Advertisement

Should Antibiotics Be Rationed in Periodontics—if Yes, how?

  • Andrea MombelliEmail author
Clinical Periodontics (Y Stathopoulou, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Clinical Periodontics

Abstract

Purpose

Based on the latest findings, we evaluate the benefits and risks of systemic antibiotics in periodontal treatment and search for opportunities to reduce their use.

Recent Findings

Thorough mechanical debridement by deep scaling and root planing (SRP) resolves a considerable amount of pathology on its own. Thus, antibiotics are not needed for most cases of periodontitis. Specific indications are the presence of multiple deep pockets, especially in the molar area and rapid rate of progression. There, SRP plus amoxicillin-metronidazole can be an efficacious, minimally invasive, rapid, and inexpensive form of treatment. Considering recent findings on benefits and unwanted effects of antibiotics, we present three scenarios to limit or optimize their use.

Summary

Antibiotics are no alternative for high-quality SRP or oral hygiene. Antibiotics adjunctive to SRP should be weighed on an individual basis against the necessity of further therapy at a later stage.

Keywords

Antibiotics Periodontal therapy Rationing Decision-making 

Notes

Acknowledgements

The author expresses his gratitude to Doctor Stefan Harbarth, Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, Switzerland, for reviewing the manuscript and helpful suggestions. Dr. Philipp Wick treated the case depicted in Fig. 1 during his postgraduate training at the University of Geneva School of Dental Medicine.

Funding Information

The author’s work on antimicrobial therapy as adjunct to periodontal treatment was supported by the Swiss National Science Foundation, Grant No. 320030-122089.

Compliance with Ethical Standards

Conflict of Interest

Dr. Mombelli reports a grant from Swiss National Science Foundation and non-financial support from Institute for Applied Immunology during the conduct of the study.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Dowd B, Allison K. Improving the rhetoric of rationing: part 1. Health Affairs Blog, June 24, 2013. 2013: https://www.healthaffairs.org/do/10.1377/hblog20130624.032272/full/. Date accessed: July 8, 2019.
  2. 2.
    Center for Disease Dynamics Economics & Policy. ResistanceMap: Antibiotic use 2018. 2018: https://resistancemap.cddep.org/AntibioticUse.php. Date accessed: May 31, 2018.
  3. 3.
    European Medicines Agency. Sales of veterinary antimicrobial agents in 30 European countries in 2015. European surveillance of veterinary antimicrobial consumption 2017;EMA/184855/2017.:www.ema.europa.eu/docs/en_GB/document_library/Report/2017/.../WC500236750.pdf. Date accessed June 13, 2018.
  4. 4.
    Federal Office of Public Health and Federal Food Safety and Veterinary Office. Swiss Antibiotic Resistance Report 2018. Usage of antibiotics and occurrence of antibiotic resistance in bacteria from humans and animals in Switzerland. Bern; 2018. FOPH publication number: 2018-OEG-87.Google Scholar
  5. 5.
    Bodenmann P, Vaucher P, Wolff H, Favrat B, de Tribolet F, Masserey E, et al. Screening for latent tuberculosis infection among undocumented immigrants in Swiss healthcare centres; a descriptive exploratory study. BMC Infect Dis. 2009;9:34.Google Scholar
  6. 6.
    Wettstein Rosenkranz K, Rothenanger E, Brodard I, Collaud A, Overesch G, Bigler B, et al. Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) among Swiss veterinary health care providers: detection of livestock- and healthcare-associated clones. Schweiz Arch Tierheilkd. 2014;156(7):317–25.Google Scholar
  7. 7.
    European Centre for Disease Prevention and Control. Multidrug-resistant tuberculosis in migrants, multi-country cluster – 2017. Stockholm: ECDC; 2017.Google Scholar
  8. 8.
    Auer C, Kiefer S, Zuske M, Schindler C, Wyss K, Blum J, et al. Health-seeking behaviour and treatment delay in patients with pulmonary tuberculosis in Switzerland: some slip through the net. Swiss Med Wkly. 2018;148:w14659.Google Scholar
  9. 9.
    Bronzwaer SL, Cars O, Buchholz U, Molstad S, Goettsch W, Veldhuijzen IK, et al. A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerg Infect Dis. 2002;8(3):278–82.Google Scholar
  10. 10.
    Goossens H, Ferech M, Vander Stichele R, Elseviers M, Group EP. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005;365(9459):579–87.CrossRefGoogle Scholar
  11. 11.
    Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, et al. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci U S A. 2015;112(18):5649–54.CrossRefGoogle Scholar
  12. 12.
    Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology. 2010;156(Pt 11):3216–23.CrossRefGoogle Scholar
  13. 13.
    Jakobsson HE, Jernberg C, Andersson AF, Sjolund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One. 2010;5(3):e9836.CrossRefGoogle Scholar
  14. 14.
    Perez-Cobas AE, Artacho A, Knecht H, Ferrus ML, Friedrichs A, Ott SJ, et al. Differential effects of antibiotic therapy on the structure and function of human gut microbiota. PLoS One. 2013;8(11):e80201.CrossRefGoogle Scholar
  15. 15.
    Perez-Cobas AE, Gosalbes MJ, Friedrichs A, Knecht H, Artacho A, Eismann K, et al. Gut microbiota disturbance during antibiotic therapy: a multi-omic approach. Gut. 2013;62(11):1591–601.CrossRefGoogle Scholar
  16. 16.
    Stewardson AJ, Huttner B, Harbarth S. At least it won't hurt: the personal risks of antibiotic exposure. Curr Opin Pharmacol. 2011;11(5):446–52.CrossRefGoogle Scholar
  17. 17.
    Cycon M, Mrozik A, Piotrowska-Seget Z. Antibiotics in the soil environment-degradation and their impact on microbial activity and diversity. Front Microbiol. 2019;10:338.CrossRefGoogle Scholar
  18. 18.
    World Health Organization. Global action plan on antimicrobial resistance. Geneva, Switzerland: WHO Document Production Services; 2015.Google Scholar
  19. 19.
    van der Weijden GA, Timmerman FA. A systematic review on the clinical efficacy of subgingival debridement in the treatment of chronic periodontitis. J Clin Periodontol. 2002;29(Suppl 3):55–71.CrossRefGoogle Scholar
  20. 20.
    Bragd L, Dahlén G, Wikström M, Slots J. The capability of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius to indicate progressive periodontitis; a retrospective study. J Clin Periodontol. 1987;14(2):95–9.CrossRefGoogle Scholar
  21. 21.
    Grossi SG, Zambon JJ, Ho AW, Koch G, Dunford RG, Machtei EE, et al. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol. 1994;65:260–7.Google Scholar
  22. 22.
    Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal diseases. Periodontol 2000. 1994;5:78–111.CrossRefGoogle Scholar
  23. 23.
    Haffajee AD, Socransky SS, Smith C, Dibart S. Relation of baseline microbial parameters to future periodontal attachment loss. J Clin Periodontol. 1991;18:744–50.CrossRefGoogle Scholar
  24. 24.
    Carlos JP, Wolfe MD, Zambon JJ, Kingman A. Periodontal disease in adolescents: some clinical and microbiologic correlates of attachment loss. J Dent Res. 1988;67:1510–4.CrossRefGoogle Scholar
  25. 25.
    Chaves ES, Jeffcoat MK, Ryerson CC, Snyder B. Persistent bacterial colonization of Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans in periodontitis and its association with alveolar bone loss after 6 months of therapy. J Clin Periodontol. 2000;27(12):897–903.CrossRefGoogle Scholar
  26. 26.
    Rams TE, Listgarten MA, The SJ. Utility of 5 major putative periodontal pathogens and selected clinical parameters to predict periodontal breakdown in adults on maintenance care. J Clin Periodontol. 1996;23:346–54.CrossRefGoogle Scholar
  27. 27.
    Dahlén G, Wikström M, Renvert S. Treatment of periodontal disease based on microbiological diagnosis. A 5-year follow-up on individual patterns. J Periodontol. 1996;67:879–87.CrossRefGoogle Scholar
  28. 28.
    Wennström JL, Dahlén G, Svensson J, Nyman S. Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius: predictors of attachment loss? Oral Microbiol Immunol. 1987;2:158–63.CrossRefGoogle Scholar
  29. 29.
    Mombelli A. Antimicrobial advances in treating periodontal diseases. Front Oral Biol. 2012;15:133–48.CrossRefGoogle Scholar
  30. 30.
    Marsh PD. Plaque as a biofilm: pharmacological principles of drug delivery and action in the sub- and supragingival environment. Oral Dis. 2003;9(Suppl 1):16–22.CrossRefGoogle Scholar
  31. 31.
    Roberts AP, Pratten J, Wilson M, Mullany P. Transfer of a conjugative transposon, Tn5397 in a model oral biofilm. FEMS Microbiol Lett. 1999;177(1):63–6.CrossRefGoogle Scholar
  32. 32.
    Zandbergen D, Slot DE, Cobb CM, Van der Weijden FA. The clinical effect of scaling and root planing and the concomitant administration of systemic amoxicillin and metronidazole: a systematic review. J Periodontol. 2013;84(3):332–51.CrossRefGoogle Scholar
  33. 33.
    Sgolastra F, Gatto R, Petrucci A, Monaco A. 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. 2012;83(10):1257–69.CrossRefGoogle Scholar
  34. 34.
    Sgolastra F, Petrucci A, Gatto R, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis. J Periodontol. 2012;83(6):731–43.CrossRefGoogle Scholar
  35. 35.
    Rooney J, Wade WG, Sprague SV, Newcombe RG, Addy M. Adjunctive effects to non-surgical therapy of systemic metronidazole and amoxycillin alone and combined. A placebo controlled study. J Clin Periodontol. 2002;29:342–50.CrossRefGoogle Scholar
  36. 36.
    Matarazzo F, Figueiredo LC, Cruz SE, Faveri M, Feres M. Clinical and microbiological benefits of systemic metronidazole and amoxicillin in the treatment of smokers with chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol. 2008;35(10):885–96.CrossRefGoogle Scholar
  37. 37.
    Herrera D, Sanz M, Jepsen S, Needleman I, Roldán S. A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol. 2002;29(Suppl.3):136–59.CrossRefGoogle Scholar
  38. 38.
    van Winkelhoff AJ, Winkel EG. Microbiological diagnostics in periodontics. Biological significance and clinical validity. Periodontol 2000. 2005;39:40–52.CrossRefGoogle Scholar
  39. 39.
    Haubek D, Ennibi OK, Poulsen K, Vaeth M, Poulsen S, Kilian M. Risk of aggressive periodontitis in adolescent carriers of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans in Morocco: a prospective longitudinal cohort study. Lancet. 2008;371(9608):237–42.CrossRefGoogle Scholar
  40. 40.
    Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol. 2012;10(10):717–25.CrossRefGoogle Scholar
  41. 41.
    van Winkelhoff AJ, Winkel EG. CommentaryAntibiotics in periodontics: right or wrong? J Periodontol. 2009;80:1555–8.CrossRefGoogle Scholar
  42. 42.
    Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Microbiologic testing and outcomes of full-mouth scaling and root planing with or without amoxicillin/metronidazole in chronic periodontitis. J Periodontol. 2010;81(1):15–23.CrossRefGoogle Scholar
  43. 43.
    Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010;340:c2096.CrossRefGoogle Scholar
  44. 44.
    Cosgarea R, Juncar R, Heumann C, Tristiu R, Lascu L, Arweiler N, et al. 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. 2016;43(9):767–77.Google Scholar
  45. 45.
    Borges I, Faveri M, Figueiredo LC, Duarte PM, Retamal-Valdes B, Montenegro SCL, et al. Different antibiotic protocols in the treatment of severe chronic periodontitis: a 1-year randomized trial. J Clin Periodontol. 2017;44(8):822–32.Google Scholar
  46. 46.
    Cionca N, Giannopoulou C, Ugolotti G, Mombelli A. Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis. J Periodontol. 2009;80:364–71.CrossRefGoogle Scholar
  47. 47.
    Smiley CJ, Tracy SL, Abt E, Michalowicz BS, John MT, Gunsolley J, et al. 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. 2015;146(7):508–24 e5.Google Scholar
  48. 48.
    Heasman PA, Vernazza CR, Gaunt FL, Pennington MA. Cost-effectiveness of adjunctive antimicrobials in the treatment of periodontitis. Periodontol. 2011;55:217–30.CrossRefGoogle Scholar
  49. 49.
    Mombelli A. Maintenance therapy for teeth and implants. Periodontol 2000. 2019;79:190–9.CrossRefGoogle Scholar
  50. 50.
    Metronidazole. https://www.drugs.com/pro/metronidazole. Date accessed: July 8, 2019.
  51. 51.
    Amoxicillin. https://www.drugs.com/pro/amoxicillin. Date accessed: July 8, 2019.
  52. 52.
    Bendesky A, Menendez D, Ostrosky-Wegman P. Is metronidazole carcinogenic? Mutat Res. 2002;511(2):133–44.CrossRefGoogle Scholar
  53. 53.
    Cunha-Cruz J, Hujoel PP, Maupome G, Saver B. Systemic antibiotics and tooth loss in periodontal disease. J Dent Res. 2008;87(9):871–6.CrossRefGoogle Scholar
  54. 54.
    Packer S, Woodley N, Wilson M, Mullany P. Prevalence and persistence of amoxycillin-resistant bacteria in the dental plaques of adults. Microbios. 1999;100(397):135–44.Google Scholar
  55. 55.
    van Winkelhoff AJ, Herrera Gonzales D, Winkel EG, Dellemijn-Kippuw N, Vandenbroucke-Grauls CM, Sanz M. Antimicrobial resistance in the subgingival microflora in patients with adult periodontitis A comparison between The Netherlands and Spain. J Clin Periodontol. 2000;27(2):79–86.CrossRefGoogle Scholar
  56. 56.
    Feres M, Haffajee AD, Allard K, Som S, Goodson JM, Socransky SS. Antibiotic resistance of subgingival species during and after antibiotic therapy. J Clin Periodontol. 2002;29(8):724–35.CrossRefGoogle Scholar
  57. 57.
    Feres M, Haffajee AD, Goncalves C, Allard KA, Som S, Smith C, et al. Systemic doxycycline administration in the treatment of periodontal infections (II). Effect on antibiotic resistance of subgingival species. J Clin Periodontol. 1999;26(12):784–92.Google Scholar
  58. 58.
    Mombelli A, Almaghlouth A, Cionca N, Cancela J, Courvoisier DS, Giannopoulou C. Microbiologic response to periodontal therapy and multivariable prediction of clinical outcome. J Periodontol. 2017;88(12):1253–62.CrossRefGoogle Scholar
  59. 59.
    Mombelli A, Cionca N, Almaghlouth A, Cherkaoui A, Schrenzel J, Giannopoulou C. Effect of periodontal therapy with amoxicillin-metronidazole on pharyngeal carriage of penicillin- and erythromycin-resistant Viridans streptococci. J Periodontol. 2016;87(5):539–47.CrossRefGoogle Scholar
  60. 60.
    Samore MH, Tonnerre C, Hannah EL, Stoddard GJ, Borotkanics RJ, Haddadin B, et al. Impact of outpatient antibiotic use on carriage of ampicillin-resistant Escherichia coli. Antimicrob Agents Chemother. 2011;55(3):1135–41.Google Scholar
  61. 61.
    Smiley CJ, Tracy SL, Abt E, Michalowicz BS, John MT, Gunsolley J, et al. Evidence-based clinical practice guideline on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. J Am Dent Assoc. 2015;146(7):525–35.Google Scholar
  62. 62.
    •• Zandbergen D, Slot DE, Niederman R, Van der Weijden FA. The concomitant administration of systemic amoxicillin and metronidazole compared to scaling and root planing alone in treating periodontitis: a systematic review. BMC Oral Health. 2016;16:27.  https://doi.org/10.1186/s12903-015-0123-6. focused systematic review analyzing differential benefits and risks of adjunctive amoxicillin and metronidazole in various situations.CrossRefGoogle Scholar
  63. 63.
    Esposito M, Grusovin MG, Coulthard P, Worthington HV. Enamel matrix derivative (Emdogain) for periodontal tissue regeneration in intrabony defects. Cochrane Database Syst Rev 2010;(1):CD003875.Google Scholar
  64. 64.
    Needleman IG, Worthington HV, Giedrys-Leeper E, Tucker RJ. Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev 2006(2):CD001724.Google Scholar
  65. 65.
    Mombelli A, Zappa U, Brägger U, Lang NP. Systemic antimicrobial treatment and guided tissue regeneration. Clinical and microbiological effects in furcation defects. J Clin Periodontol. 1996;23:386–96.Google Scholar
  66. 66.
    Mombelli A, Cionca N, Almaghlouth A, Décaillet F, Courvoisier DS, Giannopoulou C. Are there specific benefits of amoxicillin plus metronidazole in Aggregatibacter actinomycetemcomitans-associated periodontitis? Double-masked, randomized clinical trial of efficacy and safety. J Periodontol. 2013;84(6):715–24.CrossRefGoogle Scholar
  67. 67.
    Matuliene G, Pjetursson BE, Salvi GE, Schmidlin K, Brägger U, Zwahlen M, et al. Influence of residual pockets on progression of periodontitis and tooth loss: results after 11 years of maintenance. J Clin Periodontol. 2008;35(8):685–95.Google Scholar
  68. 68.
    Graetz C, Plaumann A, Schlattmann P, Kahl M, Springer C, Salzer S, et al. Long-term tooth retention in chronic periodontitis - results after 18 years of a conservative periodontal treatment regimen in a university setting. J Clin Periodontol. 2017;44(2):169–77.CrossRefGoogle Scholar
  69. 69.
    Graetz C, Salzer S, Plaumann A, Schlattmann P, Kahl M, Springer C, et al. Tooth loss in generalized aggressive periodontitis: prognostic factors after 17 years of supportive periodontal treatment. J Clin Periodontol. 2017;44(6):612–9.CrossRefGoogle Scholar
  70. 70.
    Martinez-Canut P. Predictors of tooth loss due to periodontal disease in patients following long-term periodontal maintenance. J Clin Periodontol. 2015;42(12):1115–25.CrossRefGoogle Scholar
  71. 71.
    Winning L, Linden GJ. Periodontitis and systemic disease: association or causality? Curr Oral Health Rep. 2017;4(1):1–7.CrossRefGoogle Scholar
  72. 72.
    Linden GJ, Lyons A, Scannapieco FA. Periodontal systemic associations: review of the evidence. J Periodontol. 2013;84(4 Suppl):S8–S19.Google Scholar
  73. 73.
    Harding A, Gonder U, Robinson SJ, Crean S, Singhrao SK. Exploring the association between Alzheimer's disease, oral health, microbial endocrinology and nutrition. Front Aging Neurosci. 2017;9:398.CrossRefGoogle Scholar
  74. 74.
    Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, et al. Porphyromonas gingivalis in Alzheimer's disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333.Google Scholar
  75. 75.
    Potempa J, Mydel P, Koziel J. The case for periodontitis in the pathogenesis of rheumatoid arthritis. Nat Rev Rheumatol. 2017;13(10):606–20.CrossRefGoogle Scholar
  76. 76.
    Choi IA, Kim JH, Kim YM, Lee JY, Kim KH, Lee EY, et al. Periodontitis is associated with rheumatoid arthritis: a study with longstanding rheumatoid arthritis patients in Korea. Korean J Intern Med. 2016;31(5):977–86.Google Scholar
  77. 77.
    Bender P, Burgin WB, Sculean A, Eick S. Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis - a systematic review and meta-analysis. Clin Oral Investig. 2017;21(1):33–42.CrossRefGoogle Scholar
  78. 78.
    Lysek RP, Szafraniec K, Polak M, Jankowski P, Micek A, Wolfshaut-Wolak R, et al. Relationship between past myocardial infarction, periodontal disease and Porphyromonas gingivalis serum antibodies: a case-control study. Cardiol J. 2018;25(3):386–92.CrossRefGoogle Scholar
  79. 79.
    • Giannopoulou C, Cionca N, Almaghlouth A, Cancela J, Courvoisier DS, Mombelli A. Systemic biomarkers in 2-phase antibiotic periodontal treatment: a randomized clinical trial. J Dent Res. 2016;95(3):349–55 RCT analyzing systemic effects of adjunctive amoxicillin and metronidazole adjunct to SRP or surgical therapy.CrossRefGoogle Scholar
  80. 80.
    Zekeridou A, Giannopoulou C, Cancela J, Courvoisier D, Mombelli A. Effect of initial periodontal therapy on gingival crevicular fluid cytokine profile in subjects with chronic periodontitis. Clin Exp Dent Res. 2017;3(2):62–8.CrossRefGoogle Scholar
  81. 81.
    Topoll HH, Lange DE, Müller RF. Multiple periodontal abscesses after systemic antibiotic therapy. J Clin Periodontol. 1990;17:268–72.CrossRefGoogle Scholar
  82. 82.
    Herrera D, Retamal-Valdes B, Alonso B, Feres M. Acute periodontal lesions (periodontal abscesses and necrotizing periodontal diseases) and endo-periodontal lesions. J Periodontol. 2018;89(Suppl 1):S85–S102.CrossRefGoogle Scholar
  83. 83.
    Eickholz P, Krigar DM, Pretzl B, Steinbrenner H, Dorfer C, Kim TS. Guided tissue regeneration with bioabsorbable barriers. II. Long-term results in infrabony defects. J Periodontol. 2004;75(7):957–65.CrossRefGoogle Scholar
  84. 84.
    Cortellini P, Tonetti MS. Long-term tooth survival following regenerative treatment of intrabony defects. J Periodontol. 2004;75(5):672–8.CrossRefGoogle Scholar
  85. 85.
    Axelsson P, Nystrom B, Lindhe J. The long-term effect of a plaque control program on tooth mortality, caries and periodontal disease in adults. Results after 30 years of maintenance. J Clin Periodontol. 2004;31(9):749–57.CrossRefGoogle Scholar
  86. 86.
    Axelsson P, Lindhe J. The significance of maintenance care in the treatment of periodontal disease. J Clin Periodontol. 1981;8(4):281–94.CrossRefGoogle Scholar
  87. 87.
    Lindhe J, Westfelt E, Nyman S, Socransky SS, Haffajee AD. Long-term effect of surgical/non-surgical treatment of periodontal disease. J Clin Periodontol. 1984;11:448–58.CrossRefGoogle Scholar
  88. 88.
    World Health Organization. Global action plan on antimicrobial resistance. 2015. https://apps.who.int/iris/handle/10665/193736. Date accessed: July 8, 2019.
  89. 89.
    • Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, et al. Classifying antibiotics in the WHO essential medicines list for optimal use-be AWaRe. Lancet Infect Dis. 2018;18(1):18–20 Classification of antibiotics usable for the empirical treatment of common or severe clinical syndromes.Google Scholar
  90. 90.
    Müller N, Moëne R, Cancela J, Mombelli A. Subgingival air-polishing with erythritol during periodontal maintenance. Randomized clinical trial of twelve months. J Clin Periodontol. 2014;41(9):883–9.CrossRefGoogle Scholar
  91. 91.
    Arweiler NB, Pietruska M, Pietruski J, Skurska A, Dolinska E, Heumann C, et al. Six-month results following treatment of aggressive periodontitis with antimicrobial photodynamic therapy or amoxicillin and metronidazole. Clin Oral Investig. 2014;18(9):2129–35.CrossRefGoogle Scholar
  92. 92.
    Azaripour A, Dittrich S, Van Noorden CJF, Willershausen B. Efficacy of photodynamic therapy as adjunct treatment of chronic periodontitis: a systematic review and meta-analysis. Lasers Med Sci. 2018;33(2):407–23.CrossRefGoogle Scholar
  93. 93.
    Bomfim RA, Frias AC, Pannuti CM, Zilbovicius C, Pereira AC. Socio-economic factors associated with periodontal conditions among Brazilian elderly people - multilevel analysis of the SBSP-15 study. PLoS One. 2018;13(11):e0206730.CrossRefGoogle Scholar
  94. 94.
    Enwonwu CO, Edozien JC. Epidemiology of periodontal disease in Western Nigerians in relation to socio-economic status. Arch Oral Biol. 1970;15(12):1231–44.CrossRefGoogle Scholar
  95. 95.
    Ferrazzano GF, Scaravilli MS, Ingenito A. Dental and periodontal health status in Campanian children and relation between caries experience and socio-economic behavioural factors. Eur J Paediatr Dent. 2006;7(4):174–8.Google Scholar
  96. 96.
    Franklin ER. Periodontal diseases, a grave socio-economic problem in black Africa. Odontostomatol Trop. 1978;1(1):16–28.Google Scholar
  97. 97.
    Gugushe TS. The influence of socio-economic variables on the prevalence of periodontal disease in South Africa. SADJ. 1998;53(2):41–6.Google Scholar
  98. 98.
    Kadtane SS, Bhaskar DJ, Agali C, Punia H, Gupta V, Batra M, et al. Periodontal health status of different socio-economic groups in out-patient department of TMDC & RC, Moradabad, India. J Clin Diagn Res. 2014;8(7):ZC61–4.Google Scholar
  99. 99.
    Klinge B, Norlund A. A socio-economic perspective on periodontal diseases: a systematic review. J Clin Periodontol. 2005;32(Suppl 6):314–25.CrossRefGoogle Scholar
  100. 100.
    Herrera D, Alonso B, Leon R, Roldan S, Sanz M. Antimicrobial therapy in periodontitis: the use of systemic antimicrobials against the subgingival biofilm. J Clin Periodontol. 2008;35(8 Suppl):45–66.CrossRefGoogle Scholar
  101. 101.
    Kaner D, Christan C, Dietrich T, Bernimoulin JP, Kleber BM, Friedmann A. Timing affects the clinical outcome of adjunctive systemic antibiotic therapy for generalized aggressive periodontitis. J Periodontol. 2007;78(7):1201–8.CrossRefGoogle Scholar
  102. 102.
    Griffiths GS, Ayob R, Guerrero A, Nibali L, Suvan J, Moles DR, et al. Amoxicillin and metronidazole as an adjunctive treatment in generalized aggressive periodontitis at initial therapy or re-treatment: a randomized controlled clinical trial. J Clin Periodontol. 2011;38(1):43–9.Google Scholar
  103. 103.
    Mombelli A, Almaghlouth A, Cionca N, Courvoisier DS, Giannopoulou C. Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial. J Periodontol. 2015;86:367–75.CrossRefGoogle Scholar
  104. 104.
    Mestnik MJ, Feres M, Figueiredo LC, Soares G, Teles RP, Fermiano D, et al. The effects of adjunctive metronidazole plus amoxicillin in the treatment of generalized aggressive periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012;39(10):955–61.Google Scholar
  105. 105.
    Feres M, Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, et al. 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. 2012;39(12):1149–58.CrossRefGoogle Scholar
  106. 106.
    Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, et al. Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol. 2005;32(10):1096–107.Google Scholar
  107. 107.
    Thomas C, Stevenson M, Riley TV. Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review. J Antimicrob Chemother. 2003;51(6):1339–50.CrossRefGoogle Scholar
  108. 108.
    Mombelli A, Cionca N, Almaghlouth A. Does adjunctive antimicrobial therapy reduce the perceived need for periodontal surgery? Periodontol. 2011;55(1):205–16.CrossRefGoogle Scholar
  109. 109.
    Mombelli A, Schmid J, Walther C, Wetzel A. Qualitätsleitlinien Parodontologie. Swiss Dental J. 2014;124(2):261–7.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.University Clinic of Dental Medicine Division of PeriodontologyUniversity of GenevaGeneva 4Switzerland

Personalised recommendations