An estimate of pocket closure and avoided needs of surgery after scaling and root planing with systemic antibiotics: A systematic review

BMC Oral Health

Volumn 14, Issue 1, 2014, Pages

  Kolakovic, Mirela ^a   Held, Ulrike ^b   Schmidlin, Patrick R ^a   Sahrmann, Philipp ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Amoxicillin; Antibiotics; Metronidazole; Non surgical therapy; Periodontitis; Treatment needs

Indexed keywords

AMOXICILLIN; ANTIINFECTIVE AGENT; DRUG COMBINATION; METRONIDAZOLE;

AGGRESSIVE PERIODONTITIS; CHRONIC PERIODONTITIS; DENTAL SCALING; DRUG COMBINATION; HUMAN; MULTIMODALITY CANCER THERAPY; PERIODONTAL POCKET; PROCEDURES; ROOT PLANING;

AGGRESSIVE PERIODONTITIS; AMOXICILLIN; ANTI-BACTERIAL AGENTS; CHRONIC PERIODONTITIS; COMBINED MODALITY THERAPY; DENTAL SCALING; DRUG COMBINATIONS; HUMANS; METRONIDAZOLE; PERIODONTAL POCKET; ROOT PLANING;

EID: 84939568056     PISSN: None     EISSN: 14726831     Source Type: Journal    
DOI: 10.1186/1472-6831-14-159     Document Type: Article

References (100)

1. Loe H: Principles of aetiology and pathogenesis governing the treatment of periodontal disease. Int Dent J 1983, 33: 119-126.
2. Oliver RC, Brown LJ, Loe H: Periodontal diseases in the United States population. J Periodontol 1998, 69: 269-278. 10.1902/jop.1998.69.2.269.
3. Albandar JM, Rams TE: Global epidemiology of periodontal diseases: an overview. Periodontol 2000 2002, 29: 7-10. 10.1034/j.1600-0757.2002.290101.x.
4. Heitz-Mayfield LJ, Lang NP: Comparative biology of chronic and aggressive periodontitis vs. peri-implantitis. Periodontol 2000 2010, 53: 167-181. 10.1111/j.1600-0757.2010.00348.x.
5. Socransky SS: Microbiology of periodontal disease - present status and future considerations. J Periodontol 1977, 48: 497-504. 10.1902/jop.1977.48.9.497.
6. Periodontics AAPWWi: Consensus report. Periodontal diseases: pathogenesis and microbial factors. Ann Periodontol 1996, 1: 926-932.
7. Badersten A, Nilveus R, Egelberg J: Effect of nonsurgical periodontal therapy. I. Moderately advanced periodontitis. J Clin Periodontol 1981, 8: 57-72. 10.1111/j.1600-051X.1981.tb02024.x.
8. Magnusson I, Lindhe J, Yoneyama T, Liljenberg B: Recolonization of a subgingival microbiota following scaling in deep pockets. J Clin Periodontol 1984, 11: 193-207. 10.1111/j.1600-051X.1984.tb01323.x.
9. Westfelt E, Rylander H, Dahlen G, Lindhe J: The effect of supragingival plaque control on the progression of advanced periodontal disease. J Clin Periodontol 1998, 25: 536-541. 10.1111/j.1600-051X.1998.tb02484.x.
10. Caffesse RG, Sweeney PL, Smith BA: Scaling and root planing with and without periodontal flap surgery. J Clin Periodontol 1986, 13: 205-210. 10.1111/j.1600-051X.1986.tb01461.x.
11. Brayer WK, Mellonig JT, Dunlap RM, Marinak KW, Carson RE: Scaling and root planing effectiveness: the effect of root surface access and operator experience. J Periodontol 1989, 60: 67-72. 10.1902/jop.1989.60.1.67.
12. Hirschfeld L, Wasserman B: A long-term survey of tooth loss in 600 treated periodontal patients. J Periodontol 1978, 49: 225-237. 10.1902/jop.1978.49.5.225.
13. Adriaens PA, Adriaens LM: Effects of nonsurgical periodontal therapy on hard and soft tissues. Periodontol 2000 2004, 36: 121-145. 10.1111/j.1600-0757.2004.03676.x.
14. Morrison EC, Ramfjord SP, Hill RW: Short-term effects of initial, nonsurgical periodontal treatment (hygienic phase). J Clin Periodontol 1980, 7: 199-211. 10.1111/j.1600-051X.1980.tb01963.x.
15. Fleischer HC, Mellonig JT, Brayer WK, Gray JL, Barnett JD: Scaling and root planing efficacy in multirooted teeth. J Periodontol 1989, 60: 402-409. 10.1902/jop.1989.60.7.402.
16. Mombelli A, Samaranayake LP: Topical and systemic antibiotics in the management of periodontal diseases. Int Dent J 2004, 54: 3-14. 10.1111/j.1875-595X.2004.tb00246.x.
17. Quirynen M, De Soete M, Dierickx K, van Steenberghe D: The intra-oral translocation of periodontopathogens jeopardises the outcome of periodontal therapy. A review of the literature. J Clin Periodontol 2001, 28: 499-507. 10.1034/j.1600-051x.2001.028006499.x.
18. Muller HP, Heinecke A, Fuhrmann A, Eger T, Zoller L: Intraoral distribution of Actinobacillus actinomycetemcomitans in young adults with minimal periodontal disease. J Periodontal Res 2001, 36: 114-123. 10.1034/j.1600-0765.2001.360208.x.
19. Rudney JD, Chen R, Sedgewick GJ: Intracellular Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in buccal epithelial cells collected from human subjects. Infect Immun 2001, 69: 2700-2707. 10.1128/IAI.69.4.2700-2707.2001.
20. Blix IJ, Hars R, Preus HR, Helgeland K: Entrance of Actinobacillus actinomycetemcomitans into HEp-2 cells in vitro. J Periodontol 1992, 63: 723-728. 10.1902/jop.1992.63.9.723.
21. Sreenivasan PK, Meyer DH, Fives-Taylor PM: Requirements for invasion of epithelial cells by Actinobacillus actinomycetemcomitans. Infect Immun 1993, 61: 1239-1245.
22. OSTRANDER FD: Vitamins, sulfonamides and antibiotics in periodontal therapy. J Am Dent Assoc 1948, 37: 279-288. 10.14219/jada.archive.1948.0193.
23. Slots J, Ting M: Systemic antibiotics in the treatment of periodontal disease. Periodontol 2000 2002, 28: 106-176. 10.1034/j.1600-0757.2002.280106.x.
24. Mombelli A, Cionca N, Almaghlouth A, Decaillet 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: 715-724. 10.1902/jop.2012.120281.
25. Veloo AC, Seme K, Raangs E, Rurenga P, Singadji Z, Wekema-Mulder G, van Winkelhoff AJ: Antibiotic susceptibility profiles of oral pathogens. Int J Antimicrob Agents 2012, 40: 450-454. 10.1016/j.ijantimicag.2012.07.004.
26. Matuliene G, Studer R, Lang NP, Schmidlin K, Pjetursson BE, Salvi GE, Bragger U, Zwahlen M: Significance of Periodontal Risk Assessment in the recurrence of periodontitis and tooth loss. J Clin Periodontol 2010, 37: 191-199. 10.1111/j.1600-051X.2009.01508.x.
27. Ainamo J, Barmes D, Beagrie G, Cutress T, Martin J, Sardo-Infirri J: Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). Int Dent J 1982, 32: 281-291.
28. Nasi JH: Background to, and implementation of, the Periodontal Screening and Recording (PSR) procedure in the USA. Int Dent J 1994, 44: 585-588.
29. Moher D, Liberati A, Tetzlaff J, Altman DG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009, 339: b2535. 10.1136/bmj.b2535.
30. 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: 332-351. 10.1902/jop.2012.120040.
31. 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: 1257-1269. 10.1902/jop.2012.110625.
32. Hauri D, Schmidlin PR, Puhan MA: Development of an easily interpretable presentation format for meta-analyses in periodontal surgery. Evid Based Dent 2008, 9: 89-90. 10.1038/sj.ebd.6400604.
33. RCT: R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2013. URL. http://wwwR-project.org URL.
34. Akincibay H, Orsal SO, Sengun D, Tozum TF: Systemic administration of doxycycline versus metronidazole plus amoxicillin in the treatment of localized aggressive periodontitis: a clinical and microbiologic study. Quintessence Int 2008, 39: e33-9.
35. Carvalho LH, D'Avila GB, Leao A, Goncalves C, Haffajee AD, Socransky SS, Feres M: Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population II-microbiological results. J Clin Periodontol 2005, 32: 406-411. 10.1111/j.1600-051X.2005.00720.x.
36. 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: 15-23. 10.1902/jop.2009.090390.
37. Ehmke B, Beikler T, Haubitz I, Karch H, Flemmig TF: Multifactorial assessment of predictors for prevention of periodontal disease progression. Clin Oral Investig 2003, 7: 217-221. 10.1007/s00784-003-0227-2.
38. Ehmke B, Moter A, Beikler T, Milian E, Flemmig TF: Adjunctive antimicrobial therapy of periodontitis: long-term effects on disease progression and oral colonization. J Periodontol 2005, 76: 749-759. 10.1902/jop.2005.76.5.749.
39. Eickholz P, Siegelin Y, Scharf S, Schacher B, Oremek GM, Sauer-Eppel H, Schubert R, Wohlfeil M: Non-surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis. J Clin Periodontol 2013, 40: 327-333. 10.1111/jcpe.12076.
40. Eisenberg L, Suchow R, Coles RS, Deasy MJ: The effects of metronidazole administration on clinical and microbiologic parameters of periodontal disease. Clin Prev Dent 1991, 13: 28-34.
41. Feres M, Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS, Figueiredo LC: 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: 1149-1158. 10.1111/jcpe.12004.
42. Flemmig TF, Milian E, Karch H, Klaiber B: Differential clinical treatment outcome after systemic metronidazole and amoxicillin in patients harboring Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis. J Clin Periodontol 1998, 25: 380-387. 10.1111/j.1600-051X.1998.tb02459.x.
43. Haffajee AD, Patel M, Socransky SS: Microbiological changes associated with four different periodontal therapies for the treatment of chronic periodontitis. Oral Microbiol Immunol 2008, 23: 148-157. 10.1111/j.1399-302X.2007.00403.x.
44. Hartmann J, Muller HP, Flores-de-Jacoby L: Systemic metronidazole therapy and/or subgingival scaling and root planing. II. Development of clinical parameters in relation to the changes in the composition of the associated subgingival microflora. Dtsch Zahnarztl Z 1986, 41: 579-584.
45. Hernandez E, Castella R: Metronidazol en el tratamiento de la enfermedad periodontal. Practica Odontologica 1987, 8: 34-38.
46. Jenkins WM, MacFarlane TW, Gilmour WH, Ramsay I, MacKenzie D: Systemic metronidazole in the treatment of periodontitis. J Clin Periodontol 1989, 16: 443-450. 10.1111/j.1600-051X.1989.tb01673.x.
47. Joyston-Bechal S, Smales FC, Duckworth R: Effect of metronidazole on chronic periodontal disease in subjects using a topically applied chlorhexidine gel. J Clin Periodontol 1984, 11: 53-62. 10.1111/j.1600-051X.1984.tb01308.x.
48. Joyston-Bechal S, Smales FC, Duckworth R: A follow-up study 3 years after metronidazole therapy for chronic periodontal disease. J Clin Periodontol 1986, 13: 944-949. 10.1111/j.1600-051X.1986.tb01432.x.
49. Lindhe J, Westfelt E, Nyman S, Socransky SS, Heijl L, Bratthall G: Healing following surgical/non-surgical treatment of periodontal disease. A clinical study. J Clin Periodontol 1982, 9: 115-128. 10.1111/j.1600-051X.1982.tb01227.x.
50. Loesche WJ, Schmidt E, Smith BA, Caffessee R, Stoll J: Metronidazole therapy for periodontitis. J Periodontal Res 1987, 22: 224-226. 10.1111/j.1600-0765.1987.tb01574.x.
51. Loesche WJ, Giordano JR, Hujoel P, Schwarcz J, Smith BA: Metronidazole in periodontitis: reduced need for surgery. J Clin Periodontol 1992, 19: 103-112. 10.1111/j.1600-051X.1992.tb00448.x.
52. Loesche WJ, Grossman N, Giordano J: Metronidazole in periodontitis (IV). The effect of patient compliance on treatment parameters. J Clin Periodontol 1993, 20: 96-104. 10.1111/j.1600-051X.1993.tb00336.x.
53. Lu RF, Xu L, Feng XH, Meng HX: [Short term effect of combined use of amoxicillin and metronidazole at different time of non-surgical periodontal treatment for aggressive periodontitis]. Zhonghua Kou Qiang Yi Xue Za Zhi 2012, 47: 666-670.
54. Lundstrom A, Johansson LA, Hamp SE: Effect of combined systemic antimicrobial therapy and mechanical plaque control in patients with recurrent periodontal disease. J Clin Periodontol 1984, 11: 321-330. 10.1111/j.1600-051X.1984.tb01328.x.
55. Mombelli A, Brochut P, Plagnat D, Casagni F, Giannopoulou C: Enamel matrix proteins and systemic antibiotics as adjuncts to non-surgical periodontal treatment: clinical effects. J Clin Periodontol 2005, 32: 225-230. 10.1111/j.1600-051X.2005.00664.x.
56. Sigusch B, Pfister W, Klinger G, Glockmann E: [Adjuvant antibiotic therapy as a 2-step treatment concept in early-onset periodontitis: a strategy for eradication of bacteria that cause periodontitis]. Dtsch Med Wochenschr 2000, 125: 1186-1191. 10.1055/s-2000-7699.
57. Sigusch B, Beier M, Klinger G, Pfister W, Glockmann E: A 2-step non-surgical procedure and systemic antibiotics in the treatment of rapidly progressive periodontitis. J Periodontol 2001, 72: 275-283. 10.1902/jop.2001.72.3.275.
58. Stahel WA: Statistische Datenanalyse. Eine Einführung für Naturwissenschaftler. Vieweg, Braunschweig: 2002. 4th edition: ch 4.9
59. Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, Tonetti MS: 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: 1096-1107. 10.1111/j.1600-051X.2005.00814.x.
60. Loesche WJ, Schmidt E, Smith BA, Morrison EC, Caffesse R, Hujoel PP: Effects of metronidazole on periodontal treatment needs. J Periodontol 1991, 62: 247-257. 10.1902/jop.1991.62.4.247.
61. Aimetti M, Romano F, Guzzi N, Carnevale G: Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial. J Clin Periodontol 2012, 39: 284-294. 10.1111/j.1600-051X.2011.01795.x.
62. Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA, Faveri M: Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol 2010, 37: 353-365. 10.1111/j.1600-051X.2010.01538.x.
63. Moeintaghavi A, Talebi-ardakani MR, Haerian-ardakani A, Zandi H, Taghipour S, Fallahzadeh H, Pakzad A, Fahami N: Adjunctive effects of systemic amoxicillin and metronidazole with scaling and root planing: a randomized, placebo controlled clinical trial. J Contemp Dent Pract 2007, 8: 51-59.
64. Ribeiro Edel P, Bittencourt S, Zanin IC, Bovi Ambrosano GM, Sallum EA, Nociti FH, Goncalves RB, Casati MZ: Full-mouth ultrasonic debridement associated with amoxicillin and metronidazole in the treatment of severe chronic periodontitis. J Periodontol 2009, 80: 1254-1264. 10.1902/jop.2009.080403.
65. 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: 885-896. 10.1111/j.1600-051X.2008.01304.x.
66. Berglundh T, Krok L, Liljenberg B, Westfelt E, Serino G, Lindhe J: The use of metronidazole and amoxicillin in the treatment of advanced periodontal disease. A prospective, controlled clinical trial. J Clin Periodontol 1998, 25: 354-362. 10.1111/j.1600-051X.1998.tb02455.x.
67. Carvalho LH, D'Avila GB, Leao A, Haffajee AD, Socransky SS, Feres M: Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population. I. clinical results. J Clin Periodontol 2004, 31: 1070-1076. 10.1111/j.1600-051X.2004.00605.x.
68. 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: 364-371. 10.1902/jop.2009.080540.
69. Haffajee AD, Torresyap G, Socransky SS: Clinical changes following four different periodontal therapies for the treatment of chronic periodontitis: 1-year results. J Clin Periodontol 2007, 34: 243-253. 10.1111/j.1600-051X.2006.01040.x.
70. Heller D, Varela VM, Silva-Senem MX, Torres MC, Feres-Filho EJ, Colombo AP: Impact of systemic antimicrobials combined with anti-infective mechanical debridement on the microbiota of generalized aggressive periodontitis: a 6-month RCT. J Clin Periodontol 2011, 38: 355-364. 10.1111/j.1600-051X.2011.01707.x.
71. Rooney J, Wade WG, Sprague SV, Newcombe RG, Addy M: Adjunctive effects to non-surgical periodontal therapy of systemic metronidazole and amoxycillin alone and combined. A placebo controlled study. J Clin Periodontol 2002, 29: 342-350. 10.1034/j.1600-051X.2002.290410.x.
72. Soder B, Nedlich U, Jin LJ: Longitudinal effect of non-surgical treatment and systemic metronidazole for 1 week in smokers and non-smokers with refractory periodontitis: a 5-year study. J Periodontol 1999, 70: 761-771. 10.1902/jop.1999.70.7.761.
73. Winkel EG, van Winkelhoff AJ, Barendregt DS, van der Weijden GA, Timmerman MF, van der Velden U: Clinical and microbiological effects of initial periodontal therapy in conjunction with amoxicillin and clavulanic acid in patients with adult periodontitis. A randomised double-blind, placebo-controlled study. J Clin Periodontol 1999, 26: 461-468. 10.1034/j.1600-051X.1999.260708.x.
74. Winkel EG, Van Winkelhoff AJ, Timmerman MF, Van der Velden U, Van der Weijden GA: Amoxicillin plus metronidazole in the treatment of adult periodontitis patients. A double-blind placebo-controlled study. J Clin Periodontol 2001, 28: 296-305. 10.1034/j.1600-051x.2001.028004296.x.
75. Xajigeorgiou C, Sakellari D, Slini T, Baka A, Konstantinidis A: Clinical and microbiological effects of different antimicrobials on generalized aggressive periodontitis. J Clin Periodontol 2006, 33: 254-264. 10.1111/j.1600-051X.2006.00905.x.
76. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF: Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses. Lancet 1999, 354: 1896-1900. 10.1016/S0140-6736(99)04149-5.
77. Schmidlin PR, Hauri D, Krahenmann MA, Puhan MA, Attin T: Residual pocket depth after periodontal regenerative procedures. Clinical relevance and interpretation of meta-analyses data. Schweiz Monatsschr Zahnmed 2009, 119: 224-231.
78. Mestnik MJ, Feres M, Figueiredo LC, Soares G, Teles RP, Fermiano D, Duarte PM, Faveri M: 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: 955-961. 10.1111/j.1600-051X.2012.01932.x.
79. 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: 1201-1208. 10.1902/jop.2007.060437.
80. Griffiths GS, Ayob R, Guerrero A, Nibali L, Suvan J, Moles DR, Tonetti MS: 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: 43-49. 10.1111/j.1600-051X.2010.01632.x.
81. Anon: rescribing information. Amoxicillin Sandoz (amoxicillin). (accessed March 2014) http://compendium.ch/mpro/mnr/15125/html/de
82. Mombelli A, Cionca N, Almaghlouth A: Does adjunctive antimicrobial therapy reduce the perceived need for periodontal surgery? Periodontol 2000 2011, 55: 205-216. 10.1111/j.1600-0757.2010.00356.x.
83. Ardila CM, Granada MI, Guzman IC: Antibiotic resistance of subgingival species in chronic periodontitis patients. J Periodontal Res 2010, 45: 557-563.
84. Giannopoulou C, Andersen E, Brochut P, Plagnat D, Mombelli A: Enamel matrix derivative and systemic antibiotics as adjuncts to non-surgical periodontal treatment: biologic response. J Periodontol 2006, 77: 707-713. 10.1902/jop.2006.050166.
85. Moreira RM, Feres-Filho EJ: Comparison between full-mouth scaling and root planing and quadrant-wise basic therapy of aggressive periodontitis: 6-month clinical results. J Periodontol 2007, 78: 1683-1688. 10.1902/jop.2007.060354.
86. Muller HP, Hartmann J, Flores-de-Jacoby L: Systemic metronidazole therapy and/or subgingival scaling with root planing. I. Clinical results. Dtsch Zahnarztl Z 1986, 41: 573-578.
87. Noyan U, Yilmaz S, Kuru B, Kadir T, Acar O, Buget E: A clinical and microbiological evaluation of systemic and local metronidazole delivery in adult periodontitis patients. J Clin Periodontol 1997, 24: 158-165. 10.1111/j.1600-051X.1997.tb00485.x.
88. Palmer RM, Matthews JP, Wilson RF: Adjunctive systemic and locally delivered metronidazole in the treatment of periodontitis: a controlled clinical study. Br Dent J 1998, 184: 548-552. 10.1038/sj.bdj.4809695.
89. Palmer RM, Scott DA, Meekin TN, Poston RN, Odell EW, Wilson RF: Potential mechanisms of susceptibility to periodontitis in tobacco smokers. J Periodontal Res 1999, 34: 363-369. 10.1111/j.1600-0765.1999.tb02267.x.
90. Re G, Barbero P, Briccarello MP, Manzon W, Zoccola GC: Oral amoxicillin 1g b.i.d vs 1g t.i.d. in the treatment of oral periodontitis. Randomized and double-blind pilot trial. Minerva Stomatol 1988, 37: 507-509.
91. Soder PO, Frithiof L, Wikner S, Wouters F, Engstrom PE, Rubin B, Nedlich U, Soder B: The effect of systemic metronidazole after non-surgical treatment in moderate and advanced periodontitis in young adults. J Periodontol 1990, 61: 281-288. 10.1902/jop.1990.61.5.281.
92. Sterry KA, Langeroudi M, Dolby AE: Metronidazole as an adjunct to periodontal therapy with sub-gingival curettage. Br Dent J 1985, 158: 176-178. 10.1038/sj.bdj.4805568.
93. Tinoco EM, Beldi MI, Campedelli F, Lana M, Loureiro CA, Bellini HT, Rams TE, Tinoco NM, Gjermo P, Preus HR: Clinical and microbiological effects of adjunctive antibiotics in treatment of localized juvenile periodontitis. A controlled clinical trial. J Periodontol 1998, 69: 1355-1363. 10.1902/jop.1998.69.12.1355.
94. Varela VM, Heller D, Silva-Senem MX, Torres MC, Colombo AP, Feres-Filho EJ: Systemic antimicrobials adjunctive to a repeated mechanical and antiseptic therapy for aggressive periodontitis: a 6-month randomized controlled trial. J Periodontol 2011, 82: 1121-1130. 10.1902/jop.2011.100656.
95. Vergani SA, Silva EB, Vinholis AH, Marcantonio RA: Systemic use of metronidazole in the treatment of chronic periodontitis: a pilot study using clinical, microbiological, and enzymatic evaluation. Braz Oral Res 2004, 18: 121-127.
96. Casarin RC, Peloso Ribeiro ED, Sallum EA, Nociti FHJ, Goncalves RB, Casati MZ: The combination of amoxicillin and metronidazole improves clinical and microbiologic results of one-stage, full-mouth, ultrasonic debridement in aggressive periodontitis treatment. J Periodontol 2012, 83: 988-998. 10.1902/jop.2012.110513.
97. Goodson JM, Haffajee AD, Socransky SS, Kent R, Teles R, Hasturk H, Bogren A, Van Dyke T, Wennstrom J, Lindhe J: Control of periodontal infections: a randomized controlled trial I. The primary outcome attachment gain and pocket depth reduction at treated sites. J Clin Periodontol 2012, 39: 526-536. 10.1111/j.1600-051X.2012.01870.x.
98. Mdala I, Haffajee AD, Socransky SS, de Blasio BF, Thoresen M, Olsen I, Goodson JM: Multilevel analysis of clinical parameters in chronic periodontitis after root planing/scaling, surgery, and systemic and local antibiotics: 2-year results. J Oral Microbiol 2012, 4:. doi:10.3402 doi:10.3402
99. Preus HR, Gunleiksrud TM, Sandvik L, Gjermo P, Baelum V: A randomized, double-masked clinical trial comparing four periodontitis treatment strategies: 1-year clinical results. J Periodontol 2013, 84: 1075-1086. 10.1902/jop.2012.120400.
100. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1472-6831/14/159/prepub