Aggressive Periodontitis - Guidelines for Diagnosis and Management of
|Publication: 23/02/2017 --|
|Last review: 01/01/1900|
|Next review: 01/02/2020|
|Approved By: Improving Antimicrobial Prescribing Group|
|Copyright© Leeds Teaching Hospitals NHS Trust 2017|
This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
Guidelines for Diagnosis and Management of Aggressive Periodontitis
Recommendation: Assess severity of periodontal disease for each affected tooth using probing or pocket depths according to table 2
It is, however, unusual in clinical practice to measure clinical attachment level. Pocket depths or probing depths are usually recorded, this represents the distance from the gingival margin to the depth of the probable periodontal pocket. Although this measurement is easier to record it is not considered to be valid over time the level of the gingival margin is not a fixed reference point: it may change over time as a result of inflammation or recession. In cases where there has been gingival recession, this measurement (CEJ to gingival margin in mm) can be used together with probing depth to determine CAL. (PD+Recession=CAL)
Accepting the limitations of the probing depth measurement, a classification of severity based on probing or pocket depths is generally used as follows:
Severity of bone loss should be reported as part of the radiographic findings and graded (Table 3). Other radiographic features of importance include the pattern of bone loss (horizontal or vertical); the teeth affected and furcation involvement.
Recommendation: patients with aggressive periodontitis should be given written and verbal advice on appropriate methods of toothbrushing and interdental cleaning. [Evidence level A].
Recommendation: Non-surgical periodontal therapy (NSPT) involving supra and subgingival scaling and root surface debridement using hand scalers and ultrasonic scaling instruments should be provided. [Evidence level D]
Recommendation: Patients who smoke should be advised to stop smoking. [Evidence level D] Evidence review
The first treatment modality is cause-related therapy to remove the primary aetiology, bacterial plaque. This involves oral health education,
including toothbrushing and interdental cleaning instruction to improve plaque control and reduce inflammation. The role of bacterial plaque in gingivitis and periodontitis is long established10 and as a result it is not considered appropriate to conduct clinical trials where the control group has no access to oral hygiene measures. The most recent literature therefore compares the relative effectiveness of different oral hygiene measures in reducing plaque levels, inflammation and probing depths. The majority of these studies involve patients with gingivitis and chronic periodontitis and there are no studies which look at the effect of personal oral care specifically related to the prevention or progress of aggressive periodontitis, however as bacterial plaque is the primary aetiological factor in aggressive periodontitis the findings can be related.
Much of the information which has driven public oral health messages about brushing twice a day and using interdental cleaning aids is based on longitudinal studies, which show that over a 25 year or more period, bushing more than once a day and keeping plaque scores beneath 20% reduces the risk of tooth loss.11,12 Systematic reviews of randomised controlled trials or controlled trials, show that when professional instruction is given or professional prophylaxis provided in addition to the patient’s usual oral hygiene regimen, this results in small decreases in gingival inflammation.13 Similarly, a systematic review exploring the efficacy of interdental cleaning with floss or interdental brushes over toothbrushing alone, reported minimal benefits in reducing inflammation and probing depths.14 More recently a Cochrane systematic review has identified that oscillating powered toothbrushes are more effective at removing plaque than side-to-side brushes in the short term.15 One of the recurring discussion points of these reviews is that the number of good quality studies is small, especially considering the overall size of the body of literature in this area.
Non-surgical periodontal therapy (NSPT) for periodontal disease this involves supra and subgingival scaling and root surface debridement using hand scalers and ultrasonic scaling instruments. The aim of this is to further reduce bacterial load and disrupt the subgingival biofilm. Improvement in periodontal condition is measured in the scientific literature using validated indices, which assess the amount of bleeding on probing, plaque on tooth surfaces, probing depths and CAL. The primary outcome measures are generally CAL and probing depth and it is considered that a 2mm improvement16 in these indices is clinically relevant. It should be noted therefore that in most of the studies considered in this review, power calculations were performed based on detection of 1mm change in these indices. As a result the majority of the studies are underpowered to detect a clinically significant difference.
There is one longitudinal follow up study designed to assess the outcome of NSPT alone in patients with aggressive periodontitis.16 This involved a relatively large number of patients (n=79) and treatment detailed as 4 appointments at which oral hygiene instruction and supra and subgingival debridement and root surface instrumentation were provided, there was no control group. Periodontal indices were reviewed 10 weeks post operatively and improvements in bleeding and plaque scores and mean decreases in probing depths and gains in clinical attachment were described but improvements in mean probing depths were modest (2.11+/-2.01 mm).
The majority of evidence for the efficacy of NSPT in aggressive periodontitis comes from randomised controlled trials (RCTs) where it acts as the control for NSPT provided with adjunctive antibiotics. These studies mostly show that with NSPT alone periodontal parameters will improve in the 6 months following treatment.17-24 However, studies with a follow up of 6 months or more seem to show that pocket depths and clinical attachment levels are less well sustained than where antimicrobials are provided.17,25 Due to the limited number of studies and the quality of the published information is it not possible to draw conclusions in this regard.
|Empirical Antimicrobial Treatment|
Empirical antimicrobial therapy is a term used to describe therapy started prior to availability of microbiology results or if a microbiological diagnosis is not going to be possible. Most antimicrobial prescribing for aggressive periodontitis is therefore empirical as microbiological sampling is not part of routine practice.
Recommendation: systemic antibiotics should be reserved for patients who do not show improvement at review carried out 2-3 months following completion of debridement, where other factors (e.g plaque control) are favourable. They should always be prescribed as an adjunct to NSPT. [Evidence level D]
Recommendation: first line antimicrobial regimen would be oral Amoxicillin 500mg 8-hourly plus oral Metronidazole 500mg 8-hourly for seven days OR Azithromycin 500mg OD for 3 days in penicillin allergic patients.
Evidence for the efficacy of antimicrobial therapy.
Unlike chronic periodontitis, aggressive periodontitis has been associated with the specific bacteria, namely Aggregatibacter actinomycetemcomitans and Porphymonas gingivalis. Both of these bacterial species produce a number of virulence factors and have the ability to invade host tissues, which protects from mechanical NSPT. As a result of this the use of systemic antimicrobials may have role to play, however, convincing evidence of effectiveness from appropriately powered studies is lacking. While some consider that antibiotics should be used as an adjunct to NSPT which reduces overall bacterial load and disrupt the biofilm theoretically making bacteria more susceptible to antibiotics,26 other studies indicate that antibiotics do not reduce the total counts of streptococci.27 Although recent work is lacking, A. actinomycetemcomitans is usually sensitive to Amoxicillin , but frequently resistant to macrolides.28
Table 4 displays keys features of the randomised placebo controlled trials on this subject. These mainly involve patients with generalised aggressive periodontitis, however four trials involving localised aggressive periodontitis were completed in the 1990s. As stated previously the majority of these RCTs are underpowered to detect a difference that would be considered clinically significant. They also use a variety of different antibiotic regimens and have reported the data in different ways. As a result there is no recognised consensus regarding the choice of antibiotic, dosage or timing.
A systematic review in 2012 combined the data from trials that used a combination of Amoxicillin and Metronidazole as an adjunct to NSPT in a meta-analysis.29 The results suggest that these antibiotics do provide an additional clinical benefit in terms of reducing probing depth and CAL. However, even though there was no heterogeneity detected between the studies, this should be considered with some caution due to the small size of the studies. With such limited follow up it is impossible to know whether the differences achieved with antibiotics are sustained in the longer term.19
It has been suggested that poor compliance with antibiotic regimens adversely affects the outcome of periodontal treatment.24 Azithromycin may therefore offer advantages over the more frequently investigated combination of Amoxicillin and Metronidazole which is generally prescribed over 7-10 days TDS. When Azithromycin is prescribed as a 3 day ODS course, serum and gingival concentrations of Azithromycin remain above the minimal inhibitory concentration for 7 days following administration.30 Unfortunately the amount of evidence for Azithromycin in treatment of AgP is limited to just one RCT.17
The harms of antimicrobials, aside from antimicrobial resistance, should also be considered, for example in one trial 30% of patients in the antibiotic test group suffered nausea, diarrhoea or vomiting24 – a significant concern given the modest dental benefits.
Timing of antibiotics in relation to clinical treatment
Recommendations: In cases of AgP, antibiotics should be prescribed with the second course of NSPT. Antibiotic prescription should be given when debridement is completed, with this occurring within as short a timescale as possible. [Evidence level D]
A review by Herrera et al 200832 concluded that there was a lack of direct evidence regarding when the course of antibiotics should start in relation to debridement. However, within the scope of their review concluded indirectly, that antibiotics should start on the day of debridement completion. Additionally they emphasised that debridement should be of adequate quality should be completed within as short a timescale as possible, ideally less than 1 week.
The conclusion above was based in part on the results of two cohort trials run separately but with identical methodologies apart from timing of the antibiotic intervention.33 When the probing depths and CAL changes in each group were compared at 6 month follow up, changes were more significant in the group who received antibiotics at the beginning of treatment. It was suggested that one of the reasons for this is that gingival inflammation enhances the delivery of antibiotic to the periodontal pocket because of the associated increases in the flow of gingival crevicular fluid.
In 2011, Griffiths completed the second phase of trial,24,31 which saw the original placebo group given the same regimen of oral antimicrobials
(Amoxicillin 500mg tds plus Metronidazole 500mg tds 7/7) as the test group during their retreatment at 6 months. Both groups showed improvements in PD and CAL gain. The initial treatment group had a statistically significant better improvement in deep pockets (pockets initially >7mm, 0.9mm change P=0.003) than the delayed treatment group, but the differences in changes in other parameters were insignificant.
Beliveau et al reported on an ongoing trial involving two cohorts of patients with localised AgP who received NSPT, with antibiotics (Amoxicillin 500mg and Metronidazole 250mg) being prescribed immediately or 3 months following debridement.34 Results of this retrospective study suggest that by prescribing antibiotics immediately, periodontal parameters improve more quickly, however by 6 months both regimens were effective.
|Directed Antimicrobial Treatment (when microbiology results are known)|
Microbiology sampling is not clinically available for AgP and therefore this is not relevant.
|Duration of Treatment|
Table 4 indicates that most studies have used 7-14 days treatment but the choice of duration has been arbitrary. That dosing regimen should be as short as possible, whilst still providing effective therapy. The search of the literature, detailed above (Table 4) reveals no consensus with regards to the duration of antibiotic therapy. There are no studies comparing different durations of the same antibiotic prescription. There is also no consensus as to how long the level of antibiotic needs to remain above the minimum inhibitory concentration following NSPT to be effective.
If Azithromycin is prescribed, it has been suggested that a 3 day course of 500mg ODS is effective to produce levels of the drug above the minimum inhibitory concentration for 7-10 days.17,30 For Amoxicillin and Metronidazole , the available RCTs (Table 4) describe several regimens and the choice of these is not evidence based.18-24,31 They also do not provide information about drug concentrations within the periodontal tissues. A recent controlled trial investigated the concentration of antibiotics in the periodontal tissues of patients undergoing periodontal surgery and crown lengthening who were prescribed 500mg amoxicillin and 250mg Metronidazole for 7 days. The concentrations of both drugs in the gingival tissues were measured at the end of this course of treatment and were reported to be well above the minimum inhibitory concentration required.35 There was no follow up beyond 7 days so it is unclear how long these levels are maintained. This one study does suggest, however, that regimens extending beyond 7 days are not indicated.
There are increasing concerns about antimicrobial resistance (AMR) and a drive against prescribing antimicrobials where there is a lack of clear evidence of benefit. AMR is a harm that needs to be considered at the time of prescribing and guideline preparation. A seven day course of co- amoxiclav doubled the counts of oral streptococci that were resistant to penicillin, an effect which persisted for many months.27 A single dose of Amoxicillin 3g reduces the numbers of penicillin-streptococci in saliva but can also select for penicillin-resistant streptococci.36 RCT evidence indicates that seven days of clarithromycin or three days of Azithromycin cause a 50% increase in macrolide resistance.37
Since acute aggressive periodontitis is caused by an imbalance in the normal gingival microbial flora, we advise that courses of antimicrobial therapy should be limited to 7 days for Amoxicillin and Metronidazole and 3 days for Azithromycin .
|Switch to oral agent(s)|
Therapy for AgP is generally given orally in the first instance so this is not relevant.
Clinical algorithms: a summary of treatment protocols is provided in the attached flowchart document “Aggressive Periodontitis Treatment Guideline”
Treatment of aggressive periodontitis aims to achieve periodontal stability by reducing overall inflammation, pocket depth and improving clinical attachment levels. Due to the nature of periodontal disease it is not unusual to see that, although overall periodontal health improves following treatment, disease activity continues to persist at isolated sites.
Clinical indicators of successful treatment could be considered to be based on factors identified as positive predictors for site progression:38-40
1. Probing depths ≤5mm
An important feature of successful treatment is control of risk factors where possible and these should be followed up, objectively where possible.
Repeated courses of antibiotics are not indicated to manage aggressive periodontitis where no efforts have been made to control risk factors. Further treatment, involving surgery or local antimicrobials used alongside further subgingival debridement may be indicated if deep pockets (>5mm) and bleeding on probing persist after NSPT as evidence from longitudinal studies suggests that these are more at risk of experiencing further periodontal breakdown in both chronic periodontitis40 and aggressive periodontitis39.
Evidence relating specifically to surgery in aggressive periodontitis cases is limited to case reports and case series.41 Results of a meta-analysis in 2005 looking at outcomes in chronic periodontitis, suggest that surgery is indicated where pockets of greater than 6mm in depth persist, as these sites respond to surgical treatment better than to further NSPT.42 Depending on local factors, this could be open flap debridement or regeneration using biomaterials.
No antibiotics are indicated as prophylaxis for this type of surgery.43
There have only been two studies comparing the use of local antimicrobials, prescribed as an adjunct to NSPT, with NSPT alone. Both of these describe the first course of treatment rather than treatment targeting sites which have not responded to the initial stage.
Local antibiotics have advantages in that, as they are deposited directly into the affected periodontal pocket, the risks of adverse effects and antimicrobial resistance are reduced. This method of delivery is particularly appropriate where there are a limited number of sites to be treated, this may be in localized disease or to target residual sites.
Unsal et al performed a randomized controlled trial involving patients with localized aggressive periodontitis.44 The 2 test groups received subgingival delivery of 1% chlorhexidine gel and 40% tetracycline gel, however, these interventions did not provide any benefit over NSPT alone 3 months after final debridement. The second trial investigated the effect of subgingival tetracycline fibres in comparison to NSPT using a split mouth design in patients with generalized aggressive periodontitis.45 Six months after treatment they reported a statistically significant improvement in probing depths and CAL but these differences amounted to less than 1mm. Given the restricted quality of the literature, it has been suggested that the decision to use local antimicrobials be made on an individual basis rather than it being evidence based.41
The conclusion of this review is that there is insufficient evidence to support the use of locally delivered antimicrobials in the treatment of aggressive periodontitis in the initial stage of therapy. They may be considered for localised areas of increased probing depths which persist following standard management detailed in this guideline.
There are no studies regarding the optimal recall intervals for follow up of patients with AgP however it is generally considered that maintenance therapy is key to controlling disease progression and reducing tooth loss.46-48
|Target patient group:|
|Target professional group(s):||Secondary Care Doctors
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)
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- Hughes FJ, Syed M, Koshy B, et al. Prognostic factors in the treatment of generalized aggressive periodontitis: II. Effects of smoking on initial outcome. J Clin Periodontol 2006; 33(9): 671-6.
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- European guidelines on radiation protection in dental radiology
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- van der Weijden GA, Hioe KP. A systematic review of the effectiveness of self-performed mechanical plaque removal in adults with gingivitis using a manual toothbrush. Journal of clinical periodontology 2005; 32 Suppl 6: 214-28.
- Slot DE, Dorfer CE, Van der Weijden GA. The efficacy of interdental brushes on plaque and parameters of periodontal inflammation: a systematic review. International journal of dental hygiene 2008; 6(4): 253-64.
- Deacon SA, Glenny AM, Deery C, et al. Different powered toothbrushes for plaque control and gingival health. The Cochrane database of systematic reviews 2010; (12): CD004971.
- Hughes FJ, Syed M, Koshy B, et al. Prognostic factors in the treatment of generalized aggressive periodontitis: I. Clinical features and initial outcome. J Clin Periodontol 2006; 33(9): 663-70.
- Haas AN, de Castro GD, Moreno T, et al. Azithromycin as an adjunctive treatment of aggressive periodontitis: 12-months randomized clinical trial. J Clin Periodontol 2008; 35(8): 696-704.
- Casarin RC, Peloso Ribeiro ED, Sallum EA, Nociti FH, Jr., 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(8): 988-98.
- 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(8): 1121-30.
- Baltacioglu E, Aslan M, Sarac O, Saybak A, Yuva P. Analysis of clinical results of systemic antimicrobials combined with nonsurgical periodontal treatment for generalized aggressive periodontitis: a pilot study. Journal 2011; 77: b97.
- 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. Journal of clinical periodontology 2010; 37(4): 353-65.
- Yek EC, Cintan S, Topcuoglu N, Kulekci G, Issever H, Kantarci A. Efficacy of amoxicillin and metronidazole combination for the management of generalized aggressive periodontitis. J Periodontol 2010; 81(7): 964-74.
- 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(4): 254-64.
- Guerrero A, Griffiths GS, Nibali L, et al. Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol 2005; 32(10): 1096-107.
- 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. Journal of periodontology 2001; 72(3): 275-83.
- Mombelli A. Heresy? Treatment of chronic periodontitis with systemic antibiotics only. J Clin Periodontol 2006; 33(9): 661-2.
- Cremieux AC, Muller-Serieys C, Panhard X, et al. Emergence of resistance in normal human aerobic commensal flora during telithromycin and amoxicillin-clavulanic acid treatments. Antimicrobial agents and chemotherapy 2003; 47(6): 2030-5.
- Madinier IM, Fosse TB, Hitzig C, Charbit Y, Hannoun LR. Resistance profile survey of 50 periodontal strains of Actinobacillus actinomyectomcomitans. J Periodontol 1999; 70(8): 888-92.
- Sgolastra F, Petrucci A, Gatto R, Monaco A. Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis. Journal of periodontology 2012; 83(6): 731-43.
- Blandizzi C, Malizia T, Lupetti A, et al. Periodontal tissue disposition of azithromycin in patients affected by chronic inflammatory periodontal diseases. J Periodontol 1999; 70(9): 960-6.
- Griffiths GS, Ayob R, Guerrero A, et al. Amoxicillin and metronidazole as an adjunctive treatment in generalized aggressive periodontitis at initial therapy or re-treatment: a randomized controlled clinical trial. J Clin Periodontol 2011; 38(1): 43-9.
- Herrera D, Alonso B, Leon R, Roldan S, Sanz M. Antimicrobial therapy in periodontitis: the use of systemic antimicrobials against the subgingival biofilm. Journal of clinical periodontology 2008; 35(8 Suppl): 45-66.
- Kaner D, Christan C, Dietrich T, Bernimoulin JP, Kleber BM, Friedmann A. Timing affects the clinical outcome of adjunctive systemic antibiotic therapy for generalized aggressive periodontitis. J Periodontol 2007; 78(7): 1201-8.
- Beliveau D, Magnusson I, Bidwell JA, et al. Benefits of early systemic antibiotics in localized aggressive periodontitis: a retrospective study. Journal of clinical periodontology 2012; 39(11): 1075-81.
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- Heitz-Mayfield LJ. How effective is surgical therapy compared with nonsurgical debridement? Periodontology 2000 2005; 37: 72-87.
- Guidelines for the Antibiotic Prophylaxis for Periodontal Surgery: Leeds Health Pathways 2013
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- Sakellari D, Vouros I, Konstantinidis A. The use of tetracycline fibres in the treatment of generalised aggressive periodontitis: clinical and microbiological findings. Journal of the International Academy of Periodontology 2003; 5(2): 52-60.
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