DENTAL SCIENCE - REVIEW ARTICLES
Year : 2012 | Volume
: 4 | Issue : 6 | Page : 252--255
Antibiotics in the management of aggressive periodontitis
Abinaya Prakasam1, S Sugumari Elavarasu1, Ravi Kumar Natarajan2,
1 Department of Periodontics, JKK Nataraja Dental College and Hospital, Komarapalayam, India
2 Department of Periodontics, Tagore Dental College and Hospital, Vandalur, Chennai, Tamilnadu, India
Department of Periodontics, JKK Nataraja Dental College and Hospital, Komarapalayam
Aggressive periodontitis, although not rare, is a fairly unknown condition. Little is known about its optimal management. While majority of patients with common forms of periodontal disease respond predictably well to conventional therapy (oral hygiene instructions (OHI), non-surgical debridement, surgery, and Supportive Periodontal therapy (SPT)), patients diagnosed with aggressive form of periodontal disease often do not respond predictably/favorably to conventional therapy owing to its complex multi-factorial etiology. Protocols for treating aggressive periodontitis are largely empirical. There is compelling evidence that adjunctive antibiotic treatment frequently results in more favorable clinical response than conventional therapy alone. This article mainly focuses on the role of adjunct use of pharmacological agents in improving the prognosis and treatment outcome of aggressive periodontitis patients.
|How to cite this article:|
Prakasam A, Elavarasu S S, Natarajan RK. Antibiotics in the management of aggressive periodontitis.J Pharm Bioall Sci 2012;4:252-255
|How to cite this URL:|
Prakasam A, Elavarasu S S, Natarajan RK. Antibiotics in the management of aggressive periodontitis. J Pharm Bioall Sci [serial online] 2012 [cited 2021 Sep 17 ];4:252-255
Available from: https://www.jpbsonline.org/text.asp?2012/4/6/252/100226
Aggressive periodontitis, by definition, causes rapid destruction of the periodontal attachment apparatus and the supporting alveolar bone. It can present in a localized or generalized form. Two common features of both forms are (1) rapid attachment loss and bone destruction in an otherwise clinically healthy patient and (2) a familial aggregation.  These patients often present with limited microbial deposits that seem inconsistent with the severity of tissue destruction. However, the deposits that are present often have elevated levels of Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans,  or Porphyromonas gingivalis. These patients may also present with phagocyte abnormalities and a hyperresponsive monocyte/macrophage phenotype. These clinical, microbiological, and immunologic features would suggest that patients diagnosed with aggressive periodontitis would have poor prognosis. The responsiveness of aggressive periodontitis to conventional periodontal treatment is unpredictable, and the overall prognosis for these patients is poorer than for patients with chronic periodontitis.
However, the clinician should consider additional specific features of the localized form of disease when determining the prognosis. Localized aggressive periodontitis usually occurs around the age of puberty and is localized to first molars and incisors.  The patient often exhibits a strong serum antibody response to infecting agents, which may contribute to localization of the lesions. When diagnosed early, these can be treated conservatively with OHI and systemic antibiotic therapy, resulting in an excellent prognosis. When more advanced disease occurs, the prognosis can still be good if the lesions are treated with debridement, local and systemic antibiotics, and regenerative therapy. In contrast, patients with generalized form of the disease are also young with generalized interproximal attachment loss and a poor antibody response. Secondary contributing factors such as cigarette smoking are often present. These factors, coupled with alteration in host defense seen in many of these patients, may result in a case that does not respond well to conventional periodontal therapy (scaling with root planing, oral hygiene instruction, and surgical intervention). Therefore, these patients often have a fair, poor, or questionable prognosis, and the use of systemic antibiotics should be considered to help control the disease.
The presence of periodontal pathogens, specifically A. actinomycetemcomitans, has been implicated as the reason that aggressive periodontitis does not respond to conventional therapy alone. These pathogens are known to remain in the tissues  after therapy and re-infect the pocket. The identification of A. actinomycetemcomitans as a major culprit and the discovery that this organism penetrates the tissues offered another perspective to the pathogenesis of aggressive periodontitis and offered new hope for therapeutic success, namely antibiotics. The use of systemic antibiotics was thought to be necessary to eliminate pathogenic bacteria from the tissues. 
There is compelling evidence that adjunctive antibiotic treatment frequently results in a more favorable clinical response than mechanical therapy alone. Indeed, several authors have reported success in the treatment of aggressive periodontitis using antibiotics as adjuncts to standard therapy.
Empirical Therapy Versus Microbial Testing
The choice of antibiotics can either be empiric or guided by information about the nature of the involved pathogenic microorganism(s) and/or their antibiotic susceptibility profile. Currently, there exists no direct evidence that microbiologic diagnosis and targeted selection of antibiotic regimen provides an additional benefit compared to empiric use.  In practice, antibiotics are often used empirically without microbial testing. Studies conducted to evaluate the effectiveness of microbial testing concluded that the usefulness of microbial testing may be limited and that empirical use of antibiotics, such as a combination of amoxicillin and metronidazole, may be more clinically sound and cost effective than bacterial identification and antibiotic-sensitivity testing. The use of such measures can still be considered whenever a case of aggressive periodontitis is not responding or if the destruction continues despite good therapeutic efforts.
Rationale for Antibiotic Therapy
The rationale for pharmacological agents in management of aggressive forms of periodontal disease is eliminating the initiating factors and diseased tissues by conventional therapy and augmenting it with systemic pharmacological agents to eliminate the pathogens left in the tissues. It is to be emphasized, in such cases, that use of antibiotics is as important as the conventional therapy.  Mechanical treatment may not predictably eliminate putative pathogens such as A. actinomycetemcomitans from sub-gingival area due to them being inaccessible to mechanical intervention, especially in areas such as root concavities, furcation, and their ability to invade periodontal tissues and dentinal tubules. Persistence in non-dental areas such as dorsum of tongue or tonsils is again an important area of concern.
While the use of antibiotics in periodontal treatment will probably always be controversial, reports from both the American Academy of Periodontology and the European Federation of Periodontology contain valuable guidance for their use. Both these reports, following exhaustive literature searches, determined that patients with aggressive periodontitis appear to benefit from the adjunctive use of systemic antibiotics during treatment.
Systemic Administration of Antibiotics
An ideal antibiotic for use in prevention and treatment of periodontal disease should be specific for periodontal pathogens, allogenic and nontoxic, substantive, not in general use for treatment of other diseases, and inexpensive.  Currently, an ideal such antibiotic does not exist.  Although oral bacteria are susceptible to many antibiotics, no single antibiotic at concentrations achieved in body fluids inhibits all putative periodontal pathogens. Indeed, it is suggested that a combination of drugs may be necessary to eliminate all putative pathogens from some periodontal pockets.
Tetracyclines have been widely used in treating refractory forms of periodontal disease, including localized aggressive periodontitis. They have the ability to concentrate in the periodontal tissues and inhibit the growth of A. actinomycetemcomitans.  In addition, they exhibit anti-collagenase effect which can inhibit tissue destruction and aid in bone regeneration. Mechanical removal of calculus and plaque from the root surfaces may not eliminate the bacteria from periodontal tissues. Systemic tetracycline can eliminate tissue bacteria and has been shown to arrest bone loss and suppress microbial levels in conjunction with scaling and root planing.  The dosage recommended is 250 mg, 4 times daily (qid).
The importance of doxycycline arises from the fact that it has higher availability in gingival crevice when compared to other drugs, 7-20 times more than any other drug.  The second most important factor is its dual mechanism of action. As an antibiotic agent, it has more significant action against A. actinomycetemcomitans, warranting its use in aggressive periodontitis. 
Also, its actions do not limit to antimicrobial activity, but include the following host modulating properties:
AnticollagenaseAnti-inflammatoryInhibition of bone resorptionPromotes reattachmentConcept of low dose doxycycline (LDD)Chemically modified tetracycline (CMT).
Because doxycycline can be given only once daily, it makes it more patient compliant. Compliance is also favored because absorption from the GI tract is only slightly altered. The recommended dosage as an anti-infective agent is 100mg bid on the first day, followed with 100mg once daily for 21 days.
Metronidazole is not the drug of choice for treating A. actinomycetemcomitans infections. However, it is effective against them when used in combination with other antibiotics.  It is also effective against anaerobes such as P. gingivalis and Prevotella intermedia.  Studies have suggested that when combined with amoxicillin or amoxicillin-clavulanate potassium, metronidazole may be of value in the management of patients with aggressive periodontitis.
Amoxicillin is found to be useful in the management of patients with aggressive periodontitis, in both localized and generalized forms.  Recommended dosage is 500 mg tid for 8 days. 
The combination of amoxicillin and clavulanate potassium makes the antibiotic resistant to penicillinase enzymes produced by some bacteria. It has been found to be useful in the management of localized form of aggressive periodontitis,  and also to arrest alveolar bone loss.
Ciprofloxacin is active against gram-negative rods, including all facultative and some anaerobic putative periodontal pathogens. Since it demonstrates minimal effect on Streptococcus species, which are associated with periodontal health, its administration may facilitate the establishment of microflora associated with periodontal health. At present, ciprofloxacin is the only antibiotic in periodontal therapy to which all strains of A. actinomycetemcomitans are susceptible. It has also been used in combination with metronidazole. 
Azithromycin is found to be effective against anaerobes and gram-negative bacilli. The concentration of azithromycin in tissue specimens from periodontal lesions is significantly higher than that of normal gingiva.  It also has been proposed that this drug penetrates fibroblasts and phagocytes, suggesting that it is actively transported to sites of inflammation by phagocytes and then released directly into the sites of inflammation as the phagocytes rupture during phagocytosis. 
Recent data suggest that azithromycin can be an effective adjunctive therapy for increasing attachment levels in patients with aggressive periodontitis. Therapeutic dosage is single dose of 250 mg/day for 5 days, after an initial loading dose of 500 mg.
Serial and Combination Therapy
Periodontal infections contain a wide diversity of bacteria; hence, no single antibiotic can be effective against all putative pathogens.  This "mixed" infection" can include a variety of aerobic, microaerophilic, and anaerobic bacteria, both gram negative and gram positive. This scenario makes it mandatory to use more than one antibiotic, either serially or in combination. 
The metronidazole-amoxicillin and metronidazole-amoxicillin-clavulanate potassium combination caused excellent elimination of many organisms in localized aggressive periodontitis that had been treated unsuccessfully with tetracycline and mechanical debridement.  Metronidazole-ciprofloxacin combination is effective against A. actinomycetemcomitans; metronidazole targets obligate anaerobes, and ciprofloxacin targets facultative anaerobes. This is very powerful combination against mixed infections. This combination provides a therapeutic benefit by reducing or eliminating pathogenic microorganisms and offers a prophylactic benefit by giving rise to predominantly streptococcal microflora. 
Antibiotics that are bacteriostatic (e.g. tetracycline) generally require rapidly dividing microorganisms to be effective. They do not function well if a bactericidal antibiotic (e.g. amoxicillin) is given concurrently. When both these drugs are required, they are best given serially, not in combination.
The use of local delivery method to administer antibiotic offers a novel approach to the management of periodontal "localized" infections. The primary advantage is that smaller doses of topical agents can be delivered inside the pocket, avoiding the side effects of systemic antibacterial agents, while increasing the exposure of target microorganisms to higher concentrations and therefore more therapeutic levels of the medication. 
Full mouth disinfection
Another approach to antimicrobial therapy in the control of infection associated with periodontitis is the concept of full mouth disinfection. The procedure consists of full mouth debridement completed in two appointments within a 24-h period. In addition to scaling and root planing, the tongue is brushed with chlorhexidine gel (1%) for 1 min, the mouth is rinsed with chlorhexidine solution (0.2%) for 2 min, and periodontal pockets are irrigated with chlorhexidine solution (1%). Significant reduction in pocket depth and gain in clinical attachment in patients with aggressive periodontitis up to 8 months after treatment was noted, and also, significant reduction was found in periodontal pathogens up to 8 months after therapy. 
A novel approach in the treatment of aggressive periodontitis is the administration of agents that modulate the host response. The use of sub-antimicrobial dose doxycycline (SDD)  may help to prevent the destruction of the periodontal attachment by controlling the activation of matrix metalloproteinases, especially collagenase, from both the infiltrating cells and resident cells of the periodontium, primarily neutrophils. SDD, as an adjunct to repeated mechanical debridement, resulted in clinical improvement in patients with generalized aggressive periodontitis.
Other agents such as CMT, flubiprofen, indomethacin, and naproxen may reduce inflammatory mediator production. Further research is awaited for the use of such agents.
Treatment of aggressive periodontitis should start with scaling and root planing in combination with systemic antibiotics. It is recommended  that (i) initiation of antibiotic therapy is done 24 h before starting scaling and root planing and (ii) the root planing is performed over the short time period during which the antibiotic is prescribed.
A 4-6 week re-evaluation interval seems to be valid for a patient with aggressive periodontitis. If, however, there is no significant response to initial therapy, the clinician may choose to repeat sub-gingival scaling with a different antibiotic regimen. If the response to initial therapy supports proceeding to the surgical phase, systemic antibiotic should be prescribed with the patient being instructed to start taking the antibiotic approximately 1 h before surgery.  Chlorhexidine rinses should be prescribed and continued for several weeks to aid healing and augment plaque control.
Ultimately, the clinician's success in treating patients with aggressive periodontitis depends mostly on the maintenance program. Monthly maintenance is recommended for the first 6 months, after completing active treatment, and then bi-monthly maintenance for six more months. If the patient is stable during this first year, maintenance intervals can be extended up to 3 months. Sub-gingival scaling in combination with local delivery of antibiotics is a good way to manage isolated sites of recurring disease, while full mouth scaling and systemic antibiotics or host modulation therapy can be used to treat a generalized recurrence. 
Aggressive periodontitis is a challenge for the clinician because it is infrequently encountered and the predictability of treatment success varies from one patient to another. These unusual entities often do not respond well to conventional therapy owing to the complex nature of the disease. The best treatment for these patients appears to be a combination of conventional treatment with antimicrobial therapy (systemic and/or local delivery) and close follow-up care. Adjunctive host modulation, although only an emerging are of interest, may prove to be promising in the treatment of patients with aggressive periodontitis.
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