Antimicrobials

The Ins and Outs of Periodontal Antimicrobial Therapy

Michael G. Jorgensen, DDS, Jørgen Slots, DDS, DMD, PhD, MS, MBA

Copyright 2002 Journal of the California Dental Association.

A multifaceted antimicrobial approach is necessary for the successful management of destructive periodontal disease. Effective antimicrobial periodontal therapy aims to overwhelm periodontal pathogens with aggressive initial therapy and prevent previously suppressed pathogens from rising up anew through daily oral hygiene measures and frequent professional cleaning. Current antimicrobial periodontal therapy employs mechanical debridement performed with and without surgery, antibiotics, and antiseptics. Subgingival irrigation with povidone-iodine at the dentist’s office and subgingival irrigation with dilute sodium hypochlorite for home-care constitute effective, safe, and affordable periodontal antimicrobial therapy. This article describes theoretical and practical guidelines for implementing rational and cost-effective antimicrobial principles in the management of periodontal disease.

Periodontal disease is probably the most widespread inflammatory disorder in humans, affecting virtually all adults throughout the world. Severity of periodontal disease ranges from mild gingival inflammation to advanced periodontal attachment loss, sometimes resulting in loss of teeth. Historically, a predominantly mechanical approach to treatment has been employed; and outcomes have often been disappointing, due to clinicians’ inability to adequately control periodontal pathogens and patients’ inability or unwillingness to comply with measures necessary to prevent recurrence of disease. Use of antimicrobial agents in periodontal treatment has often been somewhat haphazard and empirical; however, there is evidence that the addition of appropriate antimicrobial therapy to traditional periodontal treatment may substantially enhance clinical outcomes and reduce the need for costly surgical procedures. At the University of Southern California School of Dentistry, a comprehensive scientifically based protocol has been developed that emphasizes rational uses of antimicrobial agents in periodontal therapy. It is the aim of this article to evaluate current periodontal antimicrobial therapies with respect to efficacy, safety, and affordability. A proficient cost-effective antimicrobial periodontal treatment may offer populations who are currently unable to receive adequate care due to lack of financial resources a practical and valuable means of maintaining a functional periodontium and dentition for a prolonged period.

Periodontal Microbiota

Destructive periodontal disease is an infectious process and, hence, may best be managed by anti-infective intervention. Causes may include nonspecific bacterial plaque, as in gingivitis and mild forms of chronic (adult) periodontitis, or specific bacterial infections, as in aggressive (early onset) periodontitis. Both specific and nonspecific dental plaque microorganisms colonize tooth surfaces as biofilms, a phenomenon that makes treatment of these infections particularly challenging.¹ Biofilms are defined as sessile communities of microbial cells that develop on surfaces in aquatic ecosystems. Biofilm microorganisms reside as highly structured populations and assume a phenotype that is clearly different from that of their free-living counterparts. The biofilm concept has several clinical implications and is particularly important in understanding the killing and resistance of oral microorganisms. The biofilm phenotype shows a remarkable resistance to antibiotics, biocides, and components of host defenses that are effective in controlling planktonic cells. To overcome the protective effect of biofilms, it is important to disrupt subgingival plaque at the time of initiation of antimicrobial therapy, either mechanically (scaling and root planing), chemically (dilute sodium hypochlorite irrigation), or by using a combination of these approaches.

Another complicating factor in managing some periodontal diseases is the invasion of gingival tissues by periodontopathic microorganisms. Actinobacillus actinomycetemcomitans is a tissue-invading organism that cannot always be removed by mechanical debridement, topical antibiotics, or antiseptics, but can be eradicated by a properly selected systemic antibiotic regimen.² Certain anatomic variations, such as narrow furcations, root concavities, and close root proximity severely limit the effectiveness of mechanical therapy; and in these situations systemic antibiotics arriving via crevicular fluid may be a valuable adjunctive treatment. Periodontitis lesions that are recalcitrant to conventional periodontal therapy often harbor a variety of periodontal pathogens that have escaped the cleaning efforts of the dentist and the patient (Table 1). However, refractory periodontitis can often be successfully treated using a combination of systemic antibiotics and locally delivered antiseptics.³

Clearly there are advantages to augmenting traditional mechanical periodontal therapy with properly selected antimicrobial agents. Currently there are a wide variety of systemic and locally delivered products available to the dental practitioner. These will be reviewed and guidelines will be presented to assist clinicians in selecting appropriate treatment strategies for their patients.

Systemic Antibiotics

Routine use of systemic antibiotics in treating chronic (adult) periodontitis is not recommended; it is unnecessary and is likely to increase the development of resistant strains of bacteria.⁴ Selection of antibiotics in clinical practice is either empirical or based upon the results of microbiological tests. Empirical antibiotic therapy may be used for periodontal diseases with known microbial etiologies, such as acute necrotizing ulcerative gingivitis that is caused by anaerobic organisms that can be cured by metronidazole, and early localized juvenile periodontitis that mostly involves A. actinomycetemcomitans that can be eradicated by systemic amoxicillin-metronidazole combination therapy. However, even the most careful clinical examination cannot delineate the likely microbial pathogens in most types of periodontitis nor determine their susceptibility to various antibiotics. Microbiological analysis of subgingival plaque provides valuable information that will facilitate accurate diagnosis and optimal treatment planning (Figures 1 and 2). Fortunately, therapeutic antibiotic therapy in periodontics can be deferred until the results of culture, nucleic acid-based diagnostic tests, and antimicrobial susceptibility determination are available. Recent articles outline criteria for selection of antibiotics and the value of microbiological testing in periodontal treatment.^5,6

Systemic antibiotics may be used singly or in combinations. Single-agent antibiotic therapy in current periodontics includes metronidazole (500 mg/3x daily/for 8 days), clindamycin (300 mg/3x daily/for 8 days) and ciprofloxacin (500 mg/2x daily/for 8 days) (all adult dosages). Common combination therapy in periodontics includes metronidazole and amoxicillin (250 mg each/3x daily/for 8 days), and metronidazole and ciprofloxacin (500 mg each/2x daily/for 8 days). Food does not influence the bioavailability of most oral antimicrobial agents, with the exception of tetracyclines, quinolones, and azithromycin. These three groups of antimicrobial drugs should be given one hour before or two hours after food intake. When a choice must be made between equally effective antibiotics, it is prudent to consider the financial cost of therapy (Table 2).

A low dosage of doxycycline (20 mg) taken twice daily has the potential to inhibit mammalian collagenases and has been suggested as an aid in controlling periodontitis.⁷ However, the postulated absence of antimicrobial activity from this therapeutic approach has been questioned,^8,9 and therefore potential problems with antibiotic resistance and development of hypersensitivity may need to be addressed. Compared to placebo medication, low-dosage doxycycline treatment of periodontal sites probing greater than or equal to 7 mm gives rise to only about 0.48 mm additional reduction in probing pocket depth and 0.38 mm additional gain in clinical attachment level.¹⁰ Even if low-dose doxycycline might temporarily retard the progression of periodontitis, long-term efficacy and safety of the therapy has not been established. It is troublesome that minimal resolution of gingival bleeding occurs even after nine months of daily doxycycline administration.¹⁰ Since repeated gingival bleeding is one of the most useful clinical predictors of future periodontal breakdown,¹¹ long-term follow-up data are warranted on the periodontal status after the low-dose doxycycline therapy has been discontinued.

Locally Delivered Antibiotics

Controlled-release devices that contain tetracycline-HCl, doxycycline, minocycline, metronidazole, or ofloxacin for direct pocket placement are commercially available in various countries. In controlled-release drug delivery, the antimicrobial agent is released during an extended period of time by zero-order drug-release kinetics.¹² The usefulness of topical antibiotic therapy in periodontics is controversial. Most published studies have monitored the effect of controlled drug delivery on clinical variables characteristic of gingivitis and not necessarily of periodontitis, and the adjunctive or alternative role of topical antibiotic therapies in short- and long-term management of periodontal disease has not been defined either.

Table 3 describes clinical outcomes of some commercial controlled-release devices for antimicrobial periodontal therapy. As an adjunct to scaling and root planing, subgingival placement of minocycline-loaded microcapsules has been reported to enhance reduction in bleeding upon probing.¹³ Topical minocycline, however, is likely to be ineffective in eradicating tissue-invading A. actinomycetemcomitans from periodontal pockets and may even promote subgingival overgrowth of minocycline-resistant yeasts and various enteric rods.¹⁴ In patients with moderate to severe chronic periodontitis, application of 2 percent minocycline hydrochloride gel failed to provide any additional probing depth reduction or clinical attachment gain when used as an adjunct to scaling and root planing.¹⁵ Locally applied tetracycline fibers have been shown to have some clinical benefits up to six months following therapy when used in conjunction with scaling and root planing;¹⁶ however, follow-up evaluation after five years revealed no benefit compared to scaling and root planing alone.¹⁷ Considering potential problems with selectivity of antimicrobial action and possibly development of resistant bacteria and adverse host reactions as well as high medication costs, topical antibiotic therapy seems to constitute an inferior choice to topical use of a low-cost, broad-spectrum antiseptic agent with low potential for adverse reactions.

Locally Delivered Antiseptics

Mechanical root debridement to remove dental calculus is important in periodontal therapy but is frequently inadequate in curing severe periodontal infections.²⁵ To augment mechanical debridement, topical antiseptics may be used to kill periodontal pathogens during initial therapy and to suppress their repopulation during maintenance therapy.²⁵ Antiseptics are chemical agents that have the ability to inactivate the growth of a large range of microorganisms in or on living tissue. To have therapeutic value, pharmaceuticals must be delivered at an effective concentration and for an adequate length of time. Gingival crevicular fluid flow averages 20m l/hour and increases with gingival inflammation,²⁶ which is equivalent to a turnover rate of 40 times per hour in a medium-sized periodontal pocket with a volume of 0.5 m l.²⁷

Subgingival antimicrobials can be administered either by noncontrolled delivery for fast-acting pharmaceuticals or by controlled drug-delivery devices for slow-acting agents. Povidone-iodine is able to kill microorganisms rapidly enough to overcome the drug-diluting effect of gingival crevicular fluid and is effective when delivered by subgingival irrigation, provided a contact time of at least five minutes is achieved.²⁸ The American Heart Association suggested that antiseptic mouthrinses such as povidone-iodine applied immediately prior to dental procedures might reduce the incidence or magnitude of bacteremia.²⁹ Blue povidone-iodine stains on starched linen will wash off with soap and water. Other iodophore stains can be readily removed with a 5 percent solution of sodium thiosulfate.

Sodium hypochlorite is a strong oxidizing agent that possesses numerous attractive properties for antiseptic use, including rapid bactericidal action, ease of use, and very low cost. Irrigation with dilute (0.5 percent) sodium hypochlorite solution has been shown to cause significantly greater and longer-lasting reduction in plaque and gingivitis than irrigation with water.³⁰

In contrast, chlorhexidine digluconate mouthrinses at concentrations of 0.1 percent to 0.2 percent, which have a long history of use in controlling supragingival plaque and gingivitis,³¹ may require controlled-release delivery to exert effective killing of subgingival microorganisms.³² Also, chlorhexidine tends to be more bactericidal for gram-positive organisms populating supragingival plaque than for gram-negative species inhabiting periodontal pockets.³³ Recently, a controlled local delivery system containing 2.5 mg of chlorhexidine gluconate incorporated into a biodegradable chip of hydrolyzed gelatin was introduced for subgingival antimicrobial treatment (Periochip, Astra Pharmaceuticals, Westborough, Mass.). Initial studies found that the use of the chlorhexidine chip in conjunction with scaling and root planning had some potential to reduce periodontal probing depth, clinical attachment loss, and bleeding on probing.^34,35 However, a recent prospective clinical study that evaluated changes in levels of periodontal pathogens before and after scaling and root planning with and without adjunctive use of the chlorhexidine chip showed no microbiological benefits to placement of the chlorhexidine chip following thorough mechanical debridement.³⁶

Clinical Protocol for Antimicrobial Therapy

Prior to developing a suitable treatment plan, it is essential to establish a complete and accurate assessment of the patient’s oral/periodontal and medical conditions. First, it is important to determine the chief complaint or the patient’s reasons for seeking treatment. These could include pain, swelling, gingival bleeding, impaired function, unsatisfactory esthetics, or a combination of these reasons. Next, the medical status of the patient must be reviewed and vital signs recorded. This will determine the patient’s suitability for dental treatment and identify any special precautions that must be taken, such as premedication for prevention of bacterial endocarditis.²⁹ Medications with the potential to adversely effect gingival health include phenytoin, cyclosporin, and various calcium channel blockers.³⁷ Poorly controlled diabetes and smoking have been reported to predispose patients to periodontal disease and adversely effect response to treatment.^38,39 Anticoagulant therapy, including low-dose aspirin, may need to be modified to ensure adequate hemostasis during and after surgical procedures.^40,41 Patients having compromised host defense mechanisms may require more frequent and comprehensive antimicrobial periodontal therapy. An appropriate dental examination including periodontal pocket depth measurements will lead to an accurate diagnosis. Periodontal conditions should be classified under one of the following three general categories: gingivitis, chronic periodontitis, or aggressive periodontitis. Figure 3 describes how each of these disease categories can be effectively treated.

Plaque-Induced Gingivitis

Oral hygiene instruction should educate and motivate the patient to accomplish effective daily plaque removal. Soft and hard deposits and stains are removed by scaling and polishing. Disinfection of subgingival sites is performed by repeated irrigation with 10 percent povidone iodine (Betadine, Perdue Frederick Co., Norwalk, Conn.) with a contact time of at least five minutes. Irrigation is performed using a 3 cc disposable syringe with a 23 gauge blunt-tipped cannula. Iodine should not be used during pregnancy or nursing, nor in patients with thyroid disease or sensitivity to iodine. For patients who should not be treated with iodine, 0.12 percent or higher concentrations of chlorhexidine gluconate may be used as an irrigant, though it is less effective due to protein binding with crevicular fluid and blood. Dilute sodium hypochlorite may also be used as a subgingival antiseptic. For most gingivitis patients, six months is a suitable recall interval; patients who require additional motivation for plaque control may need to be seen more often.

Chronic Periodontitis

In addition to daily plaque removal, patients who have experienced loss of periodontal attachment require more extensive debridement. This is accomplished initially by scaling, root planing, and subgingival irrigation with 10 percent povidone iodine. Approximately six weeks after initial debridement, periodontal conditions are re-evaluated. If no probing depths are greater than 5 mm, gingival bleeding is not seen, and plaque control is effective, the patient is scheduled for periodontal recall in four months. If probing depths greater than 5 mm or bleeding remain, surgical therapy or referral to a periodontist should be considered. Surgical treatment will provide improved access for debridement and a reduction in probing depths. Additional re-evaluation is performed in three to six months. If at that time, no probing depths are greater than 5 mm, bleeding is not seen, and plaque control is effective, the patient is scheduled for periodontal recall in three to four months. If probing depths greater than 5 mm remain or repeated bleeding is seen, microbial analysis should be performed followed by repeated mechanical debridement, subgingival irrigation with 10 percent povidone iodine, and prescription of systemic antibiotics guided by the results of microbial analysis. An additional re-evaluation is performed in approximately six weeks. If probing depths are then reduced and bleeding has subsided, the patient is scheduled for recall in three months.

Aggressive Periodontitis

It is especially important to consider microbiological testing and appropriate use of antimicrobial agents when treating patients with aggressive periodontitis. Subgingival sampling should be performed prior to any mechanical debridement. As in cases of gingivitis and chronic periodontitis, oral hygiene instruction should be an integral part of each appointment. Scaling, root planing, and subgingival irrigation with 10 percent povidone iodine is generally performed in several appointments. After completion of the last session of scaling and root planing, systemic antibiotics may be prescribed based on the results of microbial analysis. If microbial analysis is not available, prescribing the combination of amoxicillin and metronidazole, 250 mg each, three times daily for eight days, will be beneficial in approximately 70 percent of cases. Overgrowth of resistant pathogens may occur in some patients, however; and microbial testing is therefore strongly recommended whenever possible. Six weeks after completion of scaling and root planing, re-evaluation is performed. If probing depths are not greater than 5 mm and no bleeding is detected, the patient is scheduled for recall in three months. If probing depths greater than 5 mm remain or repeated bleeding is seen, surgical therapy or referral should be considered. Additional re-evaluation is performed in three to six months. If no probing depths are greater than 5 mm, bleeding is not seen, and plaque control is effective, the patient is scheduled for periodontal recall in three months. If probing depths greater than 5 mm or repeated bleeding are still seen, additional microbial analysis is indicated followed by further mechanical debridement, subgingival irrigation with 10 percent povidone iodine and an additional course of systemic antibiotics. The patient should be seen at least every three months, and may require even more frequent visits. In the majority of aggressive periodontitis cases, expedient, thorough treatment will result in a highly favorable response, including significant osseous repair of periodontal defects.

Antimicrobial Agents Used by the Patient

Chlorhexidine

0.12 percent chlorhexidine gluconate may be prescribed as a mouth rinse, initially used twice daily for two weeks as part of whole mouth disinfection.⁴² An additional one-week course of rinses may be prescribed at recall appointments. Staining of teeth and tooth-colored restorations frequently occurs, and long-term continuous use of chlorhexidine is not recommended.

Chlorine

The American Dental Association Council on Dental Therapeutics proposed using dilute sodium hypochlorite as a topical antiseptic for irrigation of wounds and as an antiseptic mouthrinse.⁴³ Sodium hypochlorite, 0.05 percent to 0.10 percent, may be used for oral irrigation. Patients should prepare a fresh solution for each use by placing one teaspoon of 5.25 percent sodium hypochlorite (plain household bleach) in the small (300 cc) reservoir of the oral irrigator (Waterpik Technologies, Inc., Fort Collins, Colo.). and then filling it with warm water. Concentration of the sodium hypochlorite solution can be adjusted to suit patients’ acceptance of the taste, and some patients may find one of the scented commercial bleaches more agreeable. The authors suggest performing subgingival irrigation with sodium hypochlorite two to three times per week. Subgingival plaque, being a biofilm, is particularly susceptible to sodium hypochlorite.³⁰

Fluoride

Fluorides have some antimicrobial properties, although they are not as effective as chlorhexidine or sodium hypochlorite. Use of fluoride rinses and/or fluoride gels for their anticaries properties is strongly recommended for periodontal patients, since as periodontal pathogens are eliminated or reduced, organisms responsible for root surface caries may proliferate. A 0.4 percent stannous fluoride gel can be applied with a toothbrush or delivered via a custom tray.⁴⁴

Povidone-iodine is not recommended for home care because of the risk of developing hyperthyroidism after frequent long-term usage.

Periodontal Maintenance

Maintenance care at regular intervals is essential to ensure long-term stability in treated periodontitis patients.⁴⁵ A recent publication describes current approaches to periodontal maintenance utilizing antimicrobials.²⁵ Briefly, patients are scheduled for maintenance care at intervals determined by clinical history and current conditions. Shallow probing depths (less than 5 mm) are more easily maintained than deeper periodontal pockets.

Stable periodontal conditions are associated with an absence of repeated bleeding upon gentle probing, presence of radiographic lamina dura, and an absence of periodontal pathogens in microbial analysis. Therapy in stable cases includes oral hygiene review, selective scaling, polishing, and irrigation with povidone iodine. It is important to avoid unnecessary instrumentation; root planing should be performed only in areas where deposits are detected, since the trauma inherent in thorough mechanical debridement often results in attachment loss in areas probing less than 3 mm.⁴⁶

In cases where periodontal disease activity is suspected, microbial analysis may be considered, more extensive debridement and subgingival povidone iodine irrigation are performed, systemic antibiotics may be prescribed depending upon the results of microbial analysis, and the interval between maintenance visits should be reduced. In patients showing signs of persistent disease activity, it may be necessary to consider retreatment, including surgical intervention to establish shallower, more easily maintainable probing depths.

Conclusion

Periodontal disease is an infectious process ranging in severity from mild gingivitis to advanced loss of connective tissue attachment and supporting bone. Dental plaque is a complex biofilm that forms on tooth surfaces as bacteria colonize. To establish and maintain periodontal health, this biofilm must be eliminated or markedly reduced, either by mechanical debridement, topical antiseptics (dilute sodium hypochlorite) or a combined mechanical and chemical approach.

Gingivitis and most chronic periodontitis involve nonspecific plaque and respond well to local treatment. Locally delivered antiseptics, such as povidone iodine and sodium hypochlorite, have a considerably broader spectrum of activity, exhibit fewer potential adverse effects, and are more effective and much less costly than locally applied antibiotics, especially those administered as controlled drug devices.⁴⁷

Aggressive periodontitis often involves one or more specific periodontal pathogens that may invade pocket epithelium and connective tissue; control of these infections may require use of systemic antibiotics in addition to topical antimicrobial measures. Microbiological analysis of subgingival plaque can provide information that is valuable in arriving at an accurate diagnosis and in selecting an appropriate antibiotic or combination of antibiotics.

Following successful periodontal treatment, gingival tissue may shrink, exposing root surfaces with little fluoride content. Also, as periodontal infections resolve, a shift toward a more gram-positive streptococcal microbiota may occur, resulting in increased numbers of cariogenic bacteria. Therefore, it is prudent to instruct patients to apply topical fluoride gel, with a toothbrush or via custom trays, on a daily basis.

Monitoring periodontal conditions on a regular basis will enable the clinician to intercept lapses in effective plaque control, perform additional debridement as necessary, and thereby ensure continued periodontal health. Properly managed, the vast majority of periodontitis patients can retain their dentition for a lifetime.

Authors

Michael G. Jorgensen, DDS, is an associate professor of clinical dentistry and director of predoctoral periodontics at the University of Southern California School of Dentistry.

Jørgen Slots, DDS, DMD, PhD, MS, MBA, is professor of periodontics and head of the Oral Microbiological Testing Laboratory at USC.

References

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To request a printed copy of this article, please contact/Michael C. Jorgensen, DDS, USC School of Dentistry, 925 W. 34th St., Los Angeles, CA 90089-0641.

Legends

Figure 1. Microbiological sampling kit.

Figure 2. A sterile endodontic paper point is inserted into periodontal pocket, removed after 10 seconds, placed in the vial of transport medium, and delivered to the laboratory. In one to two weeks a report is returned describing the periodontal pathogens present.

Figure 3. The three classes of periodontal conditions and their treatment.

Table 1. Periodontal putative pathogens in refractory periodontitis ^a

^a Approximate values from own unpublished studies

Table 2. Features of systemic antibiotics used in periodontal therapy.

Table 3. Reduction of probing depth in 4-7 mm pockets following periodontal therapy ^a

^a Caution must be exercised in comparing treatment studies that are noncalibrated and differ in types of patients and clinical measurement techniques