Antimicrobial activity of polyhexamethylene guanidine hydrochloride derivatives against multiresistant microbial strains

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Abstract

The resistance of bacteria to the disinfectants used is one of the pressing health problems requiring to be addressed in order to prevent formation and spread of resistant strains. Bacterial resistance leads to a sharply decreased effectiveness of anti-epidemic measures and contributes to maintaining a high morbidity level. In the context of the growing HAI incidence rate and related polyetiology, the large adaptive potential of opportunistic microorganisms, and the growing resistance to antimicrobial drugs, it is necessary to search for new or modify the corresponding substances of plant or synthetic origin exerting antimicrobial action used as antimicrobial agents. One of the representatives of this class of compounds are polyguanidines, characterized by high antimicrobial activity and low toxicity. Due to the high reactivity of the guanidine group, as well as ease of synthesis and relative availability of raw materials, N-phenyl- and N-octyl-substituted derivatives of polyhexamethylene guanidine hydrochloride were able to be obtained by melt polycondensation, their molecular weight characteristics were measured as well as the structure investigated by IR spectroscopy. An earlier study on the acute toxicity for polyhexamethylene guanidine hydrochloride derivatives after a single oral drug intake in laboratory animals (white mice) allowed to establish the following LD50 values: polyhexamethylene guanidine hydrochloride — 850.0±112.02 mg/ kg; N-phenyl-substituted polyhexamethylene guanidine hydrochloride — 1399.9±120.51 mg/kg; N-octyl-substituted polyhexamethylene guanidine hydrochloride — 1150.0±137.40 mg/kg. Such values, according to the tabulation of hazard classes, allow the synthesized derivatives to be classified into the fourth hazard class and open up an opportunity for using disinfectants as active components. The evaluation of the antibacterial sample properties was carried out by using serial dilutions in agar on hospital bacterial and fungal strains isolated from the biomaterial of patients at the Republican Clinical Hospital named after V.I. Semashko, according to the clinical guidelines “Laboratory diagnosis of community-acquired pneumonia” 2014, “Bacteriological analysis of urine” 2014, “Determination of the susceptibility of microorganisms to antimicrobial drugs” 2015. It was found that N-substituted derivatives exhibit a greater antimicrobial effect compared with unsubstituted polymer. The most sensitive to all the drugs presented was the yeast-like fungi Candida albicans (No. 2495) (complete suppression), as well as methicillin-resistant S. aureus (no. 2544), and the substituted samples almost completely suppress its growth. The most resistant strains are P. aeruginosa (No. 2281), A. baumannii (No. 2806) and K. pneumoniae (No. 3023), the percentage of reduction of these bacteria under the action of substituted samples does not exceed 41%, which is accounted for by their multi-resistance.

About the authors

O. S. Ochirov

Baikal Institute of Nature Management of the Siberian Branch of the Russian Academy of Sciences

Author for correspondence.
Email: ochirov.o.s@yandex.ru
ORCID iD: 0000-0002-2317-4105

Oleg S. Ochirov - PhD (Pharmacology), Leading Engineer, Laboratory of Polymer Science, Baikal Institute of Nature Management of the Siberian Branch of the RAS.

670047, Republic of Buryatia, Ulan-Ude, Sakhyanova str., 6.

Phone: +7 983 531-42-42.

Russian Federation

E. G. Burasova

Republican Clinical Hospital named after N.A. Semashko

Email: baklab2013@yandex.ru
ORCID iD: 0000-0002-2367-4089

Board Certified Bacteriologist, Head of the Bacteriological Laboratory, Republican Clinical Hospital named after N.A. Semashko.

Ulan-Ude, The Republic of Buryatia.

Russian Federation

S. A. Stelmakh

Baikal Institute of Nature Management of the Siberian Branch of the Russian Academy of Sciences

Email: S_stelmakh@bk.ru
ORCID iD: 0000-0003-3392-5600

PhD (Chemistry), Senior Researcher, Laboratory of Polymer Science, Baikal Institute of Nature Management of the Siberian Branch of the RAS.

670047, Republic of Buryatia, Ulan-Ude, Sakhyanova str., 6.

Russian Federation

M. N. Grigor'eva

Baikal Institute of Nature Management of the Siberian Branch of the Russian Academy of Sciences

Email: Gmn_07@bk.ru
ORCID iD: 0000-0003-4184-2805

PhD (Chemistry), Leading Engineer, Laboratory of Polymer Science, Baikal Institute of Nature Management of the Siberian Branch of the RAS.

670047, Republic of Buryatia, Ulan-Ude, Sakhyanova str., 6.

Russian Federation

V. O. Okladnikova

Baikal Institute of Nature Management of the Siberian Branch of the Russian Academy of Sciences

Email: lera-okladnikova@mail.ru
ORCID iD: 0000-0002-0903-8780

Engineer, Laboratory of Polymer Science, Baikal Institute of Nature Management of the Siberian Branch of the RAS.

670047, Republic of Buryatia, Ulan-Ude, Sakhyanova str., 6.

Russian Federation

D. M. Mognonov

Baikal Institute of Nature Management of the Siberian Branch of the Russian Academy of Sciences

Email: dmog@binm.ru
ORCID iD: 0000-0003-3562-6284

PhD, MD (Chemistry), Head Researcher, Laboratory of Polymer Science, Baikal Institute of Nature Management of the Siberian Branch of the RAS.

670047, Republic of Buryatia, Ulan-Ude, Sakhyanova str., 6.

Russian Federation

References

  1. Афиногенов Г.Е., Панарин Е.Ф. Антимикробные полимеры. СПб.: Гиппократ, 1993. 264 с.
  2. Воинцева И.И., Гембицкий П.А. Полигуанидины — дезинфекционные средства и полифункциональные добавки в композиционные материалы. М.: ЛКМ-пресс, 2009. 303 с.
  3. Крыжановская О.А., Лазарева А.В., Алябьева Н.М., Тепаев Р.Ф., Карасева О.В., Чеботарь И.В., Маянский Н.А. Устойчивость к антибиотикам и молекулярные механизмы резистентности у карбапенем-нечувствительных изолятов Klebsiella pneumoniae, выделенный в педиатрических ОРИТ г. Москвы // Антибиотики и химиотерапия. 2016. Т. 61, № 7–8. С. 22–26.
  4. Шкарин В.В., Саперкин Н.В., Ковалишена О.В., Благонравова А.С., Широкова И.Ю., Куликина А.А. Региональный мониторинг устойчивости микроорганизмов к дезинфектантам: итоги и перспективы // Медицинский альманах. 2012. Т. 3, № 22. С. 122–125.
  5. Яковлев С.В., Проценко Д.Н., Шахова Т.В., Суворова М.П., Рамишвили В.Ш., Игнатенко О.В., Ярошецкий А.И., Романовский Ю.Я., Еремина Л.В. Антибиотикорезистентность в стационаре: контролируем ли мы ситуацию? // Антибиотики и химиотерапия. 2010. Т. 55, № 1–2. С. 50–58.
  6. Albert M., Feiertag P., Hayn G. Structure-activity relationships of oligoguanidiness influence of counterion, diamine, and aver- age molecular weight on biocidal activities. Biomacromolecules, 2003, vol. 4, pp. 1811–1817. doi: 10.1021/bm0342180
  7. Stelmakh S.A., Grigor’eva M.N., Garkusheva N.M., Lebedeva S.N., Ochirov O.S., Mognonov D.M., Zhamsaranova S.D., Batoev V.B. Studies of new biocidal polyguanidines: antibacterial action and toxicity. Polymer Bulletin, 2020, vol. 78, pp. 1997– 2008. doi: 10.1007/s00289-020-03197-1

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Copyright (c) 2021 Ochirov O.S., Burasova E.G., Stelmakh S.A., Grigor'eva M.N., Okladnikova V.O., Mognonov D.M.

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