Randomized controlled trial of doxycycline in prevention of recurrent periodontitis in high-risk patients: antimicrobial activity and collagenase inhibition

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Abstract

82 patients with a recent history of periodontal abscesses and/or loss of gingival attachment (GAL) despite active periodontal therapy were enrolled in a double-blind, randomized, placebo-controlled trial. Clinical measurements and subgingival scaling were performed every 2 months. If any site exhibited greater than or equal to 2 mm loss of GAL or a periodontal abscess, patients were administered either 100 mg Doxycycline per day for 3 weeks or placebo. During 12 months of monitoring, 55 patients exhibited recurrent active disease and were then randomly assigned to either the Doxycycline or placebo groups. Clinical measurements of GAL and microbiological culture of subgingival bacteria were made at intervals between 1 week and 7 months after completion of the drug regime. Within 7 months, 15 out of 19 patients on placebo exhibited recurrent disease compared to 13 out of 29 patients on Doxycycline, a relative risk reduction of 43% (p less than 0.05) for Doxycycline compared to placebo. Minimal inhibitory concentrations of Doxycycline for subgingival plaque samples from active sites ranged between 25-100 micrograms/ml, which are several fold higher than reported crevicular fluid concentrations for this drug. However gingival crevicular fluid collagenase was inhibited in vitro at concentrations of 5-10 micrograms/ml Doxycycline. These data indicate that Doxycycline provides significant risk reduction of recurrent periodontitis in patients with active disease.

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A long-term survey of tooth loss in 600 treated periodontal patients.

Paula B. Wasserman, L HIRSCHFELD (1978)

1. Six hundred patients in a private periodontal practice were reexamined an average of 22 years after their active treatment and the patterns of tooth loss were observed. 2. During the post-treatment period, 300 patients had lost no teeth from periodontal disease, 199 had lost one to three teeth, 76 had lost 4 to 9 teeth and 25 had lost 10 to 23 teeth. 3. Of 2,139 teeth that originally had been considered of questionable prognosis, 666 were lost. Of these, 394 were lost by one sixth of the patients and only 272 by the other five-sixths. 4. Of 1,464 teeth which originally had furcation involvements, 460 were lost, 240 of them by one-sixth of the patients who deteriorated most. 5. The mortality of teeth which were treated with periodontal surgery was compared with that of teeth which did not have surgery. Tooth retention seemed more closely related to the case type than the surgery performed. 6. In general, periodontal disease is bilaterally symmetrical and there is a predictable order of likelihood of tooth loss according to position in the arch.

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Tooth loss in 100 treated patients with periodontal disease. A long-term study.

W T McFall (1982)

A population of 100 patients with periodontal disease who had been treated and maintained for 15 years or longer was studied for tooth loss. The patients averaged 43.8 years of age and consisted of 59 females and 41 males. Patients were examined and their dental records were reviewed. On the basis of response to therapy and tooth loss, the patients were classified as Well-Maintained (77), Downhill (15), or Extreme Downhill (8). At the completion of initial treatment, 2,627 teeth were present. Of this number, during the maintenance period, 259 teeth (9.8%) were lost due to periodontal disease, while 40 teeth (1.5%) were lost due to other causes. Evaluation was made as to patterns of tooth loss, loss of questionable teeth, loss of teeth with furcations, surgical vs. nonsurgical therapy, and presence of fixed or removable prostheses. Considerable variation occurred between response groups. Periodontal disease appears to be bilaterally symmetrical and tooth loss response emulated this pattern with greatest loss of maxillary second molars and least loss of mandibular cuspids.

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Periodontal therapy in humans. I. Microbiological and clinical effects of a single course of periodontal scaling and root planing, and of adjunctive tetracycline therapy.

P MASHIMO, Steven LeVine, Robert J. Genco … (1979)

The present results showed that maarked and long-lasting changes in the subgingival microflora associated with periodontal disease could be achieved by a single course of periodontal treatment. Immediately following therapy, the total number of subgingival organisms decreased 10- to 100-fold and the proportions of cultivable Gram negative organisms and anaerobic organisms generally decreased 3- to 4-fold or more. After treatment, most periodontal pockets were populated by a scant microflora predominated by facultative Actinomyces and Streptococcus species. The kinetics of the subgingival bacterial recolonization revealed that the total cell counts and the proportions of spirochetes and Capnocytophaga species did not reach their pretreatment levels even after 6 months. Other Gram negative anaerobic species returned to pretreatment proportions after 3 to 6 months. Several Gram positive species exhibited higher posttreatment than pretreatment proportions throughout the 6 months study. The microbiological shifts paralleled significant changes in the clinical status of the periodontal tissues. Following therapy, the periodontal pocket depths decreased generally 1 to 4 mm, the gingival inflammatory index, the gingival fluid flow, and the suppurative index were generally lower, and nine of 33 test pockets examined showed apposition of alveolar bone. The microbiological and clinical changes described were exhibited by two patients treated with periodontal scaling and root planing alone and by two patients treated with the adjunctive use of systemic tetracycline therapy. In two other patients, mechanical periodontal therapy only slightly reduced the total number of subgingival organisms and the proportions of spirochetes and other Gram negative anaerobic rods. A shift in the subgingival microbial composition was achieved in these two patients after tetracycline therapy. The following model for treatment of periodontal disease is proposed: (1) Conventional therapy including thorough periodontal scaling and root planing; (2) Monitoring the subgingival flora and the clinical course; and (3) Use of antimicrobial therapy in refractory cases. Further studies are needed to develop means for rapid identification of refractory patients, and to determine the optimal antimicrobial agent, the optimal route of administration, and the optimal dosage regime.