65. Etiology - Local Plaque Control- C   chemical agents                                  

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  1. Evidence Based Review
  2. Chlorhexidine
  3. Listerine
  4. Triclosan
  5. Medicaments - Fluorides
  6. Miscellaneous Compounds
  7. Comparative chemical agent studies
  8. Antibiotics
    1. Review of Concept
    2. Rationale for use
    3. Resistance
    4. Combination therapy
    5. Tetracyclines
    6. Macrolides
    7. Fluoroquinolones
    8. Augmentin

Evidence Based Review

  1. Gunsolley, J. A meta analysis of six-month studies of antiplaque and antigingivitis agents. J Am Dent Assoc. 2006 Dec; 137 (12):1649-57

Chlorhexidine

  1. Greenstein G, et al: Chlorhexidine: An adjunct to periodontal therapy. J Periodontol 57:370, 1986. (Review)

  2. Newman, M., et al: Effect of 0.12% chlorhexidine on bacterial recolonization following periodontal surgery. J. Periodontol 60: 577 – 581, 1989

  3. Quirynen M, Mongardini C, De Soete M, Pauwels M, Coucke W, Van Eldere J,Van Steenberghe D. The roˆle of chlorhexidine in the one stage full-mouth disinfection treatment of patients with advanced adult periodontitis. Long-term clinical andmicrobiological observations. J Clin Periodontol 2000; 27: 578–589.

  4. Zanatta F et al: The effect of 0.12% chlorhexidine gluconate rinsing on previously plaque-free and plaque-covered surfaces: a randomized, controlled clinical trial. J Periodontol 2007:78;2127-2134

  5. Faveri M, Gursky LC, Feres M, Shibli JA, Salvador SL, de Figueiredo LC. Scaling and root planing and chlorhexidine mouthrinses in the treatment of chronic periodontitis: a randomized, placebo-controlled clinical trial. J Clin Periodontol 2006; 33: 819–828.

Listerine

  1. Cortelli SC, Cortelli JR, Holzhausen M, Franco GCN, Rebelo RZ, Sonagere AS, Queiroz CS, Costa FO. Essential oils in one stage full-mouth disinfection: doubleblind, randomized clinical trial of long-term clinical, microbial and salivary effects. J Clin Periodontol 2009; 36: 333–342

  2. Bauroth K, Charles CH, et al. The efficacy of an essential oil antiseptic mouthrinse vs. dental floss in controlling interproximal gingivitis. A comparative study. JADA 134:359-65, 2003.

  3. Sharma N, Charles CH, Lynch MC, Qaqish J, McGuire JA, Galustians JG, Kumar LD. Adjunctive benefit of an essential oil-containing mouthrinse in reducing plaque and gingivitis in patients who brush and floss regularly: a six-month study. J Am Dent Assoc. 2004 Apr;135(4):496-504.

  4. Stoeken JE, Paraskevas S, van der Weijden GA. The long-term effect of a mouthrinse containing essential oils on dental plaque and gingivitis: a systematic review. J Periodontol. 2007 Jul;78(7):1218-28.

  5. Ioannis Tsourounakis, Angela A. Palaiologou-Gallis, Diana Stoute, Pooja Maney, Thomas E Lallier. Effect of Essential Oil and Chlorhexidine Mouthwashes on Gingival Fibroblast Survival and Migration. Journal of Periodontology August 2013, Vol. 84, No. 8, Pages 1211-1220

Triclosan

  1. Rosling, B et al: The use of triclosancopolymer dentifrice may retard the progression of periodontitis. J Clin Periodontol 24: 873 – 880, 1997

  2. Rosling, B et al: Effect of triclosan on the subgingival microbiota of periodontitis – susceptible subjects. J Clin Periodonto 24:881-887, 1997

Medicaments - Fluorides

  1. Ciancio SG, et al.: Clinical effects of a stannous fluoride mouthrinse on plaque. Clin. Prev. Dent. 14(5):27-30, 1992.

  2. Bacca LA, et al. A comparison of intraoral antimicrobial effects of stabilized stannous fluoride dentifrice, baking soda/peroxide dentifrice, conventional NaF dentifrice and essential oil mouthrinse. J Clin Dent 1997; 8: 54-61

Miscellaneous

  1. Caton, J et al: Comparison between mechanical cleaning and an antimicrobial rinse for the treatment and prevention of interdental gingivitis. J Clin Periodontol 20: 172 – 178, 1993

  2. Van der Weijden GA, Timmer CJ, et al. The effect of herbal extracts in an experimental mouthrinse on established plaque and gingivitis. J Clin Periodontol 25:399-403, 1998.

  3. Greenstein, G: Povidone-iodine’s effects and role in the management of periodontal diseases: A review. J Periodontol 70: 1397-1405, 1999

  4. Arweiler NB, Netuschil L, Reich E. Alcohol-free mouthrinse solutions to reduce supragingival plaque regrowth and vitality. A controlled clinical study. J Clin Periodontol 28:168-74, 2001

  5. Sreenivasa P, Gaffar A. Antiplaque biocides and bacterial resistance: a review. J Clin Periodontol 29:965-974, 2002. (Review)

Comparative studies

  1. Wennstrom J, Lindhe J: The effect of mouthrinses on parameters characterizing human periodontal disease. J. Clin. Periodontol. 13:86-93, 1986.

  2. Axelsson P, Lindhe J: Efficacy of mouthrinses in inhibiting dental plaque and gingivitis in man. J. Clin. Periodontol. 14: 205 -212, 1987

  3. Grossman E, Meckel AH, Isaacs RL, et al.: A clinical comparison of antibacterial mouthrinses: Effect of chlorhexidine, phenolics, and sanguinarine on dental plaque and gingivitis. J. Periodontol.60:435-440, 1989.

  4. Gultz J, Kaim J, DeLeo J, Scherer W. An in vivo comparison of the antimicrobial activities of three mouthrinses. J Clin Dent 9:43-45, 1998.

  5. Pan PH, Finnegan MB, Sturdivant L, Barnett ML. Comparative antimicrobial activity of an essential oil and an amine flouride/stannous fluoride mouthrinse in vitro. J Clin Periodontol 26:474-476, 1999.

Antibiotics Review of Concept

  1. Slots, J et al: Systemic antibiotics in the treatment of periodontal disease. Periodontol 2000; 28: 106 – 176, 2001

  2. Walker, c et al: Rationale for use of antibiotics in Periodontics. J Periodontol; 2002 Oct; 73 (10): 1188

  3. Haffajee AD, Socransky SS, Gunsolley JC. Systemic anti-infective periodontal therapy. A systematic review. Ann Periodontol 2003; 8: 115-181 (Review)

  4. Listgarten M, Loomer, P: Microbial identification in the management of periodontal disease. A systematic 33 review. Ann Periodontol, 2003: Dec; 8 (1): 115 – 81

  5. AAP Position Paper: Systemic antibiotics in Periodontics. J Periodonto 2004; 75: 1553 – 1565

Antibiotics- Rationale

  1. 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 May;76(5):749-59.

  2. Haffajee A et al: Clinical changes following four different periodontal therapies for the treatment of chronic periodontitis: 1 year results. J Clin Periodonto 2007; 34: 243 – 253

Antibiotic-Resistance

  1. Walker, C: The acquisition of antibiotic resistance in the periodontal microflora. Periodontolgy 2000: 10: 79 – 88, 1996

Antibiotics-Combination therapy

  1. Matarazzo F, et al: Clincial and microbiological benefits of systemic metronidazole and amoxicillin in the treatment of smokers with chronic periodontitis; A randomized placebo – controlled study. J Clin Periodonto 2008; 35: 885 – 896

  2. Lopez NJ, Socransky SS, Da Silva I, Japlit MR, Haffajee AD. Effects of metronidazole plus amoxicillin as the only therapy on the microbiological and clinical parameters of untreated chronic periodontitis. J Clin Periodontol 2006; 33: 648–660

 Antibiotics-Tetracycline  

  1. Sakellari D, Goodson JM, Socransky SS, Kolokotronis A, Konstantinidis A: Concentration of 3 tetracyclines in plasma, gingival crevice fluid and saliva. J Clin Periodontol 2000; 27: 53–60.

  2. Rodrigues RMJ, Gonc¸alves C, Souto R, Feres-Filho EJ, Uzeda M, Colombo APV: Antibiotic resistance profile of the subgingival microbiota following systemic or local tetracycline therapy. J Clin Periodontol 2004; 31: 420–427.

  3. Ramberg P, Rosling B, Serino G, Hellstro¨m M-K, Socransky SS, Lindhe J:The long-term effect of systemic tetracycline used as an adjunct to non-surgicaltreatment of advanced periodontitis. J Clin Periodontol 2001; 28: 446–452.

Macrolides

  1. Mascarenhas Paulo , Ricardo Gapski, Khalaf Al-Shammari, Roger Hill, Stephen Soehren, Christopher Fenno, William V. Giannobile, and Hom-Lay Wang . Clinical Response of Azithromycin as an Adjunct to Non-Surgical Periodontal Therapy in Smokers J. Periodontol 2005;76:426-436.

  2. Akihiro Yashima, Kazuhiro Gomi, Nobuko Maeda, and Takashi Arai One-Stage Full-Mouth Versus Partial-Mouth Scaling and Root Planing During the Effective Half-Life of Systemically Administered Azithromycin J Periodontol 2009;80: 1406-1413.

Fluoroquinolones

  1. Conway, T ; Gingival Fluid Ciprofloxacin Levels at Healthy and Inflamed Human Periodontal Sites September 2000, Vol. 71, No. 9, Pages 1448-1452

Antibiotics – Augmentin

  1. Winkel, E., Van Winklehoff, et al: Clinical and microbiological effects of initial periodontal therapy in conjunction with amoxicillin and clavulanic acid in patients with adult periodontitis. A randomized double-blind placebo controlled study. J Clin Periodonto 26: 461 – 468, 1999

Evidence Based Review

 

Gunsolley, 2006              ARTICLE

P: To evaluate the efficacy of antiplaque, antigingivitis agents in studies involving six month randomized clinical trials.

M&M: Author searched studies on MEDLINE. Fifty studies were included. Because some of these studies compared multiple products with placebo groups, there were a total of 70 active groups in these studies. Two reports were unpublished reports that were identified to the plaque subcommittee formed by the FDA to evaluate over-the-counter agents, 13 were unpublished reports that were provided by manufacturers and 36 were published articles (nine of these studies also had unpublished research reports). Author abstracted the studies that met these criteria for outcome variables (PI, GI), sample size, blinding, randomization, agent types and formulations, and types of controls. Separate analyses of efficacy for each of the active agents was performed. A random-effects model was used to evaluate the overall efficacy of the data.

R: 17 studies support the antiplaque, antigingivitis effects of dentifrices containing 0.3% triclosan, 2% Gantrez copolymer. There was no evidence of efficacy for triclosan products containing either soluble pyrophosphate or zinc citrate. Dentifrices with stannous fluoride had statistically significant, but marginally clinically significant, evidence of an antiplaque effect; however, there was both a statistically and clinically significant antigingivitis effect. The largest body of studies (21 studies) supported the efficacy of mouth rinses with essential oils. A smaller body of studies (seven) supported a strong antiplaque, antigingivitis effect of mouth rinses with 0.12% chlorhexidine. Results for mouthrinses with cetylpyridinium chloride varied and depended on the product’s formula.

BL: Results suggest that for optimum gingival health, adults should add an antiplaque, antigingivitis agent to their oral hygiene regimen.

Chlorhexidine

 

Greenstein, 1986             ARTICLE

Background: At the time of this publication, CHX did not have FDA approval for intraoral use, was rumored to be carcinogenic, and there were claims that its use would lead to bacterial resistance.

Discussion: Chlorhexidine (CHX) was developed in the late 1940s as an antimalarial agent. Mechanism of action of CHX is that it is cationic in nature and acts to inhibit plaque by

1) Binding to anionic acid groups on salivary glycoproteins, and

2) Binding to salivary bacteria and interfering with their adsorption to teeth.

CHX is bactericidal in nature as it binds to cell walls and causes instability, and is effective against Gram (+), Gram (), and yeasts. Its antiplaque efficacy is due to its ability to adhere (substantivity) to anionic substrates (HA, pellicle, salivary GP, and mucous membranes). A key component is its substantivity; bound CHX remains intraorally and is released over an 8 to 12 hour period prolonging its bactericidal effect. It has a very low toxicity, mostly owing to its very low penetrance into oral tissues and little absorption in the GI tract.

Side effects include:

1) Staining of teeth and tongue,

2) Altered taste sensation.

3) Desquamative lesions in rare cases.

Its breakdown products include Parachloroaniline (PCA), an industrial chemical that is carcinogenic. To avoid this situation, the solution should be stored in a dark bottle and refrigerated. In long-term studies, no detrimental effects were found with chronic CHX use, however, bacteria were seen to be less sensitive after long term use but did not develop resistance. Rinsing, oral irrigation, and subgingival irrigation with CHX show positive effects in use and it has been shown superior to other antiplaque agents.

BL: CHX can be used as an adjunct to OH to aid in the control of gingival inflammation and plaque. It should not be used to substitute conventional OH measures, except in times of interrupted hygiene. Prophylactic longterm usage is inappropriate and is not recommended

 

Newman, 1989             ARTICLE

P: To determine the antimicrobial effect of 0.12% chlorhexidine mouth rinse on bacterial recolonization after periodontal surgery.

M&M: Study consisted of 40 patients investigated over 6 weeks. Patients with moderate periodontitis (Case Type III) underwent osseous surgery in one quadrant. Subgingival and marginal plaque samples were taken prior to surgery and at 2 and 6 weeks postop in that quadrant. Cultural analysis and assays for specific microbial populations were carried out.

R: During the 6 weeks of mouth rinse use, patients that used chlorhexidine had significant reductions over placebo in the following:

Gram positive facultative cocci – 85.8%

Gram positive facultative rods - (actinomyces) – 91.7%

Gram negative anaerobic rods – 94.5%

Capnocytophaga species – 97.6%

Few black pigmented bacteroides (Pg,Pi) or Aa were found prior to and after surgery. In the chlorhexidine group, 6 weeks post surgery; streptococci were the predominant bacterial group. Sig reduced in PI score (54%) during 6 weeks for CHx group compared over placebo.

C: The use of 0.12% chlorhexidine after surgery, sig reduced bacterial risk factors associated with gingival inflammation; wound healing during the 6 weeks of observation.

 

 

Quirynen, 2000              ARTICLE

P: To examine the relative importance of the use of chlorhexidine in the one stage full-mouth disinfection protocol.

M+M: 36 pts (all Caucasian, 37-69 yrs old, 16 F, 20 M) w/ chronic periodontitis. All subjects healthy, had at least 2 multi-rooted teeth and 3 single rooted teeth in first quadrant, with at least 6 sites having PD>7mm and with radiographic evidence of bone loss. Broken up into 3 groups: Control= SRP by quadrant, 4 sessions at 2 week intervals; FRp group= full mouth SRP w/in 24 hours; Fdis group= full mouth disinfection included full mouth SRP w/in 24 hours in combo with CHX. Clinical parameters (GI, Plaque w/ Quigley & Hein index, PDs, recession, CAL, and BOP) and plaque samples were taken from UR quadrant at baseline, 1, 2, 4, and 8 months later. Microbiological samples were taken from different intraoral sites (tongue, mucosa, saliva and pooled samples from single- and multirooted teeth), and were cultured on selective and non-selective media in order to evaluate the number of CFU/ml for key periodontopathogens.

R:

The 3 treatment options all resulted in significant improvements for all clinical parameters. The Fdis and FRp groups SS more results than the control group, with an additional PD reduction of 1.5 mm and an additional gain in attachment of 2 mm (for pockets>7 mm). Both the FRp and Fdis patients showed additional improvements when compared microbiologically to the control group, in the reduction of spirochetes and motile organisms as in the number of CFU/ml of the key-pathogens. The differences between FRp and Fdis patients were negligible.

BL: The data indicate that the one stage full-dentition SRP is the key factor to the additional clinical and microbiological improvements over a classical stepwise periodontal therapy. The adjunctive disinfection with chlorhexidine can be advisable since it offers additional effects in less complying patients, but it should not be considered mandatory as the FRp and Fdis groups had NSSD.

 

 

Zanatta 2007               ARTICLE

P: To compare the effects of 0.12 % CHX gluconate in plaque and gingival inflammation in sites with and without supragingival biofilm that was established in an experimental gingivitis model.

M&M: A single-masked, randomized split-mouth study using experimental gingivitis design including 20 individuals with PD<3mm who refrained from all mechanical plaque control methods for 25 days. To achieve optimal gingival health and to standardize gingival baseline conditions, all subjects participated in a 14-day pretrial period that consisted of professional scaling and polishing with a rubber cup and prophylactic paste and dental floss. On day 0(baseline), PI, GCF and GI were recorded in all subjects. After the recordings, a prophylaxis was performed and detailed explanations to stop all plaque control methods were provided. On day 4, each subject had one upper and one lower quadrant assigned randomly as tests (plaque-covered) and the other quadrants were the controls (plaque-free). Prophylaxis was given on control quadrants. On this day, all subjects continued the oral hygiene withdrawal for 21 days and started to rinse twice daily with 0.12% CHX gluconate. On days 11 and 18, the PI was recorded for all teeth. On day 25, PI, GCF and GI were recorded for all teeth. After the recordings, a prophylaxis was performed and all subjects were free to return to their normal habits of plaque control.

R: Intergroup comparisons showed statistically higher PI throughout the study on the plaque-covered surfaces compared to the plaque-free surfaces. In initially plaque-free quadrants mean GI values increased significantly from 0.180.01 to 0.520.03 on days 0 and 25 respectively. In initially plaque-covered quadrants, these values increased from 0.210.02 to 0.930.03 respectively, also statistically significant difference. When comparing GI between the 2 groups, at day 25, initially plaque-covered surfaces showed higher degree of inflammation. Both groups had a statistically significant increase in mean GCF from day 0 to 25(from 46.94 to 64.99 in plaque free surfaces and from 48.09 to 94.28 in plaque-covered surfaces).At day 25, a statistically significant difference was observed between the groups.

C: A 0.12% CHX gluconate mouthrinse had little antiplaque and antigingivitis effect on previously plaque-covered surfaces. Initially plaque-covered surfaces displayed greater amounts of plaque and gingival inflammation. Thus, professional removal of plaque is recommended before starting a CHX regimen as plaque-control substitute.

 

Faveri 2006             ARTICLE

P: To compare SRP vs SRP + CHX 0.12% rinse at 42 and 63 days after the completion of the SRP.

M&M: 30 pts with chronic periodontitis with at least one site that had a PD between 5 and 7mm and CAL between 5 and 10mm. Smokers and unhealthy pts were excluded. All study personnel were blinded to the tx and control group. Both groups received SRP and OHI. Pts were given a rinse, either CHX or placebo, and instructed to gargle for 1 minute, twice daily. Two periods of 3-day intervals were incorporated into the experimental phase in order to minimize the side effects of CHX, such as tooth-staining and unpleasant taste. All subjects were given the same toothpaste to utilize as well. Pts returned once a week to check compliance (empty rinse bottles). BANA test was used for T.f., T.d., and P.g. Sub-g samples were collected at baseline, after SRP, and at 42 and 63 days.

R: Although there were no differences in the clinical parameters between the two groups at baseline, the PI, BOP, PD and CALoss were significantly lower in the test group at 42 and 63 days than the control. The test group had a PI that was 30% better, BOP in 15% less sites, and about 1mm shallower PDs. There was a greater reduction in PDs, BOP, and improvement in CAL in the intermediate and deep sites. There were SS more sites that tested BANA positive in the control group vs the test group.

BL: The use of CHX as an adjunct to SRP can improve clinical parameters vs SRP alone.

 

 

Listerine

 

Cortelli 2009              ARTICLE

Purpose: to evaluate whether a mouth rinse containing essential oils would result in unaltered basic salivary parameters, while providing clinical or microbial benefits

Materials and methods

Results

Discussion

Bauroth 2003             ARTICLE

Purpose: To compare the efficacy of essential oil mouthrinse (Listerine) as compared to with that of dental floss.

Materials and methods:

Results:

 

Sharma 2004             ARTICLE

BG: Past studies suggested rinsing with Listerine was as good as flossing in controlling interproximal gingival inflammation.

P: to determine the incremental benefit of using an essential oil-, or EO-, containing mouthrinse in reducing plaque and gingivitis as an adjunct to brushing and flossing.

M&M: 6 month, randomized, controlled, examiner blind clinical trial. 246 pts w/ gingivitis were randomly assigned to one of three treatment groups: BC: brushing and rinsing with a control mouthrinse (negative control to see if mechanical action of rinsing improved gingival condition); BFC: brushing, flossing and rinsing with a control mouthrinse; or BFEO: brushing, flossing and rinsing with an EO-containing mouthrinse. Pts received a dental prophylaxis at baseline, and the authors followed them monthly for six months.

R: Of 246 enrolled subjects enrolled in the study, 237 subjects were evaluable at the study's conclusion. After six months, the subjects using both the BFEO and BFC regimens had statistically and clinically significant lower mean MGI and PI scores than did subjects in the BC group. The reduction in MGI and PI was statistically and clinically greater for BFEO regimen (29.9 percent and 56.3 percent, respectively; P < .001) than for BFC (11.2 percent and 9.3 percent, respectively; P < .001).

C: An EO-containing mouthrinse is an effective adjunct to regular brushing and flossing is beneficial for patients with gingival inflammation.

 

Stoeken 2007             ARTICLE

BG: Essential oil containing mouthrinses (EO) is an OTC mouthwash containing 2 phenol-related essential oils, thymol (0.064% and eucalyptol (0.092%), mixed with menthol (0.042%) and methyl salicylate 0.06% in a 22% hydro-alcoholic vehicle. At high concentrations of EO, there is disruption of the cell wall and precipitation of cell proteins. At lower concentrations there is inactivation of essential enzymes.

P: To review the literature on effects of a mouthrinses containing essential oils (EO) on plaque and parameters of gingival inflammation.

M&M: MEDLINE and Cochrane Trials searched up to Dec. 2006. Primary outcome measured was gingivitis, secondary parameters were plaque and staining.

R: Eleven out of 566 papers met search criteria. In all studies, EO was used as an adjunct to regular daily toothbrushing. A SSD reduction in gingivitis was noted compared to controls. SSD reduction in gingivitis when compared to control mouthrinse, but no difference when compared to floss. EO produced SSD reduction in plaque scores. For interproximal sites EO resulted in more pronounced plaque reduction compared to control or floss group. Most studies agreed that EO did not produce more staining than control group.

BL: When used as an adjunct to unsupervised oral hygiene, EO provides an additional benefit with regard to plaque and gingivitis reduction.

CR: 6/11 studies were funded by company. No information given regarding funding in other studies. 4 studies looked at flossing. Of those 2 that said EO was equivalent or better than floss were funded by industry. It was emphasized by the investigators of these studies that it is not the intention to replace flossing with a chemical rinse. But when approximal plaque control as practiced by the pt is insufficient, EO mouth rinse may be beneficial.

 

Ioannis 2013             NO ARTICLE

Purpose: To investigate the effect of commercially available mouthwashes on the survival and migratory capacity of human fibroblasts.

Materials and Methods: Human gingival and periodontal ligament (PDL) fibroblasts were treated with commercially available mouthwashes containing 0.12% chlorhexidine (CHX) or essential oils (EO) as the active ingredient.

Each mouthwash was tested over a range of concentrations for its ability to affect fibroblast survival and migration, as well as long- term effects on cell viability.

Results: 1-min exposure with dilutions of 1% CHX or 5% EO induced 50% bacterial cell death. Dilutions of 5% CHX and 15% EO induced >95% bacterial cell death. Concentrations >15% of either CHX or EO killed virtually all bacteria. Thus, diluted solutions of these mouthwashes significantly reduced bacterial survival. In contrast, dilutions <10% of either CHX or EO displayed no significant reduction in the viability of fibroblasts. When diluted to 10% to 15%, EO did not reduce cell migration, whereas similar dilutions of CHX resulted in reduced cell migration. <15% EO and <10% CHX did not induce membrane permeability nor- mally associated with cell death. Concentrations of 10% of both EO and CHX mouthwashes retained most of their antibacterial capacity. Treatment with EO did not result in gingival fibroblast death, whereas 5% CHX resulted in near-complete gingival fibroblast death 7 days after exposure.

Conclusion:

Triclosan

 

Rosling 1997             ARTICLE

Purpose: To examine if triclosan/copolymer incorporated in a dentrifice and used by perio patients could influence clinical parameters.

Materials and methods: 60 patients were selected from a group of patients recently treated for advanced periodontal disease. OHI and SRP were performed. The patients had during a 3-5 year period following active therapy been enrolled in a supportive periodontal therapy program (SPT), but had exhibited signs of recurrent periodontitis. The patients were split into 2 balanced groups with respect to mean probing depth. The test group included 30 individuals who used a dentrifice containing triclosan/copolymer/fluoride (0.3'%triclosan. 2% copolymer and 1100 ppm F from 0.243% sodium fluoride (Colgate Total).) while the control group used a similar dentrifice without the triclosan/copolymer. PD, BOP, CAL, were measured at the initial exam as well as radiographs taken. All pts received OHI initially and throughout the study. No subgingival therapy was performed over the 3-year period. Subjects were recalled every 3 months, and had re-examinations at 6,12,24, 36 months. Radiographs were performed again at the end of 3 years.

Results/Conclusion:

Test

Control

6mo

12

24

36

PD change

-.01

.02

-.04

.1

-.02

.16

-.14

CAL change

(loss)

.01

.18

.11

.21

.14

.35

.18

A meticulous, self-performed, supragingival plaque control maintained over a 3 year period failed to prevent recurrent periodontitis. In the test group, the daily use of triclosan reduced the frequency of deep periodontal pockets, and the number of sites that exhibited additional probing attachment and bone loss.

BL: Triclosan has antibacterial and anti-inflammatory properties

Cr: statistical sig vs clinical sig vs measuring error…

 

 

Rosling, 1997             ARTICLE

P: To evaluate the long-term effect on the subgingival microbiota of meticulous, self-performed, supragingival plaque control, and a triclosan/copolymer-containing dentifrice in adult subjects susceptible to destructive periodontitis.

M+M: 40 patients who received active nonsurgical therapy and were on maintenance for 3-5 years were included in this study. All of these patients had recurrent periodontitis. Six surfaces per tooth; BOP, PD, and probing attachment level (PAL) were recorded. The deepest pocket site in each quadrant (4 sites per subject) was selected and samples of the subgingival bacteria were taken. Two groups, Test group: triclosan/copolymer, Control group: with the same toothpaste but without triclosan/copolymer. Subjects were recalled every 3 months for OHI and correction if needed. Subjects were then re-evaluated at 36 months. No professional subgingival therapy was delivered between the baseline and 36-month examinations. Subjects were blinded to which toothpaste they were using.

R: Changes in PD for test was -0.4 mm and for control +0.1 mm, Significant reduction in viable bacteria in both control and test but SS more in test group, this was most obvious with regards to PI.

BL: Triclosan/copolymer prevents recurrence and disease progression. Meticulous OH alone is not enough to stop disease progression.

 

Medicaments - Fluorides

 

Ciancio 1992             ARTICLE

P: To determine the effect of a stannous fluoride containing mouth rinse on existing and developing dental plaque.

M+M: 55 healthy adults (mean age=31 years old) received prophy in randomly assigned contralteral quadrants and were placed into two groups. One group, control, used placebo rinse and second group, experimental, used the 0.1% stannous fluoride rinse. Plaque index and stain index were evaluated at baseline, 1 and 3 weeks. Both groups used a new soft toothbrush and a low abrasive toothpaste. Total duration of the study was 3 weeks.

R: Experiment group

Plaque reduction wk 1

Plaque reduction wk 3

Prophy quadrants

21%

28.4%

No prophy quadrants

20.8%

29.2%

Stannous fluoride group had statistically significant plaque reduction after 1 and 3 weeks when booth prophied and unprophied sites were compared to the placebo. There was no significant difference between the stannous fluoride and placebo group for the stain index.

BL: Rinsing with the stannous fluoride solution along with brushing significantly reduces plaque. It was effective at preventing new plaque accumulation as well as reducing existent plaque. Slight teeth staining were observed in the experimental group but it wasn’t significant.

 

Bacca 1997             ARTICLE

P: To compare the antimicrobial activity of four commercial oral products: 1) conventional NaF dentifrice (Crest) 2) baking soda/peroxide/NaF dentifrice (Mentadent) 3) essential oil mouthrinse (Listerine) and 4) SnF2 dentifrice (Crest plus Gum Care).

M&M: TEST 1: 30-hour dental plaque regrowth assessment (six 30-hour cycles). 43 systemically healthy individuals participated in the study. Under supervision they rinsed with one of the six treatments, three times during each of six 30-hour cycles: 1) purified water 2) Crest regular dentifrice 3) Mentadent Baking Soda and Peroxide Toothpaste 4) Crest plus Gum Care dentifrice 5) Listerine mouthwash and 6) an experimental dentifrice. The dentrifices were used to prepare a 25% dentrific/water slurry. The study was completed over a 7-week period. Plaque was determined following fluorescent staining. Formulations were compared for their ability to decrease dental plaque following toothbrushing, during thirty hours of non-brushing where products were used as oral rinses (30-hour plaque regrowth model). TEST 2: General surface microbial index (GSMI) is a method, designed to assess the effectiveness of formulations in reducing bacterial populations of facultative anaerobic bacteria on gingival surfaces following product use.15-20 subjects participated in 2 separate studies. A) The patients brushed with 1) Crest regular dentifrice, 2) Crest plus Gum Care dentifrice, 3) Mentadent. B) The patients brushed with 1) Crest regular dentifrice, 2) Crest plus Gum Care dentifrice, 3) Crest Gum Care gel dentifrice, 4) Mentadent. Following toothbrushing, gingival surfaces were swabbed at timed intervals, permitting an assessment of both the magnitude of the initial effects in reducing bacterial populations and length of time where viable bacterial counts on these surfaces are suppressed. The formulations were compared for their ability to decrease the colony-forming units (cfu) of facultative anaerobic bacteria sampled from buccal gingival surfaces following product use. TEST 3: Plaque glycosis and regrowth method (PGRM) permits the direct measurement of antimicrobial activity of oral products applied in vivo. 8 subjects, 2 groups for evaluation of 1) Crest plus Gum Care dentifrice, 2) Crest regular, 3) Mentadent. These were compared for effects in suppressing the glycolytic metabolic activity and regrowth activity of in vivo-treated dental plaque sampled at 15 and 45 minutes following topical product use.

R: TEST 1: In 30-hour plaque regrowth testing the rank ordered antimicrobial efficacy of formulations followed SnF2 >essential oils> NaF=water=baking soda/peroxide. There was almost no plaque regrowth in the SnF2 group at 30 hours. TEST 2: In GSMI testing, all formulations were shown to suppress the cfu of facultative anaerobic bacteria relative to baseline, although SnF2 treatment reduced bacterial levels to a significantly greater degree than NaF dentifrice or baking soda/peroxide dentifrice up to 2 hours following toothbrushing. TEST 3: In PGRM testing the SnF2 dentifrice provided significant inhibition of bacterial metabolism and regrowth following topical application when compared with the NaF dentifrice (as control). The baking soda/peroxide dentifrice provided no reduction in either bacterial metabolism or regrowth in PGRM. These results demonstrate that SnF2 dentifrice provides substantial intraoral antimicrobial effects. The essential oil mouthrinse also exhibits significant intraoral antimicrobial effects. The baking soda/peroxide dentifrice did not produce any antimicrobial effects following in vivo use compared with conventional dentifrice.
BL: The results showed that SnF2 and essential oil formulations can be used in reducing gingivitis, while providing no support for the expectation of clinical efficacy for formulations containing baking soda and perioxide.

 

Miscellaneous Compounds

 

Caton JG 1993              ARTICLE

Purpose: The aim of the study was to compare the effect of mechanical cleaning regimen and a chemical plaque control regimen on the prevention and txt of interdental gingival inflammation.

Materials and methods:

92 healthy male subjects, age 18-28 y, w/at least 8 IPX bleeding sites.

Eastman interdental bleeding index used at baseline then monthly for 3 months.

All had prophy and OHI prior to baseline. 3 groups: 34 subjects in mouthrinse group: rinse w/0.12% CHX plus toothbrushing (no IPx mechanical cleaning), 32 subjects in mechanical group: toothbrushing w/soft wooden toothpick to mechanically clean IPx and 26 control subjects who were not given OHI and instructed to continue normal home care.

Results:

Van der Weijden 1998              ARTICLE

Background: In 1989 a patent has been filed at the European Patent Office, which states that the combination of an Urtica dioca extract and a Junipereus communis extract leads to a synergistic reduction of both dental plaque and bleeding of the gingiva. A further improvement may be obtained by adding an Achillea millefolium extract

Purpose: To establish in vitro the inhibiting effect of these 3 herbal extracts on a selected numbers of micro – organisms and to test in vivo the effect of the mouthwash containing this herbal extracts mixture on gingivitis as compared to a minus active control mouthrinse.

Materials and methods:

Results:

Conclusion: The combination of the 3 herbal extracts when used in a mouthrinse has no clinically measurable effect on plaque growth and gingival health.

 

Greenstein 1999             ARTICLE

P: To review the literature concerning the effects of povidone-iodine (PVP-I) and its potential use to treat perio dz.

D: Povidone-Iodine is a solubilized form of iodine that reduces irritability and decreases staining caused by pure iodine. It is a microcidal agent for gram + and gram -, fungi, mycobacteria, viruses and protozoans.

Arweiler 2001             ARTICLE
P: To assess the plaque inhibitory properties and the effect on plaque vitality of four alcohol-free mouthrinse formulations, an amine fluoride/stannous fluoride mouthrinse (ASF) and two triclosan solutions in comparison with a chlorhexidine and compared to a placebo.

M&M: Double blind, randomised 5-crossover 4-day plaque regrowth study was performed on 19 pts (10 M and 9F). One test formulation contained ASF with 250 ppm fluoride, two others were triclosan solutions of different concentrations (0.02% and 0.15%), whereby the 0.02% triclosan preparations also contained 0.1% allantoin. Additionally a negative control (placebo, water with flavoring) and an alcohol-free chlorhexidine (0.1%) were used. All 5-test preparations were without ethanol. Every test cycle was followed by a 10d washout period. On 0 d of each test, pts received a prophy. Thereafter they refrained from all mechical OH procedures for the next 4d. Plaque area was evaluated only at the last day (day 4) of each test week after staining the plaque covering the buccal surfaces of upper and lower incisors and canines with erythrosine (1%) and photographing. The vitality of the plaque was examined on days 1 to 4 by the vital fluorescence technique.
R:

BL: Alcohol-free mouthrinse solutions were shown to be effective in reducing both plaque accumulation and plaque biofilm vitality compared to a placebo solution.

 

Sreenivasan 2002             ARTICLE

Purpose: A review article on antiplaque biocides and bacterial resistance

Discussion: Long-term use of oral care formulations with well-known antiplaque biocides such as CHX and triclosan reduces supragingival plaque and gingivitis.

No adverse alterations in the bacteria found in dental plaque or emergent microbial resistance.

No increase in resistant microflora. Large numbers of common oral bacteria isolated from patients using CHX indicate no increase in microbial resistance to CHX or commonly used antibiotics (Amoxicillin, penicillin, tetracycline, etc)

Formulations containing in biocide: surfactants (has anti-nucleating agent which prevent mineralization of soft plaque), polymers and other components are effective against the biofilm.

Repeated use of hand disinfection by dental health personnel under real life conditions did not result in emergence of resistant bacteria.

BL: Use of oral care formulations with antiplaque biocides shows no emergence of resistant microflora, or alteration of oral microbiota, while such formulations have been found to provide benefits of reducing plaque and gingivitis.

** Biocides mentioned in this review (no one caused bacterial resistance)

- Dentifrices: Triclosan, EO, SnF2, CHX

- Mouthrinses: CHX, PVP-I/H2O2, EO, SnF2

Biocide

Mode of Action

Typical use

CHX

Loss of structural organization, membrane damage, congealing of cytoplasm at high concentrations

Mouth rinse, oral spray, hand disinfectant

Triclosan

Membrane damage, release of cellular components

Dentifrice, hand soap, liquid soap

Cetylpyridinium chloride

General membrane damage

Mouth rinse, hand disinfectant

Phenolic flavors

Protein denaturation, cell membrane damage

Mouth rinse, lozenges, chewing gum

Metals (Zinc, Stannous)

Binding of -SH (thiol) groups

Dentifrice, mouth rinse, chewing gum

Detergents (e.g. sodium dodecyl sulphate)

Structural/functional changes, initiation of autolysis

Foaming agent, detergent

Povidine iodine

Binding of -SH (thiol) groups

Hand disinfectant, oral irrigant

 

 

Comparative studies

 

Wennstrom & Lindhe 1986             ARTICLE

P: To assess the efficacy of mouthwashes containing antiseptic agents using a new research

M&M: 21 patients (33-48 y/o) with periodontal disease were examined for baseline PI, GI, BOP and PD’s. They were randomly assigned to 1 of 3 groups. Group A rinsed with 0.01% Sanguinarine (a quaternary ammonium salt extracted from bloodroot- hence the name), group B with 0.2% CHX and group C with a placebo solution. Study lasted 6 weeks. After 2 weeks of rinsing, re-examination & SRP was done in 2 quadrants; after another 2 weeks the other 2 quadrants were re-examined and scaled. Final examination was 2 weeks later (6 weeks from baseline). No instruction regarding mechanical plaque removal was given to any group.

R: During the 4 weeks of rinsing (without SRP) PI was significantly reduced in both the Sanguinarine (38%) and CHX (82%) groups; with no difference in the placebo group. GI and PD were not significantly affected in any group. The professional debridement markedly reduced the signs of gingivitis. Frequency of GI scores 2 &3 reduced by 55% in the Sanguinarine group, by 63% in the CHX group and by 35% in the placebo group.

BL: CHX & (to a somewhat less extent) Sanguinarine, were used as supplements to routine oral hygiene, with gingivitis resolution beyond that of the placebo group. The 2 antimicrobial mouthwashes were effective on supragingival but not on established subgingival plaque, (since there was no effect on BOP for quads that were not scaled). SRP reduced GI and PD in all groups.

Axelsson 1987              ARTICLE

P: To determine the clinical effect of two chlorhexidine digluconate solutions and listerine used as mouthwashes to supplement regular oral hygiene measures on dental plaque and gingivitis in humans.

M+M: 96 subjects, 16-50 years old, all had signs of varying degrees of gingivitis but no periodontitis. Following baseline exam, each subject given prophy. All subjects were assigned either to 1 of 3 different treatment groups or to a control group. The members of the control group and the Listerine group rinsed with 20 ml of the mouth rinse for 30 seconds two times a day, while the members of the chlorhexidine groups (0.2% or 0.1%) rinsed with 10 ml of the antiseptic solution for 60 seconds 2x/day. GI score, plaque score w/ Quigley-Hein Index (0-5), extrinsic stain w/Lobene index (scored for both area covered and severity (0-3) obtained at baseline and at 6 weeks.

R: The three active mouthwash preparations used as supplements to regular tooth cleaning measures improved both the OH status and the gingival conditions of the subjects, compared to the control rinse. The degree of improvement was more pronounced on the incisors than on the molars.

BL: All three active mouthwashes preparations were effective in reducing plaque and signs of gingivitis in patients who continue with their regular teeth cleaning habits. The chlorhexidine-containing groups were equally or more effective in reducing plaque.

 

Grossman 1989             ARTICLE

P: To compare CHX 0.12%, phenolic compounds and sanguinarine in a 6-month study with respect to their ability to control plaque, gingival inflammation and BOP.

M&M: 481 people with at least 16 teeth and one gingival site that had BOP were included. Subjects received a prophylaxis at baseline and were examined for gingivitis, plaque, oral soft tissue status and stain (photographs). The examinations were repeated at 3 and 6 months. Pt were assigned to one of four groups: CHX (Peridex), phenolic essential oils (Listerine), sanguinarine (Viadent), placebo (Peridex without clorhexidine gluconate). Subjects were instructed to use the mouthrinses in accordance to the manufacturer’s instructions. A sodium fluoride dentifrice (Crest) and soft toothbrushes were given to the pt and they were told to use them according to their individual habits.

R: All products significantly reduced plaque levels compared to the placebo group at 3 and 6 months. CHX was significantly more effective at plaque than Listerine, which in turn was significantly more effective than sanguinarine. Reductions in gingival inflammation and BOP were only seen to be significant in the CHX group at 3 and 6 months. The Listerine group was statistically better than the placebo group at 3 months in reducing gingivitis. CHX had a 38.8% reduction in BOP at 6 months, over twice the amount of any other group. At 3 and 6 months, the CHX and phenolic compound groups displayed significantly more intrinsic staining (more the CHX group) than the other 2 groups.

BL: CHX is superior in maintaining gingival health after 6 months in comparison to sanguinarine and phenolic compounds, although it also produces the most amount of staining.

 

Gultz 1998             NO ARTICLE
P: The purpose of this in vivo study was to determine and compare the antimicrobial effectiveness of three commercial mouthrinses (Listerine, Peridex, and Herbal Mouth and Gum rinse) and a water control.
M/M: The antimicrobial efficacy of the products was determined against aerobic, micro-aerophilic, and anaerobic bacteria. 20 subjects included. Each subject used the mouthrinses randomly in a series of 4 experimental sessions, which were separated by at least 1- days, whith each subject serving as his/her control. A pre-test saliva sample was taken after rinsing with distilled water and then chewing paraffin wax for 1 minute to displace plaque. This sample was divided and used to grow three bacteria cultures. After giving the pre-test sample, the subject rinsed with one of the mouthrinses or the water control for 30 seconds, then waited one hour, at which time a post-test saliva sample was collected (they were told not to put anything in their mouth during that hour). Again, the sample was divided and used to culture the different types of bacteria. Following a 48-hour incubation period, the numbers of microbial colonies on each plate were counted and compared.
R/BL: All of the mouthrinses performed significantly better than the water control at inhibiting aerobic, micro-aerophilic and anaerobic bacteria; however, Herbal Mouth and Gum Therapy and Peridex were both significantly more effective than Listerine in inhibiting all bacteria, with NSD between the Herbal Mouth and Gum Therapy and Peridex.

Cr: Results only for 2 hours after rinse (1 hour for plaque to accumulate after rinse, and 1 hour of cultivating before taking measurements)

 

Pan 1999             ARTICLE
Purpose:To investigate the bactericidal activity of Listerine (Essential Oil EO), Meridol (Stannous Fluoride SF), and water (C).
Materials and methods:

Results:

 

Antibiotics Review of Concept

 

Slots 2001             ARTICLE

Purpose: To evaluate the utility of systemic AB’s in the TX of moderate to severe types of periodontitis and of some special clinical situations and to makes recommendations for therapy.

Discussion: Mechanical treatment of periodontitis may fail to remove pathogenic organisms because of their location in subepithelial gingival tissue, crevicular epithelial cells, altered cementum, calculus, furcations or other anatomic features. Periodontal pathogens also colonize oral mucosa, tongue dorsum, tonsils and other oral domains and may translocate from non-periodontal sites to periodontal crevices. Systemic antibiotics enter the tissues and can potentially suppress periodontal pathogens residing in these sites.

To maintain effective antimicrobial levels after oral administration penicillins and clindamycin must be taken three times a day, metronidazole, ciprofloxacin and erythromycin twice a day and doxycycline and azithromycin once a day.

A recent study by Sakellari showed that the average concentration of systemically administered concentrations in GCF in lower than in the plasma and varies significantly among individuals possibly explaining much of the variability in clinical response.

Adverse reactions, cost, interactions are factors that should be considered.

Systemic antibiotics do not significantly affect supra-g plaque. Systemic antibiotics might not have significant effect on gingival inflammation with the possible exception of metronidazole.

They don’t have impact on PD compared to controls with the exception of amoxicillin combined with metronidazole.

Systemic antibiotic therapy can improve radiographic alveolar level and other periodontal variables, can have a beneficial effect on periodontal disease activity and reduce the need for surgery as determined by a periodontists having no knowledge of the therapy rendered.

Many antibiotic therapies are unable to suppress subgingival Aa, metronidazole or tetracycline may be able to reduce A.a. but not eradicate it especially serotype b which seems to be more resistant. Periodontal surgeries may help towards this direction especially in combination with these antibiotics.

Combination of metronidazole (250mg) and amoxicillin (350mg) three times/day comprises and effective and low cost therapy against Aa in patients with aggressive or refractory periodontitis and Papillon – Lefevre syndrome periodontitis but dentists should not only rely on antibiotics for eradicating Aa.

Predictable and long-term eradication of P. gingivalis from deep periodontal sites requires a combination of systemic antibiotic therapy, SRP, surgeries and professional and self-care administration of subgingival antiseptics.

Tetracyclines seem to be more effective against subgingival spirochetes.

In addition to reducing levels of periodontopathogenic bacteria systemic antibiotic therapy may lead to increased levels of antibiotic-resistant innocent or beneficial bacteria as streptococci or Actinomyces.

A conservative and highly selective approach is recommended for periodontal antibiotic therapy.

Indiscriminate therapy may lead to increase resistance to antimicrobial agents that are valuable in potentially fatal medical infections.

If microbiological test is unavailable, metronidazole-amoxicillin combination may be a reasonable antibiotic first choice in periodontics. Metronidazole and ciprofloxacin (500mg each, twice daily for 8 days) is another valuable therapy that cures anaerobic, enteric rod and Aa periodontal infections and promotes sub-g overgrowth of streptococci available to inhibit Gram- pathogens.

The use of antibiotic therapy in patients with aggressive periodontitis or NUG can give very good results, while the use in chronic periodontitis is not that clear yet.

 

Walker 2002              ARTICLE

D: The purpose of this review is to provide the clinician with some practical rationale for the selection and use of antibiotics in the treatment of periodontal disease. Based on the evidence that is available, the following conclusions are drawn. Adjunctive use of antibiotics along with mechanical debridement is recommended for the treatment of Aa-associated periodontitis. Due to the emergence of tetracycline resistance Aa, the combination of metronidazole and amoxicillin may be preferable. In aggressive refractory periodontitis, compelling evidence exists that the use of an appropriate adjunctive antibiotic frequently gives a more favorable clinical response than mechanical therapy alone. Unfortunately, the selection of antibiotic is not as clear and is probably case dependent. Positive response has been shown with amoxicillin/ Clavulanic acid, clindamycin, metronidazole, metro plus amoxicillin.

 

Haffajee 2003             ARTICLE

P: Systematic review to determine whether systemically administered antibiotics improve a primary clinical outcome measure, periodontal attachment level change.

M&M: PubMed searched from 1966 to 2002, only human studies in English

R/BL:

Listgarten 2003             ARTICLE

Purpose: To determine whether microbial identification affects patient management and whether treatment outcomes are better than that of patients treated without that information.

Discussion: 13 articles were selected, only one controlled trial, 38 patients treated by test periodontists (they modified 69% of the treatment plan due to microbial identification results), and 48 patients treated by the control periodontist who did not utilize microbial identification.

Bacteria tested included A.a. P.i. T.f. P.g. C. rectus, spirochetes and motile rods were also monitored, modifications of treatment included 45% more appointments, 46% more SRP sessions, and 79% more courses of antibiotics, however, patients in the control group received more surgeries. There were no reports on the effect of treatment.

Publications on effect on treatment are mostly case reports and case series.

BL: Microbiological monitoring may be useful in management of selected patients who do not respond to standard therapy, lack of evidence on treatment outcomes doesn’t necessary mean there is no benefit, further research is needed.

 

AAP 2004 position Paper: Systemic antibiotics in Periodontics             ARTICLE

D: Antibiotics may be prescribed for periodontal patients who do not respond to conventional mechanical therapy, for acute periodontal infections associated with systemic manifestations, for prophylaxis in medically compromised patients, and as an adjunct to surgical and non-surgical periodontal therapy.

Patient selection – The best candidates:

Clinical Studies- Most studies concerned with patients with disease progression suggest that properly selected systemic Abs may provide significant additional clinical benefit to conventional mechanical periodontal therapy, especially in patients with recurrent or refractory periodontitis. Abs are very valuable in treatment of aggressive periodontitis in adolescents, especially cases predominated with AA.

Microbiological analysis- Dentist is encouraged to know pathogenic microbial content of the subgingival microbiota in order to avoid prescribing inappropriate antimicrobial agents that are resistant to treatment. Testing is ideally done following mechanical therapy and then 1-3 months after antimicrobial therapy. Sampling is done with a paper point or a curet. Samples should be placed in appropriate transport mediums in order to sustain viability of sampled organisms if needed. Culture methods are good at determining viable cell counts and presence of pathogens but are highly technique sensitive, expensive and are unable to grow some organisms. Non culture methods such as a DNA probe and polymerase chain reaction (PCR) assays do not require live cells and have a high sensitivity and specificity, however, only a limited number of species can be detected.

Antibiotic selection

Metronidazole- May arrest disease progression in recalcitrant periodontitis patients with Porphyromonas gingivalis (PG) and/or Prevotella intermedia (PI). Can attain effective antibacterial concentrations in the gingival tissues and GCF. Cleared by hepatic metabolism (6-14 hour half life), and half life unchanged with renal dysfunction.

Clindamycin- Efficacy in recurrent periodontitis and works well against gram (–) anaerobic rods and Peptostreptococcus or B-hemolytic streptococci. Caution of psuedomembranous colitis.

Tetracyclines – Effective when AA is prominent pathogen but may not be effective with mixed infections. GCF concentrations mat not be as high as previously thought. May inhibit gingival collagenases. Contraindicated during pregnancy and for children younger than 8 years old.

Fluoroquinolones- Effective against enteric rods, psuedomonads, staphylococci, and AA. Penetrates readily into diseased periodontal tissues and GCF. May induce tendinopathy and strenuous exercises should be avoided while taking this medication.

Azthromycin- Has excellent ability to penetrate both normal and pathologic periodontal tissues.

Metronidazol + Amoxacillin or Metronidazol + Ciprofloxin - Predictable eradication of AA and marked suppression of Porphyromonas gingivalis (PG).

Common antibiotic therapies in the treatment of periodontitis

 

Antibiotics- Rationale

Ehmke 2005            ARTICLE

P: To evaluate the long-term effects of adjunctive antimicrobial therapy on periodontal disease progression and oral colonization.

M+M: 35 patients with untreated moderate to severe chronic periodontitis and subgingival infection with A. actinomycetemcomitans and/or P.gingivalis participated in a 24-month study. At baseline, patients were randomly assigned to supragingival and subgingival scaling w/ OHI alone (control group) or in combination with an 8-day adjunctive antimicrobial regime (systemic administration of metronidazole 250mg t.i.d., amoxicillin 375mg t.i.d. and supragingival irrigation with 0.06% chlorhexidine digluconate once daily). The adjunctive antimicrobial therapy was started immediately after completion of scaling. CAL and BOP were assessed at baseline, 3,6,9,12,18 and 24 months and microbiological plaque samples were taken at baseline before scaling, 10 days, 3,6,9,12 and 24 months after completion of therapy. All patients received maintenance therapy consisting of full-mouth supragingival debridement at 3,6,9,12,18 and 24 months.

R:

A reduction in BOP of 9.6% in the test group and of 8% in the control group was recorded at 24 months irrespective of initial PD.

At sites with an initial PD of 7mm or more, scaling plus antimicrobial therapy compared to scaling alone led to a SS higher proportion of sites gaining attachment and to SS lower proportions of sites losing attachment.

Sites with an initial PD of 0-3mm and 4-6mm, the proportions of sites with attachment gain or loss of 2mm was NSSD between the groups.

With the exception of Aa, no long-term eradication of periodontal pathogens from the oral cavity was registered over the entire study period.

Compared to controls the prevalence of Aa in the test group SS decrease from 3 through 18 months and the prevalence of Pg SS decreased from 10 days to 3 months.

The prevalence of E. corrodens in subgingival increased 10 days after adjunctive antimicrobial therapy but returned to baseline detection frequency at 3 months.

In both groups, a transient decrease in T. forsythensis was recorded, while the detection frequency of Treponema ssp increased.

BL: Compared to controls, adjunctive antimicrobial therapy led to a significantly reduced intraoral prevalence of Aa for up to 18 months, but to only transient changes in the prevalence of P. gingivalis and E.corrodens. Scaling plus antimicrobial therapy resulted in a significant reduction in the percentage of sites showing an attachment loss of 2mm at sites with an initial probing depth of 7mm. The performed antimicrobial therapy may be considered as an adjunct to mechanical debridement in patients with moderate to severe chronic periodontitis.

 

Haffajee 2007            ARTICLE

P: To compare clinical changes in chronic periodontitis patients receiving SRP alone or with systemically administered azithromycin, metronidazole, or a sub-anti-microbial dose of doxycycline.

M&M: 98 patients from different ethnicities with at least 20 teeth and at least 8 sites with PD > 4mm were recruited. The 4 groups were SRP alone, SRP + Azithromycin 500mg once for 3 days, SRP + Metronidazole 250mg t.i.d. for 14 days, and SRP + sub-antimicrobial dose doxycycline b.i.d. for 12 weeks. Subjects were monitored at baseline, 3, 6, and 12 months post-therapy. In addition, all subjects received maintenance SRP at the three post-therapy monitoring visits. At these visits, BOP, overt gingivitis, suppuration, PPD and PAL were measured at 6 sites per tooth.

R: 92 patients completed the study, but only 67 of them had complete data for all 4 monitoring visits. There were 16 pt with 1 missing visit and 9 pt with 2 missing visits; their data from the last observation was carried forward. There were significant improvements for most parameters in the study, especially from baseline to 3 months. In general, subjects receiving adjunctive agents exhibited greater clinical improvements than SRP alone, especially for PD and AL. The data analyses were repeated for mean PD and AL change at sites with BPDs > 6mm. All groups showed significant improvements. Those who received AZ or MET showed greater mean PD reduction post-therapy compared with subjects in the SDD and SRP only groups. These differences were statistically significant at 6 and 12 months. In the AZ group, 12% (3 pt) showed an increase in PD at 12 months, while this was the case in 15-22% of pt in the other groups. 39% of subjects had clinical attachment loss at 12 months in the SRP group, more than twice the proportion in the SDD and MET groups. The AZ group exhibited the largest amount of sites with attachment gain > 2mm (5.3%), and the MET group showed the lowest % of sites showing attachment loss (0.41%). All groups exhibited a greater % of sites gaining attachment than losing attachment > 2mm. Little difference was observed between sites with BPD < 5mm.

BL: SRP + adjunctive therapy is more beneficial in PD > 6mm than SRP alone.

 

Antibiotic-Resistance

 

Walker 1996            ARTICLE

P: review article on acquisition of antibiotic resistance in the periodontal microflora.

D: several articles looking at antibiotic resistance reviewed by authors

Antibiotics-Combination therapy

 

Matarazzo 2008            ARTICLE

Purpose: To evaluate the clinical and microbiological effects of SRP alone or combined with metronidazole (MTZ) or with MTZ and amoxicillin (AMX) in treatment of smokers with chronic periodontitis.

Materials and methods:

Results:

Lopez 2006            ARTICLE

Purpose: To evaluate the changes in proportions of 40 bacterial species in untreated chronic periodontitis patients after the administration of metronidazole amoxicillin as the only therapy.

Materials and methods: 22 subjects, 15 women and 7 men, over 38-68 years old with chronic periodontitis. They had received no periodontal therapy and no personal instruction to prevent periodontal disease. Systemically healthy patients, at least 18 teeth and at least six PDs of 4mm or more. Radiographic evidence of moderate to advanced periodontitis should be present.

Before the onset of the study each patient received supragingival scaling to remove calculus and allow probing.

The following variables were determined at the beginning of the study and every 3 months up to 1 year post-therapy: plaque score, gingival inflammations, PD and AL at six sites per tooth and patients were also microbiologically monitored by taking subgingival plaque samples from the mesial aspect of all teeth and received supra gingival scaling.

Control group received SRP and placebo A and B tablets while test group metronidazole 250mg and amoxicillin 500mg every 8h for 7 days. OHI instructions were given to the patients. At the beginning of the study and at each monitoring visit, each subject was provided with three toothbrushes and toothpaste.

Results: No subject experienced any adverse side effect. Test group had significantly higher BOP and PD 4-6mm than test group at baseline.

Reduction of spirochetes in plaque samples of the test group showed that all of them had good compliance with the prescribed medication.

There was a statistically significant reduction over time in the mean PD, AL and BOP for both groups. Test group showed 0.3mm of AL gain and control group 0.17mm. PD reduction was also higher in the test group.

The majority of bacterial species showed reduction during the study in both groups with the highest reduction being observed between baseline and 3 months. At 12 months many of the species were still present in significantly lowered levels (even for members of the red complex) compared with their baseline counts in both groups, with similar pattern overall between them.

Conclusion: 1) Systemically administrated antibiotics provided clinical and microbiological improvements similar to those observed as a result of SRP alone, which is not in accord with the notion that it is essential to mechanically disupt the biofilms.

2) Reduction in the counts of subgingival species resulted in clinical improvement and it didn’t matter whether the reduction was because of mechanical debridement or antibiotics.

 

Antibiotics-Tetracycline

 

Sakellari 2000            ARTICLE

P: To measure concentrations of 3 tetracyclines in gingival crevice fluid (GCF), plasma and saliva of following systemic administration.

M&M: The concentration of tetracycline (TC), minocycline (MN) and doxycycline (DX) was measured in gingival crevice fluid (GCF), plasma and saliva of 20 subjects following single sequential standard oral systemic doses. Gingival crevice fluid concentration was measured at 4 sites (2 shallow and 2 deep) before administration, and at 1 h and 2 h following administration. Plasma and saliva concentrations were measured from in samples at the same time points. No antibacterial activity was detected before administration. The highest concentrations were measured 2 h after administration.

R: The average concentrations at 2 h were highest in plasma (TC = 1.02, MN=2.18, DX=2.35 microg/ml). Intermediate concentrations were measured in GCF (TC=0.61, MN= 1.49, DX= 1.65 microg/ml). Saliva concentrations (TC=0.09 MN=0.31, DX=0.47 microg/ml) were the lowest of the 3 fluids monitored. Data are presented indicating that the average GCF concentration of systemically administered tetracyclines is less than the that of plasma concentration. The concentration of tetracyclines in GCF was strongly associated with plasma concentration, indicating a primary role of drug absorption in the delivery of these systemically administered antibiotics to the site of action in periodontal therapy. The average GCF concentration in individuals varied widely (between 0 and 8 microg/ml) with approximately 50% of samples not achieving levels of 1 microg/ml.

C: These observations suggest that poor absorption of orally-administered tetracyclines in many individuals may account for much of the variability in clinical response to antibiotics observed in practice.

 

Rodrigues 2004            ARTICLE

P: To evaluate longitudinally the tetracycline resistance patterns of the subgingival microbiota of periodontitis subjects treated with systemic or local tetracycline therapy+SRP

M&M: 30 chronic periodontitis pts. All subjects with at least 20 teeth and 4 sites with PPD > 6 mm at baseline. No subjects used antiobiotics 6 months prior to the study. Clinical measurements included PPD, CAL, BOP, PI at baseline, 3, 6, and 12 months. 3 groups: 1) FM SRP+systemic tetracycline (500 mg 1x2 for 14 days); 2) FM SRP only; 3) FM SRP+local placement tetracycline (Actisite). All pts received SPT without subgingival interventions. Microbiological assessment performed in selected 4 non-adjacent sites with PPD ranging from 6-10 mm using subgingival plaque samples.

R:

D/BL: Local and systemic tetracycline therapy combined with SRP results in an initial transient increase in the percent of resistant microorganisms. The high prevalence of resistant periodontal pathogens prior to treatment in this population suggest that this agent should be considered carefully and restricted to patients who do not respond to conventional therapy or present a more aggressive disease. Nevertheless, both therapies resulted in a decrease of the prevalence of resistant suspected periodontal pathogens over time.

 

Ramberg 2001            ARTICLE

Purpose: To evaluate both the short and the long- term effect of a treatment protocol that included administration of systemic tetracycline and non-surgical intervention during the phase of basic therapy.

Material and Methods: 35 adult human subjects with advanced periodontitis (19F and 16M), 24-60 yrs, were included in a test group. Control (n=80). A baseline examination included assessment of the following parameters: # teeth, plaque, BOP, PAL, PD. In radiographs, the distance between the CEJ and the alveolar bone crest was determined
at all IP sites. OHI given.

Test group: were provided with tablets with 250 mg of tetracycline hydrochloride and were instructed to take 1 tablet 4x per day for 3 weeks. No antibiotic was given to the subjects in the control group. During the 3-week interval, all participants received 4–6 sessions of non-surgical periodontal therapy. All subjects were subsequently enrolled in a maintenance care program and were provided with SPT 3–4 x per year. Clinical re-examinations were performed after 1, 3, 5 and 13 years.

Results:

 

At the re-examination 1 year after active therapy, there was in the test group an average gain in PAL that was almost 3 times higher than the gain that occurred in an age and sex matched. Control group. Re-examinations after 3, 5, and 13 years of SPT disclosed that this short- term benefit was not maintained in the longer perspective.

 

 

Conclusion: The beneficial effect of systemically administered tetracycline is only short term.

Macrolides

 

Mascarenhas 2005            ARTICLE

 

P: to evaluate concommitant use of azithromycin in conjuction w. SRP vs SRP alone for initial therapy in smokers .

M/M: 31 patients examined over 6 months had microbial samples and GCF evaluated for ICTP (pyridinoline cross-linked carboxyterminal telopeptide of type 1 colagen). Patients had to smoke >/= 1pack per day with at least five sites of 5mm PD w/ BOP. SRP was performed and 15 patients received azithromycin 250mg, 2 first day and 1 for four days afterward. 16 patients received SRP alone. Pts were seen at 3 and 6mo.

R:Both groups showed improvement of probing depth (0.45mm vs 1.33mm) and CAL gain ( 0.46mm vs 1.13mm). both groups also had a significant reduction in BOP with no differences between the groups(17.7% vs 18.6%).

The data was further stratified into <4mm, b/t 4 and 6mm and >6mm sites. A significant difference was noted in PD for the <4mm sites in respect to baseline at both time intervals, but no differece b/t the two groups at any time interval. For 4-6mm sites, a SSD was seen between the groups at 6mo for PD ( 1.0 vs1.7mm), but NSSD for CAL. For >6mm, at 6mo the azithromycin group show SSD more reduction in PD (1.98mm vs 3.52mm), as well as CAL gain (1.32 vs 2.56). There was a trend for continued CAL gain from 3 to 6 mo in the Azithromycin group.

C: Azithromcin in cinjunction with SRP was shown to have better PD reduction and CAL gain in smokers with moderate to advanced periodontitis

Yashima 2009            ARTICLE

P: To compare the clinical and bacteriologic effects of full mouth-SRP (FM-SRP) to partial mouth-SRP (PM-SRP) in patients with chronic periodontitis.

M+M: Double masked study. 30 subjects w/ chronic periodontitis (>25 yrs old, >20 teeth, avg PD equal to or > than 4mm w/ BOP and deepest PD>6mm) participated in study. After screening, all subjects were given OHI and supragingival scaling. Two weeks later, full mouth exam and bacterial sampling performed. Subjects were divided into 3 groups, 10 pts each: FM-SRP, PM-SRP, and control. FM-SRP group started taking azithromycin 500mg 1x/day for 3 days before SRP and FM-SRP performed (avg 120 mins). PM-SRP group azithromycin 500mg 1x/day for 3 days, SRP of entire mouth completed in 3 sessions (30-40 mins each session) w/in 7 days during the effective half-life of azithromycin. Control group had conventional SRP with no antibiotics. Full-mouth clinical exam (PD, CAL gain, BOP, GI, and GCF) and bacterial sampling were performed at baseline, 1, 3, 6, 9, and 12 months after treatment. Bacterial samples collected with sterile paper points and five perio pathogens (Aa, Pi, Pg, Tf, and Td) identified in each sample with PCR-invader method.

R:

Fluoroquinolones

 

Conway 2000            ARTICLE

 

P: To compare gingival fluid Ciprofloxacin levels at healthy and inflamed human periodontal sites

M&M: 2 groups of subjects were recruited: a healthy group consisting of 7 subjects with good oral hygiene and healthy gingival tissues, and a periodontally diseased group consisting of 8 subjects with untreated adult periodontitis (characterized by probe depths ≥ 5 mm and moderate to advanced bone loss in at least two quadrants). Pregnant females and patients taking anti-inflammatory agents or antibiotics were excluded from participation in the study. Subjects from both groups were administered three doses of ciprofloxacin (500 mg BID) to establish steady state tissue levels of the agent. GF and serum samples were obtained 28 hr after the first dose of ciprofloxacin to facilitate a cross sectional comparison of ciprofloxacin levels at healthy and inflamed periodontal sites. After the 28 hr sample collection from the periodontally diseased subjects, one quadrant was randomly selected for treatment with scaling and root planing. No treatment was rendered in the other quadrant. The subjects continued taking 500 mg ciprofloxacin BID for seven additional days, returning 196 hr after the first dose of ciprofloxacin for collection of GF and serum samples.

R: The mean ciprofloxacin levels in the GF and serum of periodontally healthy subjects were 2.52 ± 0.22 μg/ml and 0.47 ± 0.05 μg/ml, respectively. In subjects with periodontitis, these levels were 2.69 ± 0.44 μg/ml and 0.61 ± 0.13 μg/ml, respectively. GF ciprofloxacin levels were significantly higher than corresponding serum levels in healthy and diseased subjects (P < 0.01), but there were no significant differences in GF or serum levels between the two subject groups. Since GF flow was significantly higher at diseased sites, however, more ciprofloxacin was distributed to these sites than to healthy sites. In the longitudinal study, GF flow at 196 hr was 16% lower at root planed sites than at untreated control sites (P = 0.412). The minor decrease in this index of inflammation was accompanied by a small (9%), but statistically significant (P = 0.007) decrease in GF ciprofloxacin levels.

CON: GF ciprofloxacin levels decreased slightly at inflamed periodontal sites after root planing, but were significantly higher than serum levels even at healthy periodontal sites. Inflammation may enhance the distribution of ciprofloxacin to diseased sites, but it is not a major determinant of GF ciprofloxacin levels.

 

Antibiotics – Augmentin

 

Winkel 1999            ARTICLE

P: To investigate the clinical and microbiological effects of initial periodontal therapy in conjunction with systemic amoxicillin and clavulanic acid (Augmentin) in pts with chronic periodontitis.

M+M: 21 healthy patients with a clinical diagnosis of generalized adult periodontitis were recruited. Clinical measurements and microbiological assessments were done at baseline, 3, and 12 months after treatment. Six weeks after initial periodontal treatment, patients were assigned randomly to 500 mg amoxicillin plus 125 mg clavulanic acid (Augmentin) or placebo, every 8 hours for 10 days. Patients returned for follow-up visits 3, 6, 9, and 12 months after completion of the medication.

R:

There were 5 smokers in each group. Mean PI at baseline was 1.1 for placebo group and 0.9 for the test group. At 3 months, the PI had dropped to 0.3 in both groups, and was maintained during the rest of the study.

The changes in BOP and GI in the course of the study were similar in both groups.

The PPD in the placebo group was 3.8 mm at baseline and 3.9 mm in the test group. A mean reduction of 1.0 mm in the placebo group and 0.9 mm in the test group was observed during the first 3 months. No further reduction in PPD was noticed during the study period in either group. There was no statistically significant difference in the PPD reduction between the 2 groups.

The change in CAL from baseline to 3 months was 0.5 mm in both groups. Between 3 and 12 months, the CAL did not change in either group. In both groups, treatment resulted in a decrease in the number of spirochetes and motile rods in positive patients, but no statistically significant difference between either group was noted in any of the dark field microscopy observations.

At baseline, 1 pt in the placebo group and 2 pts in the test group had cultures positive for AA. After therapy, AA was not detectable in the placebo group and 1 patient remained positive in the test group. In the placebo group, the number of patients positive for Pg decreased from 7 to 2 after therapy. In the test group, the 4 patients positive for Pg at baseline remained positive after therapy. In both groups, all subjects were positive for Prevotella intermedia (Pi) and Fusobacterium nucleatum (Fn) at baseline. At 12 months, all subjects had detectable subgingival Fn. 9 out of the 11 placebo and 8 of the 10 test pts remained positive for Pi. There were no differences in detection frequency of Peptostreptococcus micros (Pm) and Bacteroides forsythus (Bf) in both groups between baseline, 3, and 12 months post-treatment.

BL: The findings demonstrated that in comparison to placebo, systemic Augmentin provided no additional clinical and microbiological effects in the treatment of adult periodontitis patients when administered 6 weeks after initial therapy.

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