Doxycycline treatment significantly reduced the anaerobic population in plaque but did not result in a change in either the number of resistant bacteria present or the acquisition of antibiotic resistance.
The present study evaluated the clinical response of periodontal pockets in beagle dogs after treatment with a biodegradable delivery system containing 10% doxycycline hyclate (ABDS-D). Eight adult, female beagle dogs had generalized, severe periodontitis with plaque and calculus-laden pockets. In each animal, 3 teeth with multiple pocket sites > or = 4 mm (mean depth = 6.0 mm) associated with attachment loss (mean = 5.4 mm) and which bled on probing (mean score = 2.5) were treated with a single application of either ABDS-D (experimental group) or the delivery system alone without the doxycycline (control group). Residual polymer was removed at day 7. Bioassay of doxycycline in gingival crevicular fluid associated with presence of ABDS-D gave mean levels of bioactivity of approximately 250 micrograms/ml. Levels of bioactive doxycycline were detected for approximately 7 days after ABDS-D removal. Periodontal maintenance consisted of thrice-weekly toothbrushing the treated sites. Clinical responses were evaluated at 2 weeks, and at bi-weekly intervals thereafter for 4 months. Analyses of the data from the control group showed that there was only slight clinical improvement. In contrast, in the experimental group, bleeding on probing and probing depths were significantly reduced from baseline at all post-treatment time points. At 1 month, mean probing depth reduction was 2.4 mm and this was maintained at 4 months (mean reduction = 2.5 mm). These probing depth reductions occurred primarily through gain of clinical attachment which was 2.0 mm at 4 months. Bleeding had been virtually eliminated (mean = 0.2). It was concluded that, for the beagle dogs with severely infected periodontal pockets in this study, treatment with subgingival doxycycline using the delivery system resulted in substantial improvement in periodontal health.
The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells. Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time. Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections. However, their effects on host immune cells during different treatment regimens are not known. Due to their ability to serve as the first line of host defense against microbial infections, we have compared the effects of these antimicrobial agents on human neutrophil functions and viability. The results show that SANG is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested. However, exposures of neutrophils to very low concentrations of SANG (0.001%) inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min. Increasing the exposure time results in a similar inhibition of neutrophil functions, albeit at 50-100 fold lower concentrations of SANG. CHX rapidly disrupts the cell membrane of both crevicular and peripheral blood neutrophils at concentrations above 0.005% within 5 min, and inhibition of all neutrophil functions is due to its lytic properties. While TET is least toxic to neutrophils, a dose dependent inhibition of neutrophil functions is dependent on the calcium concentrations of the cellular environment, and is observed only above 0.04% or higher concentrations in the absence of calcium. The data suggest that a critical cumulative concentration of these drugs is essential for their toxicity and inhibition of neutrophil functions. Therefore, both the length of exposure and the dose of the drug both are critical while considering the effectiveness of SANG, CHX or TET in the treatment of infections. Furthermore, due to differences in their mechanisms of action, the consequences of their effects on neutrophils may have significant bearing on tissue pathology as well as on their therapeutic efficacy.
An increased incidence of antibiotic‐resistant bacteria and yeast overgrowth has been reported following various periodontal treatments. The objective of this study was to detect possible overgrowth of opportunistic bacteria and fungi as well as changes in normal microbiota after application of a biodegradable delivery system containing 5% sanguinarium (ABDS‐S) to one quadrant in a split‐mouth study. An oral hygiene quadrant served as a control. The ABDS‐S treated and control periodontal sites as well as the saliva of 17 subjects were sampled prior to treatment, immediately after ABDS‐S removal at 7 days, and again at 30 and 60 days. At Day 7 sanguinariumresistant bacteria increased in both control and ABDS‐S periodontal sites as well as in the saliva. Enteric Gram‐negative bacilli in both control and ABDS‐S periodontal sites were 2.2 to 3.4 log colony forming units higher at Day 7 compared to baseline. This overgrowth was transient in that levels became undetectable at Days 30 and 60. No such overgrowth was observed for C. albicans or other fungi, or for S. aureus or other staphylococci in any periodontal sites. Levels of Actinomyces increased at Days 30 and 60 in both control and ABDS‐S sites as well as saliva. These changes strongly suggest that a 7 day ABDS‐S treatment in one quadrant of the mouth led to significant microbiota changes in the treated and control quadrants as well as in the saliva. Future microbial studies involving antimicrobials delivered by local delivery systems must consider the crossover effects of treatment inherent in the split‐mouth design. J Periodontol 1995;66:870–877.
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