/cr030103aKahne D, Leimkuhler C, Lu W, Walsh Ch. Glycopeptide and lipoglycopeptide antibiotics, Chem Rev. 2005; 105(2):425–48. https://doi.org/10.1021/cr030103aSieradzki K, Tomasz A. Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus. J Bacteriol. 1997;179(8):2557–66. https://doi.org/10.1128/jb.179.8.2557-2566.1997Sieradzki K, Tomasz A. Inhibition of cell wall turnover and autolysis by vancomycin in a highly vancomycin-resistant mutant of Staphylococcus aureus. J Bacteriol. 1997;179(8):2557–66. https://doi.org/10.1128/jb.179.8.2557-2566.1997Beauregard DA, Williams DH, Gwynn MN, Knowles DJ. Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics. Antimicrob Agents Chemother. 1995;39(3):781–5. https://doi.org/10.1128/aac.39.3.781Beauregard DA, Williams DH, Gwynn MN, Knowles DJ. Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics. Antimicrob Agents Chemother. 1995;39(3):781–5. https://doi.org/10.1128/aac.39.3.781Lunde CS, Hartouni SR, Janc JW, Mammen M, Humphrey PP, Benton BM. Telavancin disrupts the functional integrity of the bacterial membrane through targeted interaction with the cell wall precursor Lipid II. Antimicrob Agents Chemother. 2009;53(8):3375–83. https://doi.org/10.1128/aac.01710-08Lunde CS, Hartouni SR, Janc JW, Mammen M, Humphrey PP, Benton BM. Telavancin disrupts the functional integrity of the bacterial membrane through targeted interaction with the cell wall precursor Lipid II. Antimicrob Agents Chemother. 2009;53(8):3375–83. https://doi.org/10.1128/aac.01710-08

The authors declare that there are no conflicts of interest present.