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Periodontal diseases are a group of chronic inflammatory disorders caused by pathogenic bacterial species located in the sub-gingival niche, it is characterized by breakdown of connective tissue and alveolar bone in a susceptible patient.. Periodontitis is generally treated by non- surgical mechanical debridement (also referred to as scaling and root planning SRP), in which plaque, calculus and necrotic cementum are removed from root surface to create a local environment that is biologically favorable for wound healing followed by regular periodontal maintenance and the oral hygiene instructions.
The bacterial etiology of periodontal diseases has provided the basis for use of systemic antibiotic therapy in their over all management. But their use in management of periodontitis has been debated over decades because of the multiple bacterial etiologies of periodontal diseases and lack of unbiased evidence-based assessment of possible benefits of systemic antibiotics.
However, two systematic reviews presented at the European and World periodontal workshops have reported the adjunctive use of antibiotics in the treatment of periodontitis, thus providing unbiased evidence based assessment of the possible benefits of systemic antibiotics in treating periodontal diseases.
While treating periodontal disease, we sometimes face a situation, where the patient continues to demonstrate loss of periodontal attachment despite careful high quality of mechanical debridement. Therefore antibiotics are prescribed in such cases who do not respond to conventional root surface instrumentation (RSI). The purpose of adjunctive use of systemic antibiotics is to enable the resolution of inflammation in the periodontal pocket by further reducing the bacterial load which stay in the biofilms.
The 5th European Workshop of Periodontology stated that dental plaque have properties similar to that of biofilms and microbial communities, resulting in clinical outcome of reduced susceptibility to antibiotics. Having said this, the effect of antibiotics on the sub gingival biofilm is highly relevant when making decisions on use of antibiotics to treat periodontal diseases.
The bacteria in biofilm are 500 times more resistant to antibiotics than the same bacteria grown as pure cultures. These biofilms are relatively impervious to antibiotics and provide protection to the bacteria contained in them. Therefore minimum inhibitory concentration (MIC) of the antibiotics is never achieved. This makes the mechanical disruption of biofilm critical, when the antibiotics are used.
The emergence of resistance bacterial strains should be considered when deciding to use antibiotics. These resistant strains have reduce susceptibility to the antibacterial agent, either by selection i.e. the overgrowth of bacteria that are resistant to antibiotics following removal of susceptible bacteria or by horizontal gene transfer, in which there is transfer of gene that codes for resistance to antibiotics between bacterial species and all major pathogens. This has a direct impact on the therapeutic advantages of antibiotics that we may use clinically. This in turn might sometimes lead to the failure of therapy.
To avoid this, antibiotics should be used in a responsible way. Not every patient with periodontal disease should be given antibiotics. Factors such as systemic wellbeing of patient, concomitant medical conditions, and nature of infecting agents should be taken into consideration.
In the treatment of periodontal diseases with antibiotics one of the key issues is the importance of biofilm disruption. Keeping this in mind following questions specifically need to be addressed:
1) Can systemic antibiotics be used efficiently without disrupting the biofilm?
A systematic review published in 2003 stated that use of antibiotic alone was minimal and short term because of relatively impervious biofilm. One study reported development of multiple periodontal abscesses in patients with advanced periodontal diseases, who were put on monotherapy without RSI, this was because of change in the composition of sub gingival microbiota without the subgingival debridement Thus RSI ensuring adequate disruption of biofilm remains the appropriate treatment option when prescribing antibiotics.
2) Is the efficacy of adjunctive therapy dependant on sequence of debridement?
The Sixth European workshop on Periodontology discussed various questions related to use of antibiotics as an adjunctive therapy. They concluded "at present there is no direct evidence of a specific protocol for the use of adjunctive systemic antibiotics with non-surgical mechanical debridement. But, indirect evidence suggests that antibiotic intake should start on the day of debridement completion; it should be completed within short time (preferably < 1 week) and with an adequate quality. Furthermore they stated that the drug therapeutic levels should be achieved at the time of debridement completion and all the debridement should be carried out preferably within 7days."
It is also seen that, higher operator skills and providing the drug therapy immediately after the debridement significantly improve the clinical results. At present data is inadequate to support if the type of debridement (surgical or non surgical) can have an impact on the clinical outcomes of the adjunctive antibiotic therapy.
In the treatment of periodontal disease it is often difficult to decide when to start the antibiotic therapy, and who should receive them? Most of the times an appropriate antibiotic is selected followed by diagnosis and the clinician's decision. However the antibiotic usage should be restricted to patients with aggressive, severe/progressing forms of periodontitis, and periodontal diseases associated with systemic manifestations (fever, malaise). While making the decision, plaque control and patient compliance issue should also be borne in mind.
Antibiotics are naturally occurring or synthetic organic substances which in low concentration either inhibit (bacteriostatic) the growth or kill selective microorganisms (bactericidal). They can either be used as single-drug regimens (use of penicillin, tetracycline, metronidazole alone) or as combined antibiotics (metronidazole/amoxicillin, metronidazole/Augmentin). Sometimes even serial drug regimens are used (dose of doxycycline initially followed by metronidazole or Augmentin). They can be administered systemically or locally.
Systemic antibiotics are used more than local antibiotics. One main reason is that they are simple to use and easily reach multiple sites of disease. They even reduce the pathogens from oral mucosa and other extra-dental sites like tongue, tonsilar areas. Thus they reduce the risk of translocation of organisms to periodontal pocket and their future recolonization.
Most often a combination drug therapy is used to treat periodontal diseases, because it offers three major advantages: It can target multiple species with different antibiotic susceptibility, overcomes the drug protective effect of biofilm, it can target the resistant strains. One way by which the combination therapy targets the resistant strains is by its synergistic but different mechanism of action. E.g. Amoxicillin/metronidazole, metronidazole/ciprofloxacin.
. Another way is by the antagonist effect E.g. bacteriostatic effect of tertracyclines and bactericidal effect of Î²-lactum antibiotics.
The Use of antibiotics in specific periodontal diseases:
Systemic antibiotic therapy is not indicated for treatment of chronic periodontitis because of the variations in the microbial flora and variation in the disease progression among patients. It is well documented that the majority of chronic periodontitis cases can be treated successfully by mechanical debridement, with adequate oral hygiene instructions and periodical review.
Aggressive Periodontitis (AP):
Previously known as 'juvenile periodontitis' and 'rapidly progressive periodontitis' AP can be classified as localized or generalized. Because of the rapid progression of disease these cases should be referred for an assessment to a periodontal specialist, while the general dentist may provide initial or supportive therapy. A recent systematic review concluded that adjunctive systemic antibiotic therapy should be considered in AP cases..
The localized AP is associated with high levels of sub gingival Aggregatibacter actinomycetemcomitans (Aa). Aa possesses many virulence factors, including the ability to invade the soft tissues. Thus the organism can be protected during RSI. The reservoirs of Aa in the tissues permit their rapid recolonization. An adjunctive therapy should therefore be considered. In past a two week 1g tetracycline/day, as an adjunct to full mouth RSI was used for treating AP. But, the disease relapsed in as many as 25% patients, which was most likely because of the emergence of tetracycline resistant strains of Aa during the 1980s and 1990s.
According to current literature, combined antibiotic regimen of metronidazole (400 mg 3 times daily) and amoxicillin (250 mg 3 times daily) for 7 days appears to be the treatment of choice for AP. This should be adjunct to full mouth RSI which can be done in quadrants under local anesthesia, followed by oral hygiene instructions (OHI). RSI should be completed preferably within 7 days so that efficient drug levels are achieved when it is completed. One study shows adjunctive use of Azithromycin has a potential to improve treatment outcome in young patients with AP. In E. corrodens infections, which are resistant to amoxicillin, metronidazole/ Augmentin combination can be used. Adjunctive therapy of metronidazole/amoxicillin should be considered in Generalized AP if multiple suppurating periodontal abscesses are present.
Systemic antibiotics can be used to treat periodontal abscess if the infection is spreading and/or systemic involvement is there. The suggested regimen is amoxicillin 250 mg 3
times daily for 5 days or a short course of metronidazole 200 mg 3 times daily for 5 days or a single high dose of amoxicillin (3 g). In cases of acute periodontal abscess a 2-3 days short course of antibiotics is sufficient, if abscess drainage is established.
Necrotizing Ulcerative Gingivitis (NUG) and Periodontitis (NUP)
NUG previously known as "Acute Necrotizing Ulcerative Gingivitis (ANUG)" is an acute gingivitis spirochaetal infection which is extremely painful. It is often associated with smoking, stress, and possibly HIV infection. Most of the cases of NUG are treated by a specialist. Treatment involves supra-gingival scaling, use of chlorhexidine mouth wash to reduce the plaque mass and 200 mg of metronidazole 3 times a day for 3 days is given after which full mouth RSI should be done and OHI are given, the patient is advised to stop smoking. The treatment of NUP is also similar to treatment of NUG.
Having listed the above conditions and the antibiotics used to treat them; we often cannot get same therapeutic results with specific antibiotic or their combination in all cases of a specific condition. This is because the sub-gingival microbial profile is not same in all patients. The efficacy of an antibiotic depends upon the absorption rate and their MIC achieved in the gingival crevicular fluid (GCF). But the optimal dosage of agents is still not clear and most current regimens used are empirically developed.
While giving the systemic antibiotics their safety issues should be considered which include gastrointestinal problems such as diarrhoea. In rare instances, severe adverse effects like anaphylactic reaction and pseudomembranous colitis have been observed. Patient's medical history should be always taken prior to start of systemic antibiotics. Their use in pregnant women is also a concern.
Locally applied controlled delivery products are also used for the treatment of periodontal diseases. They achieve higher concentrations in GCF than the systemic antibiotics while having almost negligible impact on the other parts of body. Tetracycline and doxycycline are commercially available as (Actisite and Atridox respectively). 25% metronidazole dental gel is available as Elyzol.
A survey on systemic and local antibiotic use shows that use local antibiotic therapy is not common as compared to systemic antibiotic. This is because lack of awareness among the dentist and their delivery is time consuming, most often blind ended since the operator is not aware of the exact location where they need to be delivered. But this does not mean that they have no place in periodontal therapy. They are ideal for treatment of individual sites who fail to respond to conventional therapy and in treating the immunocompromised patients with systemic diseases like diabetes.
If the systemic antibiotics are to be used then they must be used as an adjunctive treatment and not as monotherapy. The subgingival biofilm must be disrupted by adequate mechanical debridement as without this, the antibiotics are less effective. Antibiotic resistance should be kept in mind and a combination drug regimen should be used. They should be used only in specific patient groups like aggressive priodontitis, NUG, NUP. Patient's medical history must be considered and they should be informed of possible adverse effects. The results are greatly improved by high operator skills. Finally the decision to prescribe them should be done on individual basis.
Ideally to choose an antibiotic the culture of infective organism and sensitivity testing should be done. This is difficult to perform in dental practice because reliable diagnostic systems are not readily available. Thus, neither the identity of the causative agent nor the microbial susceptibility to the antimicrobial agent is readily available to the dental practitioner. Therefore (thus therefore 2 conclusive statements??)the treatment with or without antibiotics is largely based upon somewhat ambiguous clinical parameters.