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A SIX-MONTH COMPARISION OF THREE PERIODONTAL LOCAL ANTIMICROBIAL THERAPIES IN PERSISTENT PERIODONTAL POCKETS

PRESENTED BY G.SRINIVAS 1ST YEAR PG DEPT OF PERIODONTOLOGY DATE:22/12/10

AUTHORS: D.F.KINANE M.RADVAR J PERIODONTOLOGY 1999 70;1-7.

INTRODUCTION: PERIODONTAL POCKET: The periodontal pocket, defined as a pathologically deepened gingival sulcus, is one of the most important clinical features of periodontal disease. MICROBIALS IN POCKET: Filaments, rods, and coccoid organisms with predominant gram-negative cell walls have been found in intercellular spaces of the epithelium. Porphyromonas gingivalis and Prevotella intermedia in the gingiva of aggressive periodontitis cases. Actinobacillus actinomycetemcomitans has also been found in the tissues

ANTIMICROBIAL AGENTS: For the purpose of organization, different classes of antibiotics have been divided into categories based on their bactericidal or bacteriostatic effect on various structures or macromolecules associated with the bacterial cell. These include: inhibition of cell wall synthesis (penicillins and cephalosporins) ; interference with the cell membrane; inhibition of protein synthesis (tetracyclines, macrolides and clindamycin); and interference with nucleic acid synthesis (metronidazole and quinolones).

LOCAL ANTIMICROBIAL THERAPY:(GOODSON 1989 Local delivery of antibacterial agents into periodontal pockets has been extensively developed and investigated since the late 1970s. many systems have been designed to maintain high levels of antimicrobial agents in the crevicular fluid with minimal systemic uptake. It is possible that chemical antimicrobial agents locally applied into periodontal pockets may further suppress periodontal pathogens and thereby augment the effects of conventional mechanical periodontal therapy.

Types of local antimicrobial agent therapy in periodontics 1. Personally applied (in patient home self-care) A. Nonsustained subgingival drug delivery (home oral irrigation) B. Sustained subgingival drug delivery (none developed to date) 2. Professionally applied (in dental oflice) A. Nonsustained subgingival drug delivery (professional pocket irrigation) B. Sustained subgingival drug delivery (controlledrelease device)

I Soskolne et al (1997) divides sub-gingival sustained release system based on three physical forms. Fibers tetracycline fiber (ACTISTE TM) Films / slabs -Chlorhexidine chip (PERIOCHIP TM) -Minocycline films - Otaxacin strip (PT-01 TM) Injectable systems
Doxycyline gel (ATRIDOX TM) Minocycline gel (DENTOMYCIN TM) Minocycline ointment (PERIOCLINETM) Metronidazole gel (ELYZOL TM) Sangvinarine gal

Tetracycline antibiotics: Tetracycline-HCl in vitro displays substantivity to dentin tooth surfaces, and maintains its antimicrobial activity upon desorption . Therapeutic levels of tetracycline-HCl persist in gingival crevicular fluid for 3-21 days following subgingival drug placement with irrigation solutions or paste formulations . Thus, sustained pocket delivery of tetracycline-HCl may be attained using the tooth root surface as a slow-release depot.

Metronidazole: A gel containing 25% metronidazole (Elyzol@,D umex,Copenhagen, Denmark) has recently been developed for local application into periodontal pockets and is commercially available in Europe. Metronidazole has been incorporated into gels, collagen,dialysis tubing, zinc oxide-eugenol pastes,ethylcellulose films and acrylic strips for sustained subgingival delivery. A 25% metronidazole-containing gel, which is generally cleared from subgingival sites within 24 hours after placement.

MINOCYCLINE: A 2% minocycline-containing ointment produced better reductions in probing depth, but not necessarily improved periodontal attachment levels, than a placebo ointment when utilized as an adjunct to mechanical debridement. Minocycline powder microencapsulated in a biodegradable polymer for controlled drug release provided no adjunctive 6-month clinical benefits compared to periodontal debridement alone.

AIM: The aim of this 6-month follow-up parallel study was to evaluate the efficacy of three commercially available local delivery systems as adjuncts to scaling and root planing in the treatment of sites with persistent periodontal lesions. MATERIALS & METHODS: Study design: Parallel-design study. Sample size:79 pts (50 F&29 M )with 4 pockets >5mm with BOP & suppuration. Patients with persistent pockets that did not respond favorably to scaling and root planing were randomized into 4 treatment groups.

SRP-20 pts SRP +25% tetracycline fibers-19 pts SRP+2% minocycline gel -21 pts SRP+25% metronidazole gel-19 pts Clinical parameters were recorded at -base line -6 weeks -3 months -6 months

INCLUSION CRITERIA: The patients recruited for this study had been attending the Periodontal Department of the Glasgow Dental Hospital for chronic periodontitis therapy. Pts with mean age of 45+-6.4 years. The participants had previously (at least 6months before the screening visit) received quadrant scaling and root planing under local anesthetic, and despite mechanical treatment and good oral hygiene,still had deep pockets with bleeding on probing. They had at least 4 non-adjacent teeth with probing depth 5 mm with bleeding on probing or suppuration.

EXCLUSION CRITERIA: Pts with systemic diseases . Pts with history of systemic antimicrobial therapy over the past 6 months. Sites with furcation involvement. CLINICAL MEASUREMENTS: At the baseline visit and at 6 weeks, 3 months, and 6 months after the last treatment, the following clinical parameters were measured by a single examiner. 1.pl index 2.the modified gingival index

3.duplicate probing depth recordings using an electronic probe with a controlled force of 20g. 4. duplicate attachment level recordings using the Florida Probe and occlusal stents. 5.the presence of suppuration was assessed using a ball burnisher. BOP was assessed,and the presence or absenceo of bleeding up to 30 sec after probing was recorded. TREATMENTS: 1.SRP alone. 2.SRP+2% minocycline gel;the gel application was repeated 2 & 4 weeks after the 1st application.

3.SRP+application of 25% tetracycline ethylene vinyl acetate fibers;after 10 days the pt was recalled & fibers were removed; 4.SRP+application of 25% metronidazole gel;the application was repeated 7 days later. STATISTICAL ANALYSIS: For each treatment group,the baseline and 6-week, 3-month, and 6-month probing depth and attachment level data were subjected to a paired t test. The changes in probing depth and attachment level were subjected to general linear model (GLM) procedures with the baseline probing depth as a continuous covariate.

The Kruskal-Wallis test was used to compare the percentage of bleeding on probing sites between the groups. Fisher s exact test was used to compare 2 treatments at a time. The plaque index and Modified Gingival Index data were analyzed by Wilcoxon s test for each treatment. The change in the indices was compared across treatment groups using the Kruskal-Wallis test. Where there were significant differences, post-hoc comparisons were performed using multiple MannWhitney-U tests, and the significance level was corrected using the Bonferroni adjustment for multiple comparisons.

All the statistical procedures were performed using one software package-Minitab,release 9.2. RESULTS: All 4 therapies resulted in significant improvements from baselinein-PD,CAL BOP,MGI scores. The improvements in clinical parameters were greater in all 3 adjunctive treatment groups than scaling and root planing alone. The mean probing depth reductions at 6 months were: -SRP+tetracycline=1.38mm -SRP+metronidazole=0.93mm -SRP+minocycline=1.10mm and -scaling alone=0.71mm.

While the frequency of sites with suppuration was markedly reduced following all antimicrobial treatments, the most effective reductions were seen in the scaling plus tetracycline fiber group, followed by the minocycline group.

DISCUSSION: This study evaluated the clinical response to 3 locally delivered antimicrobials as adjuncts to scaling and root planing. The participants in this study had already been treated for chronic periodontal disease using quadrant scaling and root planing under local anesthesia and still had pockets 5 mm with bleeding on probing or suppuration. All adjunctive antimicrobial treatments in this study produced greater mean improvements in all clinical parameters than scaling alone (although the S+Tet treatment was consistently a statistically significantly better therapy). This suggests that at sites with persistent periodontal disease, despite previous mechanical therapy,adjunctive local antimicrobial treatment is effective.

The sustained concentration of tetracycline at very high levels,greater than 1.6 mg/mL in the crevicular fluid over 10 days,25 could explain the superiority of this treatment modality over other locally delivered antimicrobials in the treatment of suppuration and chronic abscesses. Goodson has estimated that the fluid in a 5mm pocket is replaced 40 times during one hour, which represents a very high clearance rate. Any substance that is not capable of binding within the pocket will be rapidly removed, even if placed originally at a very high concentration.

Langer and Peppas32 describe 2 classes of local delivery devices, sustained and controlled delivery devices. the difference between the antimicrobial treatments did not reach statistically significant levels at the 6month time point. This lack of significant difference among the antimicrobial treatments at the end of the study could be due in part to a small relapse in the improvement at the 6-month time point regardless of the treatment performed,resulting in a dilution of the difference between groups. the so-called Hawthorne effect may be responsible in part for a better improvement in this group as compared to pre-baseline status of these sites, due to their improved home care after inclusion in the study.

CONCLUSION: Although all 3 locally applied antimicrobial systems seem to offer some benefit over scaling and root planing alone, a treatment regimen of scaling and root planing plus tetracycline fiber placement gave the greatest reduction in probing depth over the 6 months after treatment.

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