Сравнительный анализ эффективности хлоргексидинсодержащих антисептических препаратов, применяемых в пародонтологии и имплантологии

Актуальность. Несмотря на разнообразие лекарственных средств с антибактериальным эффектом, в том числе многокомпонентных, золотым стандартом антисептических препаратов, актуальных в терапии заболеваний пародонта, в настоящее время являются хлоргексидинсодержащие. В то же время нежелательные побочные эффекты, новые данные о неблагоприятном воздействии от применения хлоргексидина на микробиом определяют необходимость поиска оптимального хлоргексидинсодержащего продукта, сочетающего высокую эффективность и относительную безвредность. Цель исследования: провести сравнительный анализ эффективности хлоргексидинсодержащих антисептических препаратов, применяемых в стоматологической практике.

Материалы и методы. Были проанализированы результаты клинических исследований, посвященных изучению эффективности хлоргексидина в терапии заболеваний пародонта, опубликованные в период с 2018 по 2023 год. Подбор публикаций производили в базе данных PubMed по ключевым словам: chlorhexidine, periodontal disease, periodontitis. Общее количество публикаций, отвечающих критериям поиска, составило 84. В результате первичного анализа всех доступных публикаций, согласно критериям включения и не включения было изучено и проанализировано 27 публикации.

Результаты. В результате анализа данных клинических исследований, проведенных за последние пять лет, было установлено, что в медикаментозном сопровождении терапии заболеваний пародонта обнаруживается тенденция к более частому применению более высоких концентраций препаратов хлоргексидина, таких как 0,12% и 0,2%.

Заключение. Факт назначения хлоргексидинсодержащих препаратов должен быть обоснованным и отвечать особенностям клинической картины. При этом подбор концентрации действующего вещества хлоргексидина, форма выпуска лекарственного препарата, длительность применения должны быть тщательно подобраны в соответствии с клинической ситуацией и преследуемой целью.

1. Sedghi L, DiMassa V, Harrington A, Lynch SV, Kapila YL. The oral microbiome: Role of key organisms and complex networks in oral health and disease. Periodontol 2000. 2021;87(1):107-131. doi: 10.1111/prd.12393

2. Joseph S, Curtis MA. Microbial transitions from health to disease. Periodontol 2000. 2021;86(1):201-209. doi: 10.1111/prd.12377

3. Figuero E, Roldán S, Serrano J, Escribano M, Martín C, Preshaw PM. Efficacy of adjunctive therapies in patients with gingival inflammation: A systematic review and meta-analysis. J Clin Periodontol. 2020;47 Suppl 22:125-143. doi: 10.1111/jcpe.13244

4. Jones CG. Chlorhexidine: is it still the gold standard? Periodontol 2000. 1997;15:55-62. doi: 10.1111/j.1600-0757.1997.tb00105.x)

5. Poppolo Deus F, Ouanounou A. Chlorhexidine in Dentistry: Pharmacology, Uses, and Adverse Effects. Int Dent J. 2022;72(3):269-277. doi: 10.1016/j.identj.2022.01.005)

6. Stuar MVt, Kouimtz M, Hill SR, editors. WHO model formulary 2008. World Health Organization. 2009. Available from: https://iris.who.int/handle/10665/44053

7. National Center for Biotechnology Information. PubChem Compound Summary for CID 9552081, Chlorhexidine Gluconate. PubChem. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Chlorhexidine-Gluconate

8. Richards A. Oral Hygiene Products. In: Schmalz G, Arenholt-Bindslev D, editors. Biocompatibility of Dental Materials. Berlin, Heidelberg: Springer;2009. pp.271-292. doi: 10.1007/978-3-540-77782-3_10

9. World Health Organization model list of essential medicines: 21st list. World Health Organization. 2019. Available from: https://iris.who.int/handle/10665/325771.

10. World Health Organization model list of essential medicines: 22nd list. World Health Organization. 2021. Available from: https://iris.who.int/handle/10665/345533

11. Wade RG, Burr NE, McCauley G, Bourke G, Efthimiou O. The Comparative Efficacy of Chlorhexidine Gluconate and Povidone-iodine Antiseptics for the Prevention of Infection in Clean Surgery: A Systematic Review and Network Meta-analysis. Ann Surg. 2021;274(6):e481-e488. doi: 10.1097/SLA.0000000000004076

12. Dumville JC, McFarlane E, Edwards P, Lipp A, Holmes A, Liu Z. Preoperative skin antiseptics for preventing surgical wound infections after clean surgery. Cochrane Database Syst Rev. 2015;2015(4):CD003949. doi: 10.1002/14651858.CD003949.pub4

13. Sanz M, Herrera D, Kebschull M, et al. Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline [published correction appears in J Clin Periodontol. 2021 Jan;48(1):163]. J Clin Periodontol. 2020;47 Suppl 22(Suppl 22):4-60. doi: 10.1111/jcpe.13290.

14. Ricard JD, Lisboa T. Caution for chlorhexidine gluconate use for oral care: insufficient data. Intensive Care Med. 2018;44(7):1162-1164. doi: 10.1007/s00134-018-5217-6

15. Stuart MC, Kouimtzi M, Hill SR, editors. WHO model formulary 2008. World Health Organization. 2008:321-322. Available from: https://iris.who.int/handle/10665/44053

16. Bailey A, Longson M. Virucidal activity of chlorhexidine on strains of Herpesvirus hominis, poliovirus, and adenovirus. J Clin Pathol. 1972;25(1):76-8. doi: 10.1136/jcp.25.1.76.

17. Brookes ZLS, Bescos R, Belfield LA, Ali K, Roberts A. Current uses of chlorhexidine for management of oral disease: a narrative review. J Dent. 2020;103:103497. doi: 10.1016/j.jdent.2020.103497)

18. Leikin JB, Paloucek FP. Chlorhexidine Gluconate. In: Leikin JB, Paloucek FP, edotors. Poisoning and Toxicology Handbook (4th ed.). Informa. 2008 pp. 183–84. Available from: https://www.researchgate.net/publication/285900926_Poisoning_and_toxicology_handbook

19. Machtei EE, Romanos G, Kang P, Travan S, Schmidt S, Papathanasiou E, et al. Repeated delivery of chlorhexidine chips for the treatment of peri-implantitis: A multicenter, randomized, comparative clinical trial. J. Periodontol. 2021;92(1):11-20. doi: 10.1002/JPER.20-0353

20. James P, Worthington HV, Parnell C, et al. Chlorhexidine mouthrinse as an adjunctive treatment for gingival health. Cochrane Database Syst Rev. 2017;3(3):CD008676. doi: 10.1002/14651858.CD008676.pub2

21. Bernardi F, Pincelli MR, Carloni S, Gatto MR, Montebugnoli L. Chlorhexidine with an Anti Discoloration System. A comparative study. Int J Dent Hyg. 2004;2(3):122-126. doi: 10.1111/j.1601-5037.2004.00083.x

22. Sanz M, Vallcorba N, Fabregues S, Müller I, Herkströter F. The effect of a dentifrice containing chlorhexidine and zinc on plaque, gingivitis, calculus and tooth staining. J Clin Periodontol. 1994;21(6):431-437. doi: 10.1111/j.1600-051x.1994.tb00741.x

23. Kumar S, Patel S, Tadakamadla J, Tibdewal H, Duraiswamy P, Kulkarni S. Effectiveness of a mouthrinse containing active ingredients in addition to chlorhexidine and triclosan compared with chlorhexidine and triclosan rinses on plaque, gingivitis, supragingival calculus and extrinsic staining. Int J Dent Hyg. 2013;11(1):35-40. doi: 10.1111/j.1601-5037.2012.00560.x

24. Tambur ZZ, Aleksić ED, Čabrilo Lazić MP, et al. The investigation of antibacterial activity of hyperlight fluid fusion subcellular essential complex. J Infect Dev Ctries. 2023;17(5):643-648. doi: 10.3855/jidc.17740

25. Nayak N, Varghese J, Shetty S, Bhat V, Durgekar T, Lobo R, Nayak UY, et al. Evaluation of a mouthrinse containing guava leaf extract as part of comprehensive oral care regimen- a randomized placebo-controlled clinical trial. BMC Complement Altern Med. 2019;19(1):327. doi: 10.1186/s12906-019-2745-8

26. De Waal YCM, Vangsted TE, Van Winkelhoff AJ. Systemic antibiotic therapy as an adjunct to non-surgical peri-implantitis treatment: A single-blind RCT. J Clin Periodontol. 2021;48(7):996-1006. doi: 10.1111/jcpe.13464

27. Bollain J, Pulcini A, Sanz-Sánchez I, Figuero E, Alonso B, Sanz M, et al. Efficacy of a 0.03% chlorhexidine and 0.05% cetylpyridinium chloride mouth rinse in reducing inflammation around the teeth and implants: a randomized clinical trial. Clin Oral Investig. 2021;25(4):1729-1741. doi: 10.1007/s00784-020-03474-3

28. Melo de Menezes K, Roncalli da Costa Oliveira ÂG, de Vasconcelos Gurgel BC. Impact of 0.12% Chlorhexidine Gluconate Mouthwash on Peri-Implant Mucositis and Gingivitis After Nonsurgical Treatment: A Multilevel Analysis. Int J Oral Maxillofac Implants. 2021;36(6):1188-1197. doi: 10.11607/jomi.8994

29. Alqutub MN, Alhumaidan AA, Alali Y, Al-Aali KA, Javed F, Vohra F, Abduljabbar T. Comparison of the postoperative anti-inflammatory efficacy of chlorhexidine, saline rinses and herbal mouthwashes after mechanical debridement in patients with peri-implant mucositis: A randomized controlled trial. Int J Dent Hyg. 2023;21(1):203-210. doi: 10.1111/idh.12582.

30. Cosola S, Oldoini G, Giammarinaro E, Covani U, Genovesi A, Marconcini S. The effectiveness of the information-motivation model and domestic brushing with a hypochlorite-based formula on peri-implant mucositis: A randomized clinical study. Clin Exp Dent Res. 2022;8(1):350-358. doi: 10.1002/cre2.487

31. Bunk D, Eisenburger M, Häckl S, Eberhard J, Stiesch M, Grischke J. The effect of adjuvant oral irrigation on self-administered oral care in the management of peri-implant mucositis: A randomized controlled clinical trial. Clin Oral Implants Res. 2020;31(10):946-958. doi: 10.1111/clr.13638.

32. Philip J, Laine ML, Wismeijer D. Adjunctive effect of mouthrinse on treatment of peri-implant mucositis using mechanical debridement: A randomized clinical trial. J Clin Periodontol. 2020;47(7):883-891. doi: 10.1111/jcpe.13295

33. Pena M, Barallat L, Vilarrasa J, Vicario M, Violant D, Nart J. Evaluation of the effect of probiotics in the treatment of peri-implant mucositis: a tripleblind randomized clinical trial. Clin Oral Investig. 2019;23(4):1673-1683. doi: 10.1007/s00784-018-2578-8

34. Collins JR, Veras K, Hernández M, Hou W, Hong H, Romanos GE. Anti-inflammatory effect of salt water a поnd chlorhexidine 0.12% mouthrinse after periodontal surgery: a randomized prospective clinical study. Clin Oral Investig. 202;25(7):4349-4357. doi: 10.1007/s00784-020-03748-w

35. Mauland EK, Preus HR, Aass AM. Comparison of commercially available 0.2% chlorhexidine mouthwash with and without anti-discoloration system: A blinded, crossover clinical trial. J Clin Periodontol. 2020;47(12):1522-1527. doi: 10.1111/jcpe.13382

36. Trombelli L, Simonelli A, Pramstraller M, Guarnelli ME, Fabbri C, Maietti E, Farina R. Clinical efficacy of a chlorhexidine-based mouthrinse containing hyaluronic acid and an antidiscoloration system in patients undergoing flap surgery: A triple-blind, parallel-arm, randomized controlled trial. Int J Dent Hyg. 2018;16(4):541-552. doi: 10.1111/idh.12361

37. Al-Mahmood S, Sabea DW. Comparative Evaluation of the Effectiveness of 40% Miswak Mouthwash and 0.12% Chlorhexidine Mouthwash in Treating Gingivitis: A Blinded, Randomised Clinical Trial. Oral Health Prev Dent. 2021;19(1):229-233. doi:10.3290/j.ohpd.b1179501

38. Al-Zawawi AS, Shaheen MY, Divakar DD, Aldulaijan HA, Basudan AM. Postoperative anti-inflammatory efficacy of 2% saline rinses and a herbal- mouthwash after non-surgical periodontal therapy for the management of periodontal inflammation in young adults with chlorhexidine allergy: A randomized controlled trial. Int J Dent Hyg. 2022;20(2):408-414 doi:10.1111/idh.12583

39. Vitt A, Gustafsson A, Ramberg P, Slizen V, Kazeko LA, Buhlin K. Polyhexamethylene guanidine phosphate irrigation as an adjunctive to scaling and root planing in the treatment of chronic periodontitis. Acta Odontol Scand. 2019;77(4):290-295. doi: 10.1080/00016357.2018.1541099

40. Mummolo S, Severino M, Campanella V, Barlattani A Jr, Quinzi V, Marchetti E. Chlorhexidine gel used as antiseptic in periodontal pockets. J Biol Regul Homeost Agents. 2019;33(3 Suppl. 1):83-88. Available from: https://pubmed.ncbi.nlm.nih.gov/31538453/

41. Hatila S, Lahiri B, Sunnanguli G, et al. Comparative Assessment of the Effect of Three Various Local Drug Delivery Medicaments in the Management of Chronic Periodontitis. J Contemp Dent Pract. 2023;24(3):162-167. doi:10.5005/jp-journals-10024-3455

42. Hasan F, Ikram R, Adel A, Abbas A, Ain Bukhari QU, Asadullah K. Treatment of periodontal diseases by the local drug delivery system using 1% chlorhexidine gel: A randomized clinical trial. Pak J Pharm Sci. 2021;34(1):41-45. Available from: https://pubmed.ncbi.nlm.nih.gov/34248001/

43. Marconcini S, Goulding M, Oldoini G, Attanasio C, Giammarinaro E, Genovesi A. Clinical and patient-centered outcomes post non-surgical periodontal therapy with the use of a non-injectable anesthetic product: A randomized clinical study. J Investig Clin Dent. 2019;10(4):e12446 doi:10.1111/jicd.12446

44. Afacan B, Çınarcık S, Gürkan A, Ozdemir G, Ilhan HA, Vurval C, et al. Full-mouth disinfection effects on gingival fluid calprotectin, osteocalcin, and N-telopeptide of Type I collagen in severe periodontitis. J Periodontol. 2020;91(5):638-650. doi: 10.1002/JPER.19-0445

45. Manau-Navarro C, Guasch-Serra S. Métodos de control de placa bacteriana. In: Cuenca E, Manau C, Serra LL, editors. Odontología Preventiva y Comunitaria. Principios Métodos y Aplicaciones. Barcelona: Masson; 2003:69-88. Available from: https://books.google.ru/books/about/Odontologia_Preventiva_y_Comunitaria_Pri.html?id=6xc0PQAACAAJ&redir_esc=y

46. Van Strydonck DA, Timmerman MF, Van der Velden U, Van der Weijden GA. Chlorhexidine mouthrinse in combination with an SLS-containing dentifrice and a dentifrice slurry. J Clin Periodontol. 2006;33(5):340-344. doi: 10.1111/j.1600-051X.2006.00910.x

47. Elkerbout TA, Slot DE, Bakker EW, Van der Weijden GA. Chlorhexidine mouthwash and sodium lauryl sulphate dentifrice: do they mix effectively or interfere? Int J Dent Hyg. 2016;14(1):42-52. doi: 10.1111/idh.12125

48. Barkvoll P, Rølla G, Svendsen K. Interaction between chlorhexidine digluconate and sodium lauryl sulfate in vivo. J Clin Periodontol. 1989;16(9):593-595. doi: 10.1111/j.1600-051x.1989.tb02143.x

49. Kolahi J, Soolari A. Rinsing with chlorhexidine gluconate solution after brushing and flossing teeth: a systematic review of effectiveness. Quintessence Int. 2006;37(8):605-612. Available from: https://www.quintessence-publishing.com/deu/en/article/839700

50. Xiang H, Zuo J, Guo F, Dong D. What we already know about rhubarb: a comprehensive review. Chin Med. 2020;15:88 doi: 10.1186/s13020-020-00370-6

51. Olorunnipa TA, Igbokwe CC, Lawal TO, Adeniyi BA, Mahady GB. Anti-helicobacter pylori activity of Abelmoschus esculentus L. moench (okra): An in vitro study. Afr J Pure Appl Chem. 2013;(7):330-336 doi: 10.4172/2327-5073.1000132

52. Agarwal SK, Singh SS, Verma S, Kumar S. Antifungal activity of anthraquinone derivatives from Rheum emodi. J Ethnopharmacol. 2000;72(1-2):43-46. doi: 10.1016/s0378-8741(00)00195-1

53. Malik MA, Bhat SA, Fatima B, Ahmad SB, Sidiqui S, Shrivastava R. Rheum emodi as a valuable medicinal plant. Int J Gen Med Pharm. 2016;5(4):35-44. Available from: https://www.researchgate.net/publication/305067732_RHEUM_EMODI_AS_VALUABLE_MEDICINAL_PLANT

54. Lu C, Wang H, Lv W, Xu P, Zhu J, Xie J, et al. Antibacterial properties of anthraquinones extracted from rhubarb against Aeromonas hydrophila. Fish Sci. 2011;77:375. Available from: https://link.springer.com/article/10.1007/s12562-011-0341-z

55. Liao J, Zhao L, Yoshioka M, Hinode D, Grenier D. Effects of Japanese traditional herbal medicines (Kampo) on growth and virulence properties of Porphyromonas gingivalis and viability of oral epithelial cells. Pharm Biol. 2013;51(12):1538-1544. doi: 10.3109/13880209.2013.801995

56. Kulik EM, Waltimo T, Weiger R, et al. Development of resistance of mutans streptococci and Porphyromonas gingivalis to chlorhexidine digluconate and amine fluoride/stannous fluoride-containing mouthrinses, in vitro. Clin Oral Investig. 2015;19(6):1547-1553. doi: 10.1007/s00784-014-1379-y doi: 10.1016/j.jpha.2019.11.002

57. Humphries R, Bobenchik AM, Hindler JA, Schuetz AN. Overview of Changes to the Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing, M100, 31st Edition. J Clin Microbiol. 2021;59(12):e0021321. doi: 10.1128/JCM.00213-21

58. Müller-Heupt LK, Vierengel N, Groß J, Opatz T, Deschner J, von Loewenich FD. Antimicrobial Activity of Eucalyptus globulus, Azadirachta indica, Glycyrrhiza glabra, Rheum palmatum Extracts and Rhein against Porphyromonas gingivalis. Antibiotics (Basel). 2022;11(2):186. doi: 10.3390/antibiotics11020186

59. Zhang Q, Liu J, Li R, Zhao R, Zhang M, Wei S, et al. A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. against Lung Cancer via Induction of Apoptosis. Front. Pharmacol. 2020;11:528308. doi: 10.3389/fphar.2020.528308

60. Seukep AJ, Kuete V, Nahar L, Sarker SD, Guo M. Plant-derived secondary metabolites as the main source of efflux pump inhibitors and methods for identification. J. Pharm. Anal. 2020;10(4): 277–290. doi: 10.1016/j.jpha.2019.11.002

61. Ingendoh-Tsakmakidis A, Eberhard J, Falk CS, Stiesch M, Winkel A. In Vitro Effects of Streptococcus oralis Biofilm on Peri-Implant Soft Tissue Cells. Cells. 2020;9(5):1226. doi: 10.3390/cells9051226

62. Rubright WC, Walker JA, Karlsson UL, Diehl DL. Oral slough caused by dentifrice detergents and aggravated by drugs with antisialic activity. J Am Dent Assoc. 1978;97(2):215-220. doi: 10.14219/jada.archive.1978.0260

63. Shim YJ, Choi JH, Ahn HJ, Kwon JS. Effect of sodium lauryl sulfate on recurrent aphthous stomatitis: a randomized controlled clinical trial. Oral Dis. 2012;18(7):655-660. doi: 10.1111/j.1601-0825.2012.01920.x

64. Ahlfors EE, Lyberg T. Contact sensitivity reactions in the oral mucosa. Acta Odontol Scand. 2001;59(4):248-254. doi: 10.1080/00016350152509283