Anti-Infective Agents in Periodontal Treatment

From Medscape Dentistry & Oral Health Jorgen Slots, DDS, DMD, PhD, MBA Posted: 09/15/2011 Periodontitis is a polymicrobial infectious disease associated with specific bacterial species[1] (Table 1) and herpesviruses.[2] The primary goal of periodontal therapy is to achieve a periodontal environment free of infectious pathogens. Anti-infective periodontal treatment includes mechanical pocket debridement (scaling and root planing) to remove dental calculus, periodontal pocket irrigation with potent antiseptics, systemic antibiotics for advanced disease, and proper patient self-care. Pharmacotherapeutics targeting subgingival microorganisms can significantly enhance treatment outcomes. However, because porous subgingival calculus comprises a protective reservoir for bacterial survival during anti-infective therapy, meticulous scaling and root planing must precede antiseptic and antibiotic periodontal treatment. The antimicrobials recommended here are readily available throughout the world, have been used in periodontal therapy for decades, offer significant benefits for individuals with limited financial resources, and are well accepted by most dental professionals and patients. Antiseptic Agents in Periodontal Disease An increase in antibiotic-resistant bacteria has created interest in using inexpensive, safe, and highly bactericidal/virucidal antiseptics in periodontal therapy. Antiseptics attack multiple components of infectious agents, practically eliminating the risk for development of resistance, and do not interact with prescription medications. Antiseptics are particularly valuable in the treatment of biofilm infections, which may be unresponsive to even high concentrations of antibiotics. Moreover, because the contents of inflamed periodontal pockets are emptied into the oral cavity every 90 seconds, and relatively small amounts of antimicrobial agents are applied subgingivally, the risk for antiseptics entering the gingival tissue and causing systemic damage is virtually nonexistent. This high degree of safety allows frequent and broad use of antiseptics in periodontal treatment. Povidone-Iodine Aqueous (Lugol's iodine) and tincture (iodine in alcohol) solutions of iodine have been employed as dental antiseptics for more than 150 years, but the early iodine formulations caused surface staining and irritation of mucosa and skin. Iodophors (iodine-releasing agents) developed in the 1950s were solutions of iodine complexed with an organic carrier that largely overcame the negative aspects of iodine treatment. The most common commercial form of povidone-iodine (Betadine® or generic equivalent) is a 10% solution in water, yielding 1% (10,000 ppm) available iodine. Povidone-iodine can give rise to allergic reactions, including itching, burning, and reddening and blistering in the area of application, so a patient's history of allergy to iodine or shellfish must be evaluated. Prolonged iodide intake can inhibit thyroid hormone synthesis and cause goiter, myxedema, or hyperthyroidism; therefore, povidone-iodine should not be used in patients with thyroid dysfunction, pregnant woman, infants, or in routine patient self-care. Povidone-iodine kills in vitro all major periodontopathic bacteria within 15 to 30 seconds and exhibits a wide virucidal spectrum, covering both enveloped (eg, herpesviruses) and non-enveloped viruses. Several studies have shown a measurable improvement in periodontal status after treatment with full-strength povidone-iodine.[4] A study from Sweden[5] showed that patients who received a whole-mouth application of povidone-iodine at the time of initial therapy exhibited less periodontitis for up to 13 years after treatment. Povidone-iodine lavage together with thorough debridement of necrotic tissue has arrested the progression of noma in HIV-infected patients.[6] Of potentially great clinical significance, povidone-iodine can kill the major cariogenic bacterium Streptococcus mutans, and caries-prone children who received a povidone-iodine application to their entire dentition every 2-3 months experienced a marked reduction in new caries lesions compared with control children.[7] Povidone-iodine used in periodontal treatment is applied subgingivally using, for example, a 3-mL endodontic syringe with a 23-gauge cannula that has a blunt end and side ports. The cannula is inserted into the base of the periodontal pocket to ensure maximum drug delivery. A single course of subgingival irrigation of the entire dentition takes about 1.5 minutes and is repeated at least 3 times for a total application time of 5-10 minutes. Sodium Hypochlorite Sodium hypochlorite (NaOCl) is a highly active cytotoxic oxidant recognized to be among the most potent antiseptic and disinfectant agents against bacteria, fungi, and viruses. Sodium hypochlorite occurs naturally in human neutrophils and monocytes/macrophages therefore, it does not evoke allergic reactions; it is not a mutagen, carcinogen or teratogen; and it has a century-long safety record. Dilute sodium hypochlorite has no contraindications. Sodium hypochlorite is available globally at exceptionally low cost as household bleach in concentrations of 5%-6%. Sodium hypochlorite has been used as an antiseptic agent in dentistry for more than a century and remains a widely used root canal irrigant at concentrations ranging from 1.0%-5.25%. Sodium hypochlorite rinsing exerts broad antimicrobial activity against experimental oral biofilms and reduces biofilm by 80-fold compared with water. Dilute sodium hypochlorite rinse (0.5%) has produced a 47% greater reduction in dental plaque mass compared with water rinsing.Low gingivitis scores were maintained around teeth receiving sodium hypochlorite rinse, whereas the gingivitis score increased by 50% in control teeth The American Dental Association Council on Dental Therapeutics has designated dilute sodium hypochlorite a "mild antiseptics mouth rinse" and suggested its use for direct application to mucous membranes.The lowest concentration of sodium hypochlorite solution that reliably inactivates bacteria in vitro is 0.01%. Patients are advised to use an oral irrigator for subgingival application of sodium hypochlorite at a concentration of 0.5%. This is equivalent to 10 mL (2 teaspoonfuls or two thirds of a tablespoon) of 6% household bleach in 125 mL (one half glass) of water. Patients are also advised to rinse orally with 0.2% sodium hypochlorite for 30 seconds, 2 or 3 times per week. This is equivalent to 8 mL (2 reduced teaspoonfuls) of 6% household bleach in 250 mL (a full glass) of water. More frequent rinsing may produce a brown-black extrinsic discoloration of the teeth. Diluted hypochlorite solutions gradually lose strength, so fresh solutions should be prepared for each use. Chlorhexidine Chlorhexidine, a bisbiguanide, has been an important oral antiseptic for more than 40 years, and numerous studies and meta-reviews have confirmed its antiplaque and antigingivitis effects. The ability of chlorhexidine to adhere to the dental pellicle and oral mucosa prolongs its antiplaque effect. Chlorhexidine gluconate is used in dentistry as a 0.12%-0.2% mouthwash applied in a volume of 15 mL for 30 seconds. Low-cost generic chlorhexidine in concentrations of 2% or higher can be diluted in water to the desired concentration for oral use. Chlorhexidine is inactivated by organic serum compounds in the gingival crevice fluid, and subgingival placement produces little change in microbial and clinical variables.As the antimicrobial action of the cationic chlorhexidine is neutralized by anionic compound surfactants in toothpastes, chlorhexidine should not be used in conjunction with toothbrushing. A major disadvantage of chlorhexidine is its propensity to dark stain tooth surfaces. Dark staining gaps along the margin of tooth-colored restorations may reflect into the filling material and necessitate replacement of affected restorations. Antibiotics in Periodontitis Systemic antibiotic therapy for periodontitis aims at reducing or eradicating specific periodontopathic bacteria that are not readily reached by topical therapy, such as pathogens in gingival tissue, in furcation defects, at the base of periodontal pockets, and on the tongue, tonsils and buccal mucosa. The selection of effective and safe antibiotics can be challenging because periodontitis lesions usually harbor a constellation of periodontopathic bacteria that have diverse susceptibility profiles. The tradition in dentistry is to treat empirically (eg, institute antibiotic therapy on the basis of the "best estimate" of the most probable pathogen or pathogens and the usual antibiotic susceptibility pattern of the suspected pathogen or pathogens). Microbiological testing with antimicrobial susceptibility profiling allows dentists to move from a trial and error approach to the more predictable targeted therapy, but susceptibility testing depends on complex and relatively expensive culture methods in a reference laboratory. Antibiotic combination therapy with 2 antibiotics is used to take advantage of different mechanisms of action and to expand the spectrum of antimicrobial activity. Amoxicillin-metronidazole (250 mg amoxicillin-375 mg metronidazole, 3 times daily for 8 days) is the most common antibiotic combination in periodontics. Ciprofloxacin-metronidazole (500 mg of each, twice daily for 8 days) is indicated for periodontitis involving a mixture of enteric gram-negative facultative rods and anaerobic bacteria. Enteric gram-negative facultative rods are particularly prevalent in periodontal sites of older individuals and immunocompromised patients. Ciprofloxacin-metronidazole combination therapy is also a valuable alternative for penicillin-allergic patients. Metronidazole exerts activity against Clostridium difficile and thus reduces the risk for pseudomembranous colitis. Valacyclovir (500 mg, twice daily for 10 days) may be prescribed for patients with severe periodontitis, which is virtually always associated with a herpesvirus infection. The dosing recommendations are for healthy adults with normal weight and must be adjusted for body size to ensure optimal therapeutic effectiveness and safety. Interactions with other medications, toxicity, and hypersensitivity may restrict antibiotic use in individual patients. Tetracycline HCl, doxycycline HCl, and minocycline HCl embedded in various delivery systems have been marketed commercially for direct placement into the periodontal pocket. The usefulness of topical antibiotics in periodontal treatment is questionable.The chief drawbacks of topical antibiotic therapy are an insufficient range of antimicrobial activity for even broad-spectrum antibiotics, a modest and transient clinical effect, possible development of resistant bacteria, adverse host reactions, and high acquisition costs. Topical antibiotic agents are a less desirable choice than the topical use of broad-spectrum, low-cost antiseptic agents with low potential for adverse reactions. Conclusion Mechanical debridement combined with subgingival povidone-iodine application in the dental office and sodium hypochlorite irrigation for patient self-care are valuable antimicrobial treatments in the management of virtually all types of periodontal disease. Systemic antibiotics or periodontal surgery may be required in the treatment of advanced periodontitis.