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The effect of drug dose and duration of adjuvant Amoxicillin-plus-Metronidazole to full-mouth scaling and root planing in periodontitis: a systematic review and meta-analysis

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Abstract

Objectives

The aim is to explore the optimal drug dose and duration of adjunctive Amoxicillin-plus-Metronidazole (AMX/MET) to full-mouth scaling and planing (FMSRP) in periodontitis.

Methods

An electronic search in four databases and manual search in four journals were conducted for randomised clinical trials comparing AMX/MET adjunct to FMSRP with FMSRP alone for at least 3 months.

Results

Eleven studies were eligible and included. The primary outcome was clinical attachment level (CAL) gain, the secondary outcomes were periodontal pocket depth (PPD) reduction and adverse events. Our results showed a beneficial effect of adjunctive AMX/MET with higher drug dose to FMSRP for CAL gain and PPD reduction at 3 months, and the benefit remained stable at 6 months. However, minimal difference among three-seven-and ten-day drug duration was observed. In addition, the risk difference of adverse events was minimal between two groups.

Conclusion

FMSRP adjunct to a high drug dose of 500/500 mg of AMX/MET showed a significant and stable improvement on 6-month follow-up period. No decision for drug duration could be made due to limited evidence.

Clinical relevance

On 6-month follow-up, higher dose of AMX/MET adjunct to FMSRP could provide a stable clinical effect. No recommendation for drug duration could be made.

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Change history

  • 20 March 2021

    The email of the author Li Zhao was corrected from lizhao2010@hospital.c0071mu.edu.cn to lizhao2010@hospital.cqmu.edu.cn.

References

  1. Goodson JM, Tanner A, McArdle S, Dix K, Watanabe SM (1991) Multicenter evaluation of tetracycline fiber therapy. III. Microbiological response. J Clin Periodontol 26:440–451. https://doi.org/10.1111/j.1600-0765.1991.tb01734.x

    Article  Google Scholar 

  2. Maiden MF, Tanner A, McArdle S, Najpauer K, Goodson JM (1991) Tetracycline fiber therapy monitored by DNA probe and cultural methods. J Clin Periodontol 26:452–459. https://doi.org/10.1111/j.1600-0765.1991.tb01735.x

    Article  Google Scholar 

  3. Harper DS, Robinson PJ (1987) Correlation of histometric, microbial, and clinical indicators of periodontal disease status before and after root planing. J Clin Periodontol 14:190–196. https://doi.org/10.1111/j.1600-051X.1987.tb00966.x

    Article  PubMed  Google Scholar 

  4. Petersilka GJ, Ehmke B, Flemmig TF (2002) Antimicrobial effects of mechanical debridement. Periodontol 28:56–71. https://doi.org/10.1034/j.1600-0757.2002.280103.x

    Article  Google Scholar 

  5. Quirynen M, Vogels R, Pauwels M, Haffajee AD, Socransky SS, Uzel NG, van Steenberghe D (2005) Initial subgingival colonization of “pristine” pockets. J Dent Res 84:340–344. https://doi.org/10.1177/154405910508400409

    Article  PubMed  Google Scholar 

  6. Sumida S, Ishihara K, Kishi M, Okuda K (2002) Transmission of periodontal disease-associated bacteria from teeth to osseointegrated implant regions. Int J Oral Maxillofac Implants 17:696–702

    PubMed  Google Scholar 

  7. Quirynen M, Bollen C, Vandekerckhove B, Dekeyser C, Papaioannou W, Eyssen H (1995) Full-vs. partial-mouth disinfection in the treatment of periodontal infections: short-term clinical and microbiological observations. J Dent Res 74:1459–1467. https://doi.org/10.1177/00220345950740080501

    Article  PubMed  Google Scholar 

  8. Lang NP, Tan WC, Krähenmann MA, Zwahlen M (2008) A systematic review of the effects of full-mouth debridement with and without antiseptics in patients with chronic periodontitis. J Clin Periodontol 35:8–21. https://doi.org/10.1111/cpe.2008.35.issue-s8

    Article  PubMed  Google Scholar 

  9. Eberhard J, Jepsen S, Jervøe-Storm PM, Needleman I, Worthington HV (2015) Full-mouth treatment modalities (within 24 hours) for chronic periodontitis in adults. Cochrane Database Syst Rev 17:CD004622. https://doi.org/10.1002/14651858.CD004622.pub3

    Article  Google Scholar 

  10. Fang H, Han M, Li QL, Cao CY, Xia R, Zhang ZH (2016) Comparison of full-mouth disinfection and quadrant-wise scaling in the treatment of adult chronic periodontitis: a systematic review and meta-analysis. J Periodontal Res 51:417–430. https://doi.org/10.1111/jre.12326

    Article  PubMed  Google Scholar 

  11. Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, Sculean A, Tonetti MS, EFP Workshop Participants and Methodological Consultants (2020) Treatment of stage I-III periodontitis—the EFP S3 level clinical practice guideline. J Clin Periodontol 47(Suppl 22):4–60. https://doi.org/10.1111/jcpe.13290

    Article  PubMed  PubMed Central  Google Scholar 

  12. Baltacioglu E, Aslan M, Saraç Ö, Saybak A, Yuva P (2011) Analysis of clinical results of systemic antimicrobials combined with nonsurgical periodontal treatment for generalized aggressive periodontitis: a pilot study. J Can Dent Assoc 77:b97

    PubMed  Google Scholar 

  13. Yashima A, Morozumi T, Yoshie H, Hokari T, Izumi Y, Akizuki T, Mizutani K, Takamatsu H, Minabe M, Miyauchi S, Yoshino T, Tanaka M, Tanaka Y, Gomi K (2019) Biological responses following one-stage full-mouth scaling and root planing with and without azithromycin: multicenter randomized trial. J Periodontal Res 54:709–719. https://doi.org/10.1111/jre.12680

    Article  PubMed  Google Scholar 

  14. Gomi K, Yashima A, Nagano T (2007) Effects of full-mouth scaling and root planing in conjunction with systemically administered azithromycin. J Periodontol 78:422–429

    Article  PubMed  Google Scholar 

  15. Del Peloso Ribeiro E, Bittencourt S, Zanin ICJ, Ambrosano GMB, Sallum EA, Nociti FH, Gonçalves RB, Casati MZ (2009) Full-mouth ultrasonic debridement associated with amoxicillin and metronidazole in the treatment of severe chronic periodontitis. J Periodontol 80:1254–1264. https://doi.org/10.1902/jop.2009.080403

    Article  Google Scholar 

  16. Cionca N, Giannopoulou C, Ugolotti G, Mombelli A (2009) Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis. J Periodontol 80:364–371. https://doi.org/10.1902/jop.2009.080540

    Article  PubMed  Google Scholar 

  17. Mombelli A, Cionca N, Almaghlouth A, Décaillet F, Courvoisier DS, Giannopoulou C (2013) Are there specific benefits of amoxicillin plus metronidazole in aggregatibacter actinomycetemcomitans-associated periodontitis? Double-masked, randomized clinical trial of efficacy and safety. J Periodontol 84:715–724. https://doi.org/10.1902/jop.2012.120281

    Article  PubMed  Google Scholar 

  18. Cosgarea R, Heumann C, Juncar R, Tristiu R, Lascu L, Salvi GE, Arweiler NB, Sculean A (2017) One year results of a randomized controlled clinical study evaluating the effects of non-surgical periodontal therapy of chronic periodontitis in conjunction with three or seven days systemic administration of amoxicillin/metronidazole. PLoS One 12:e0179592. https://doi.org/10.1371/journal.pone.0179592

    Article  PubMed  PubMed Central  Google Scholar 

  19. Cosgarea R, Juncar R, Heumann C, Tristiu R, Lascu L, Arweiler N, Stavropoulos A, Sculean A (2016) Non-surgical periodontal treatment in conjunction with 3 or 7 days systemic administration of amoxicillin and metronidazole in severe chronic periodontitis patients. A placebo-controlled randomized clinical study. J Clin Periodontol 43:767–777. https://doi.org/10.1111/jcpe.12559

    Article  PubMed  Google Scholar 

  20. Haffajee AD, Socransky SS, Gunsolley JC (2003) Systemic anti-infective periodontal therapy. A systematic review. Ann Periodontol 8:115–181. https://doi.org/10.1902/annals.2003.8.1.115

    Article  PubMed  Google Scholar 

  21. Herrera D, Sanz M, Jepsen S, Needleman I, Roldán S (2002) A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol 29:136–159. https://doi.org/10.1034/j.1600-051X.29.s3.8.x

    Article  PubMed  Google Scholar 

  22. Van Winkelhoff AJ, Tijhof CJ, De Graaff J (1992) Microbiological and clinical results of metronidazole plus amoxicillin therapy in Actinobacillus actinomycetemcomitans-associated periodontitis. J Periodontol 63:52–57. https://doi.org/10.1902/jop.1992.63.1.52

    Article  PubMed  Google Scholar 

  23. Zandbergen D, Slot DE, Niederman R, Van der Weijden FA (2016) The concomitant administration of systemic amoxicillin and metronidazole compared to scaling and root planing alone in treating periodontitis: a systematic review. BMC Oral Health 16:27. https://doi.org/10.1186/s12903-015-0123-6

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sgolastra F, Gatto R, Petrucci A, Monaco A (2012) Effectiveness of systemic amoxicillin/metronidazole as adjunctive therapy to scaling and root planing in the treatment of chronic periodontitis: a systematic review and meta-analysis. J Periodontol 83:1257–1269. https://doi.org/10.1902/jop.2012.110625

    Article  PubMed  Google Scholar 

  25. Teughels W, Feres M, Oud V, Martín C, Matesanz P, Herrera D (2020) Adjunctive effect of systemic antimicrobials in periodontitis therapy: a systematic review and meta-analysis. J Clin Periodontol 47(Suppl 22):257–281. https://doi.org/10.1111/jcpe.13264

    Article  PubMed  Google Scholar 

  26. Saleh A, Rincon J, Tan A, Firth M (2016) Comparison of adjunctive azithromycin and amoxicillin/metronidazole for patients with chronic periodontitis: preliminary randomized control trial. Aust Dent J 61:469–481. https://doi.org/10.1111/adj.12415

    Article  PubMed  Google Scholar 

  27. Liaw A, Miller C, Nimmo A (2019) Comparing the periodontal tissue response to non-surgical scaling and root planing alone, adjunctive azithromycin, or adjunctive amoxicillin plus metronidazole in generalized chronic moderate-to-severe periodontitis: a preliminary randomized controlled trial. Aust Dent J 64:145–152. https://doi.org/10.1111/adj.12674

    Article  PubMed  Google Scholar 

  28. Keestra JAJ, Grosjean I, Coucke W, Quirynen M, Teughels W (2015) Non-surgical periodontal therapy with systemic antibiotics in patients with untreated chronic periodontitis: a systematic review and meta-analysis. J Periodontol 50:294–314. https://doi.org/10.1111/jre.2015.50.issue-3

    Article  Google Scholar 

  29. McGowan K, McGowan T, Ivanovski S (2018) Optimal dose and duration of amoxicillin-plus-metronidazole as an adjunct to non-surgical periodontal therapy: a systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Periodontol 45:56–67. https://doi.org/10.1111/jcpe.12830

    Article  PubMed  Google Scholar 

  30. Slama TG, Amin A, Brunton SA, File TM Jr, Milkovich G, Rodvold KA, Sahm DF, Varon J, Weiland D Jr (2005) A clinician’s guide to the appropriate and accurate use of antibiotics: the Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria. Am J Med 118(Suppl 7A):1S–6S. https://doi.org/10.1016/j.amjmed.2005.05.007

    Article  PubMed  Google Scholar 

  31. Higgins JPT, Altman D, Sterne J (2011) Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (ed) Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). The Cochrane Collaboration: Copenhagen, pp 187–241.

  32. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  33. Boia S, Boariu M, Baderca F, Rusu D, Muntean D, Horhat F, Boia ER, Borza C, Anghel A, Stratul ŞI (2019) Clinical, microbiological and oxidative stress evaluation of periodontitis patients treated with two regimens of systemic antibiotics, adjunctive to non-surgical therapy. A placebo-controlled randomized clinical trial. Exp Ther Med 18:5001–5015. https://doi.org/10.3892/etm.2019.7856

    Article  PubMed  PubMed Central  Google Scholar 

  34. Casarin RCV, Del Peloso Ribeiro E, Sallum EA, Nociti FH Jr, Gonçalves RB, Casati MZ (2012) The combination of amoxicillin and metronidazole improves clinical and microbiologic results of one-stage, full-mouth, ultrasonic debridement in aggressive periodontitis treatment. J Periodontol 83:988–998. https://doi.org/10.1902/jop.2012.110513

    Article  PubMed  Google Scholar 

  35. Aimetti M, Romano F, Guzzi N, Carnevale G (2012) Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial. J Clin Periodontol 39:284–294. https://doi.org/10.1111/j.1600-051X.2011.01795.x

    Article  PubMed  Google Scholar 

  36. Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, Tonetti MS (2005) Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol 32:1096–1107. https://doi.org/10.1111/j.1600-051X.2005.00814.x

    Article  PubMed  Google Scholar 

  37. Varela VM, Heller D, Silva-Senem MX, Torres MC, Colombo AP, Feres-Filho EJ (2011) Systemic antimicrobials adjunctive to a repeated mechanical and antiseptic therapy for aggressive periodontitis: a 6-month randomized controlled trial. J Periodontol 82:1121–1130. https://doi.org/10.1902/jop.2011.100656

    Article  PubMed  Google Scholar 

  38. Almaghlouth AA, Cionca N, Cancela JA, Décaillet F, Courvoisier DS, Giannopoulou C, Mombelli A (2014) Effect of periodontal treatment on peak serum levels of inflammatory markers. Clin Oral Investig 18:2113–2121. https://doi.org/10.1007/s00784-014-1187-4

    Article  PubMed  Google Scholar 

  39. Harks I, Koch R, Eickholz P, Hoffmann T, Kim TS, Kocher T, Meyle J, Kaner D, Schlagenhauf U, Doering S, Holtfreter B, Gravemeier M, Harmsen D, Ehmke B (2015) Is progression of periodontitis relevantly influenced by systemic antibiotics? A clinical randomized trial. J Clin Periodontol 42:832–842. https://doi.org/10.1111/jcpe.12441

    Article  PubMed  PubMed Central  Google Scholar 

  40. Caton JG, Armitage G, Berglundh T, Chapple ILC, Jepsen S, Kornman KS, Mealey BL, Papapanou PN, Sanz M, Tonetti MS (2018) A new classification scheme for periodontal and peri-implant diseases and conditions. Periodontology 45(Suppl 20):S1–S8. https://doi.org/10.1111/jcpe.12935

    Article  Google Scholar 

  41. Rooney J, Wade W, Sprague SV, Newcombe RG, Addy M (2002) Adjunctive effects to non-surgical periodontal therapy of systemic metronidazole and amoxycillin alone and combined. J Clin Periodontol 29:342–350. https://doi.org/10.1034/j.1600-051X.2002.290410.x

    Article  PubMed  Google Scholar 

  42. Feres M, Soares GMS, Mendes JAV, Silva MP, Faveri M, Teles R, Socransky SS, Figueiredo LC (2012) Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo controlled, randomized clinical trial. J Clin Periodontol 39:1149–1158. https://doi.org/10.1111/jcpe12004

    Article  PubMed  Google Scholar 

  43. Taiete T, Casati MZ, Del Peloso Ribeiro E, Sallum EA, Nociti FH Jr, Casarin RC (2016) Amoxicillin/metronidazole associated with nonsurgical therapy did not promote additional benefits in immunologic parameters in generalized aggressive periodontitis: a randomized controlled clinical trial. Quintessence Int 47:281–292. https://doi.org/10.3290/j.qi.a34723

    Article  PubMed  Google Scholar 

  44. Borges I, Faveri M, Figueiredo LC, Duarte PM, Retamal-Valdes B, Montenegro SCL, Feres M (2017) Different antibiotic protocols in the treatment of severe chronic periodontitis: a 1-year randomized trial. J Clin Periodontol 44:822–832. https://doi.org/10.1111/jcpe.2017.44.issue-8

    Article  PubMed  Google Scholar 

  45. Boia S, Stratul ŞI, Boariu M, Ursoniu S, Goţia SL, Boia ER, Borza C (2018) Evaluation of antioxidant capacity and clinical assessment of patients with chronic periodontitis treated with non-surgical periodontal therapy and adjunctive systemic antibiotherapy. Romanian J Morphol Embryol 59:1107–1113

    Google Scholar 

  46. Feres M, Haffajee AD, Allard K, Som S, Goodson JM, Socransky SS (2002) Antibiotic resistance of subgingival species during and after antibiotic therapy. J Clin Periodontol 29:724–735. https://doi.org/10.1034/j.1600-051X.2002.290809.x

    Article  PubMed  Google Scholar 

  47. Smiley CJ, Tracy SL, Abt E, Michalowicz BS, John MT, Gunsolley J, Cobb CM, Rossmann J, Harrel SK, Forrest JL, Hujoel PP, Noraian KW, Greenwell H, Frantsve-Hawley J, Estrich C, Hanson N (2015) Systematic review and meta-analysis on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. J Am Dent Assoc 146:508–524. https://doi.org/10.1016/j.adaj.2015.01.028

    Article  PubMed  Google Scholar 

  48. Pechère JC, Hughes D, Kardas P, Cornaglia G (2007) Non-compliance with antibiotic therapy for acute community infections: a global survey. Int J Antimicrob Agents 29:245–253. https://doi.org/10.1016/j.ijantimicag.2006.09.026

    Article  PubMed  Google Scholar 

  49. Winkel EG, Van Winkelhoff AJ, Timmerman MF, Van der Velden U, Van der Weijden GA (2001) Amoxicillin plus metronidazole in the treatment of adult periodontitis patients. A double-blind placebo-controlled study. J Clin Periodontol 28:296–305. https://doi.org/10.1034/j.1600-051x.2001.028004296.x

    Article  PubMed  Google Scholar 

  50. Ehmke B, Moter A, Beikler T, Milian E, Flemmig TF (2005) Adjunctive antimicrobial therapy of periodontitis: long-term effects on disease progression and oral colonization. J Clin Periodontol 76:749–759. https://doi.org/10.1902/jop.2005.76.5.749

    Article  Google Scholar 

  51. Silva MP, Feres M, Sirotto TA, Soares GM, Mendes JA, Faveri M, Figueiredo LC (2011) Clinical and microbiological benefits of metronidazole alone or with amoxicillin as adjuncts in the treatment of chronic periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol 38:828–837. https://doi.org/10.1111/j.1600-051X.2011.01763.x

    Article  PubMed  Google Scholar 

  52. Santos CM, Lira-Junior R, Fischer RG, Santos AP, Oliveira BH (2015) Systemic antibiotics in periodontal treatment of diabetic patients: a systematic review. PLoS One 10:e0145262. https://doi.org/10.1371/journal.pone.0145262

    Article  PubMed  PubMed Central  Google Scholar 

  53. Angaji M, Gelskey S, Nogueira-Filho G, Brothwell D (2010) A systematic review of clinical efficacy of adjunctive antibiotics in the treatment of smokers with periodontitis. J Periodontal 81:1518–1528. https://doi.org/10.1902/jop.2010.100192

    Article  Google Scholar 

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Funding

Author Han Zhao was funded by the Beijing Stomatological Hospital, School of Stomatology, Capital Medical University for research in University Witten/Herdecke.

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Authors and Affiliations

  1. Multi-disciplinary Treatment Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tian Tan Xi Li Number.4, Beijing, 100050, China

    Han Zhao

  2. Department of Periodontology, Witten/Herdecke University, Alfred-Herrhausen-Str. 45, 58445, Witten, Germany

    Han Zhao & Jingchao Hu

  3. Department of Periodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Tian Tan Xi Li Number 4, Beijing, 100050, China

    Jingchao Hu

  4. Department of Prosthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 400015, China

    Li Zhao

  5. Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 400015, China

    Li Zhao

  6. Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 400015, China

    Li Zhao

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Contributions

H. Zhao contributed to study conceptualization and design, acquisition of data, data collection and original draft preparation; JC. Hu contributed to study conceptualization, data collection, and critically revised the manuscript; L. Zhao contributed to study design, software, statistical analyses and interpretation of data. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Li Zhao.

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Author Han Zhao declares that he has no conflict of interest. Author Jingchao Hu declares that he has no conflict of interest. Author Li Zhao declares that he has no conflict of interest.

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Zhao, H., Hu, J. & Zhao, L. The effect of drug dose and duration of adjuvant Amoxicillin-plus-Metronidazole to full-mouth scaling and root planing in periodontitis: a systematic review and meta-analysis. Clin Oral Invest 25, 5671–5685 (2021). https://doi.org/10.1007/s00784-021-03869-w

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