Systemic doxycycline administration in the treatment of periodontal infections (I). Effect on the subgingival microbiota.

Systemic doxycycline is one of the more common antimicrobial agents used in the treatment of periodontal infections and yet little is known of its effect on subgingival plaque composition during and after its administration. The purpose of the present investigation was to evaluate changes in subgingival plaque composition during and after 14 days of doxycycline administration. 20 subjects with adult periodontitis were randomly assigned to test (n = 10) and control (n = 10) groups. The subjects received full mouth clinical assessment of pocket depth, attachment level, BOP, gingival redness, suppuration and plaque accumulation at baseline and 90 days. All subjects received full mouth SRP at baseline and, additionally, the test group received 100 mg doxycycline daily for 14 days. Subgingival plaque samples were taken from the mesial surface of up to 28 teeth in each subject at baseline and 90 days. In addition, plaque samples were taken from 2 randomly selected teeth at 3, 7 and 14 days during and after antibiotic administration. Control subjects were sampled at the same time points. Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization and fluorescent detection. Significance of differences between test and control groups was determined at each time point using the Mann Whitney test. Significance of changes over time within test and control groups was determined using the Quade test. A modest but significant reduction in mean pocket depth from baseline to 90 days occurred in both test and control groups. A significant decrease in the % of sites with gingival redness occurred in the test group. There were no significant differences in proportions between test and control groups for 33 of the test species at any time point. Test subjects exhibited lower proportions of 4 Actinomyces species and an increase in 3 Streptococcus species during antibiotic administration. After cessation of doxycycline, Actinomyces sp. increased while Streptococcus sp. returned to baseline proportions. The relationship between these 2 genera appeared to be reciprocal; an increase in one was accompanied by a decrease in the other. Periodontal pathogens including B. forsythus, P. gingivalis, T. denticola and A. actinomycetemcomitans were not significantly altered by oral administration of doxycycline using conventional therapeutic dosage.

Systemic doxycycline administration in the treatment of periodontal infections (II). Effect on antibiotic resistance of subgingival species.

The purpose of this investigation was to determine the proportion and prevalence of doxycycline resistant species in subgingival plaque samples taken during and after doxycycline administration. 20 subjects with adult periodontitis were randomly assigned to test (n = 10) or control groups (n = 10). Saliva samples as well as subgingival plaque samples taken from the distal surface of 6 posterior teeth were collected at baseline. All subjects received full mouth SRP and the test group systemic doxycycline at the dosage of 100 mg/day for 14 days. Saliva samples and plaque samples from the distal surface of 2 randomly selected teeth were taken at 3, 7 and 14 days during and after antibiotic administration. Control subjects were sampled at the same time points. Samples were anaerobically dispersed and serially diluted in PRAS Ringer's solution and plated on enriched Trypticase soy blood agar plates with or without 4 microg/ml doxycycline. After 7 days of anaerobic incubation, colonies were counted on both sets of plates. Microbial growth was washed from the doxycycline-containing media and the species identified using 40 DNA probes and checkerboard DNA-DNA hybridization. Differences in proportions of resistant species between test and control groups were tested for significance at each time point using the Mann Whitney test and over time within each group using the Quade test. The mean % (+/-SEM) of isolates resistant to 4 microg/ml doxycycline in the plaque samples of the test subjects increased from 6+/-2 to 48+/-9% during doxycycline administration, decreasing to 25+/-6% 2 weeks later and 9+/-2% at 90 days. In saliva, the % of resistant isolates rose from 13+/-1% to 81+/-10% during doxycycline administration falling to 46+/-8% 2 weeks later and 22+/-5% at 90 days. The % of resistant isolates did not change significantly in plaque or saliva samples of the control subjects at the same time points. For all subject visits combined, the most prevalent resistant species were: Streptococcus anginosus, Streptococcus oralis, Streptococcus intermedius, Streptococcus sanguis, Streptococcus mitis, Veillonella parvula, Actinomyces gerencseriae, Streptococcus constellatus, Actinomyces naeslundii genospecies 2, Streptococcus gordonii, Eikenella corrodens and Actinomyces naeslundii genospecies 1. Doxycycline resistant strains of these species were detected in both plaque and saliva samples prior to therapy and in the control group. Despite the finding of increased resistance, approximately 50% of the organisms present at periodontal sites at the end of 14 days of doxycycline administration tested sensitive to the agent.