During the past two decades, dentists and microbiologists have embraced periodontal antibiotic therapy as a powerful adjunct to conventional mechanical debridement for therapeutic management of the periodontal diseases,[12] as the evidence for bacterial specificity in periodontitis has accumulated and strengthened. Antibiotics, are defined as naturally occurring or synthetic organic substances that, in low concentrations, inhibit or kill selective microorganisms.[1]

The concept of antibiotic periodontal therapy centers upon the pathogenic microbiota, the patient, and the drug.[3] There are numerous antibiotics that could be employed to treat periodontal infections, but it is often unclear which antibiotic would provide the greatest benefit to a patient with a specific periodontal infection, with minimal adverse effects.

The discussion below concerns with the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy.

Mechanical and surgical treatment combined with proper oral hygiene measures can arrest or prevent further periodontal attachment loss in most individuals by reducing total supra-subgingival bacterial mass.[4] However, despite diligent dental therapy, some individuals continue to experience periodontal breakdown, may be due to the ability of major periodontal pathogens like Porphyromonasgingivalis, Aggregatibacteractinomycetemcomitans, Fusobacterium-nucleatum, Treponemadenticola, bacteroids, to invade periodontal tissues or to reside in furcations or other tooth structures outside the reach of periodontal instruments, or due to poor host defense mechanisms.[4] In addition, the putative periodontal pathogens (“red complex”) tend to reside in the section of the biofilm attached to the epithelial surface of the periodontal pocket and the patient cannot reach this site during the oral hygiene efforts.[5]

The prime candidates for systemic antimicrobial therapy are those patients exhibiting attachment loss after seemingly adequate conventional therapy, or patients with aggressive forms of periodontitis or associated with predisposing medical conditions or refractory periodontitis.[6] Patients with acute or severe periodontal infections (periodontal abscess, acute necrotizing gingivitis/periodontitis) may also benefit from antibiotic therapy.[3]

Systemic periodontal antibiotic therapy aims to reinforce mechanical periodontal treatment and to support the host defense system in overcoming the infection by killing subgingival pathogens that remain after conventional mechanical periodontal therapy.[4] The susceptibility of bacteria to antibiotics may be the key to the efficacy of systemic antibiotics in the treatment of periodontal diseases.Few chemotherapeutic agents can also reduce collagen and bone destruction through their ability to inhibit the enzyme collagenase. Patients with gingivitis or stable adult periodontitis usually respond well to mechanical periodontal therapy and derive little or no additional benefit from antibiotic therapy.

The clinical diagnosis and situation dictate the need for possible antibiotic therapy as an adjunct in controlling active periodontal disease as the patient's diagnosis can change overtime.[5]

After having established the need for using an antibiotic in a patient, it is often difficult to decide which one to choose from the large number available. The factors governing the decision for selection of antibiotics are:[9]

Age of patient: It may affect pharmacokinetics of many antibiotics e.g. tetracyclines accumulate in the developing teeth and bone.

The microbial composition of subgingival plaque varies considerably from patient to patient.

The description of the Gram stain reaction and the anaerobic requirement of the infectious periodontal microbiota provided the first guidelines for selection of antimicrobial therapy.

Delineation of the type of periodontal infection (exogenous/endogenous) may be important in selecting a proper strategy for antimicrobial therapy in periodontics.[4]

Two critical factors should be specifically considered in selecting a systemic antibiotic in periodontal therapy:[10] Gingival fluid concentration and Minimum inhibitory concentration (MIC).

The gingival fluid concentration (C_GCF) provides information on the peak levels achieved by systemic delivery at the primary ecological niche for periodontal pathogens, the periodontal pocket.

100 (C_GCF/MIC₉₀) = antimicrobial activity expressed as a percentage for each antibiotic and each organism.

Antibiotics that can achieve 90% inhibition of growth of an organism appear on the 100% line. The most effective antibiotics for treatment of a particular periodontal pathogen are those that equal or exceed the 100% value.

Periodontal diseases in which antibiotics can be used:

Chronic periodontitis: Antibiotic therapy is usually recommended for patients showing progressive periodontal breakdown even after conventional mechanical treatment, patients not responding to periodontal therapy (refractory periodontitis) and patients with recurrent disease.[14] Reviewing pertinent literature[2–5] use of following antibiotics has been suggested:

Tetracycline, Doxycycline, Metronidazole, Clindamycin, Amoxicillin + Clavulinic acid (Augmentin), Azithromycin, Metronidazole + Amoxicillin, Spiramycin.

Employ high doses for a short duration: Antibiotic success depends on maintaining the blood and tissue concentrations above the minimal inhibitory concentration for the target organism. High concentrations are more critical with aminoglycosides, metronidazole and quinolones (concentration-dependent antibiotics), whereas prolonged exposure of the organism to the antimicrobial agent is more critical with the beta lactams (time-dependent antibiotics).

Eight principle antibiotic groups have been extensively evaluated for treatment of the periodontal diseases; tetracycline, minocycline, doxycycline, erythromycin, clindamycin, ampicillin, amoxicillin and metronidazole.[10] A brief review of these drug groups is as follows:

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 or metronidazole) is given concurrently. When both types of drug are required, they are best given serially, not in combination, to avoid unfavourable interaction yet derive the benefit of both.[5]

In one such study, six patients with recurrent progressive periodontitis were given the usual adult dosage of doxycycline for 4 days followed by amoxicillin with clavulanate for 5 days. Five similar patients were given doxycycline alone for 10 days. After 25 weeks, patients receiving the sequential combination had significantly greater pocket depth reduction than those receiving doxycycline alone.[2]

In another study, all patients with recurrent periodontitis received regular bimonthly scaling and sequential dose of doxycycline and metronidazole. In the combined antibiotic group, 9% were observed to have recurrent periodontitis, whereas 42% of the placebo group showed signs of recurrent disease. Although these differences appear statistically significant, by 7 months after metronidazole, no difference in microbiota between groups could be detected.[2]

A combination of metronidazole and amoxicillin (MA) has shown to be an effective antibiotic regime to combat Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis-associated periodontal infections.[20]

One important clinical finding in a study by Winkel et al.,[21] was the observation that patients with subgingival P. gingivalis at baseline who were treated with metronidazole+amoxicillin showed approximately half the number of >5 mm pockets after therapy compared with P. gingivalis positive patients treated with placebo. Guerreo et al.[22] used a comparable treatment protocol in patients with aggressive periodontitis and showed significantly better improvement of all periodontal parameters in the antibiotic treated patients compared to placebo treated subjects 6 months post-treatment.

These studies have revealed that, in chronic as well as in aggressive periodontitis, the antibiotics result in better resolution of the periodontal inflammation, better probing depths, and attachment loss reduction.

Metronidazole and clindamycin appear to be more efficient in eradicating the anaerobic periodontopathic bacteria than doxycycline or mechanical therapy alone.[23]

Metronidazole ciprofloxacin combination is effective against A. actinomycetemcomitans. Metronidazole targets obligate anaerobes, and ciprofloxacin targets facultative anaerobes. This is a powerful combination against mixed infections. Studies of this drug combination in the treatment of refractory periodontitis have documented marked clinical improvement.[24]

Patients having uncontrolled diabetes, organ transplantation, bone marrow transplantation, prosthetic joint replacement, leukemia, neutropenia, thrombocytopenia are at greater risk of developing infection after dental procedures due to immunosuppression or decreased number of immune cells.[2526] Chronic renal disease patients also need antibiotic prophylaxis to prevent endarteritis of the arteriovenous fistula or shunt.[25] To prevent infective endocarditis in patients having previous history of infective endocarditis, prosthetic cardiac valves, major congenital heart disease (tetralogy of Fallot, transposition of great arteries, surgically constructed systemic pulmonary shunts or conduits), acquired valvular function (e.g., rheumatic heart disease), hypertrophic cardiomyopathy, mitral valve prolapsed with valvular regurgitation, thickened leaflets or both, antibiotic prophylaxis is recommended.[25]

The periodontal procedures considered as high risk procedures in these patients are probing, scaling, root planing, subgingival placement of antibiotic fibers or strip, intraligamentary local anesthetic injections, prophylactic cleaning of teeth or implants with anticipated bleeding, periodontal surgery, dental implant placement.[27] Amoxicillin is used most commonly used for antibiotic prophylaxis. The recommended dosage is 2 g in adults and 50 mg/kg in children, orally one hour before procedure. For the patients who cannot use oral medication, ampicillin is given intramuscularly or intravenously at dose of 2.0 gm in adults and 50 mg/kg in children within 30 minutes before procedure. In patients allergic to penicillin, the antibiotics preferred are clindamycin (adults, 600 mg; children, 20 mg/kg orally one hour before procedure), Cephalexin or cefadroxil (adults, 2.0 g; children, 50 mg/kg orally one hour before procedure), Azithromycin or clarithromycin (adults, 500 mg; children, 15 mg/kg orally one hour before procedure). The patients allergic to penicillin and unable to take oral medications are given clindamycin (adults, 600 mg; children, 15 mg/kg IV one hour before procedure) or cefazolin (adults, 1.0 g; children, 25 mg/kg IM or IV within 30 minutes before procedure).[27]

The clinical reasons for antibiotic failure are as follows:[11]

Inappropriate choice of antibiotic

It has been established that systemic antibiotics can significantly enhance the effects of mechanical periodontal therapy in conjunction with measures that improve the oral hygiene. Clinical studies of systemic antibiotic therapy in adult periodontitis, refractory periodontitis, aggressive periodontitis patients have been given in Table 3. As suggested by Herrera et al.[6] and Haffajee et al.[8] the mean “gain” in attachment of 0.3-0.4 mm may appear small, but it was based on change throughout the mouth including sites with shallow probing depths whose post-therapy improvement would be expected to be modest. As a bench mark, periodontitis subjects monitored after treatment and on supportive periodontal therapy for about 12 years only experienced an average annual full mouth mean attachment loss of 0.042 mm (normal susceptibility subjects) to 0.067 mm (high susceptibility subjects).[28] Thus, attachment level “gain” of 0.3 mm would be equivalent to reversing 4-7 years of disease progression in a treated and maintained population.[8]

All the antibiotics used in periodontal therapy, inhibit growth of the major periodontal pathogens P. gingivalis, C. rectus and Capnocytophaga. In direct contrast, none are particularly effective in the inhibition of E. corrodens (minocycline and doxycycline being best). Minocycline appears to be the most effective antibiotic, which achieves levels that should be completely inhibitory (antibiotic activity = 600%) to most of the periodontal pathogens but may inhibit the growth of beneficial species as well.[10] Amoxicillin appears almost as effective as minocycline. Tetracycline, the most commonly used antibiotic, but appears to be a relatively poor choice for A. actinomycetemcomitans infections, for which it has been used most commonly. Erythromycin appears to be a poor choice for any pathogenic oral infection. Metronidazole is uniquely effective in treating Selenomonassputigena and Peptostreptococcus infections and equal to minocycline in treating Fusobacterium infections.

Periodontal infections can involve a variety of pathogens with different antimicrobial sensitivities and resistance patterns. In periodontal infections, tissue barriers and biofilms should be removed, by mechanical debridement prior to or with antibiotics. The periodontal disease status and the antimicrobial regimen must be determined carefully to succeed with antimicrobial periodontal therapy. Unless antimicrobial agents against periodontal disease are used intelligently, we may soon face a new breed of oral microorganisms with heightened defenses that will ensure the survival of the species, allows for greater pathogenicity and transfer genetic material coding for increased virulence and antibiotic resistance to other oral and nonoral microorganisms.