¶ … Role of Antibiotic Therapy in the Treatment of Periodontal Disease? The objective of this work is to examine the role of antibiotic therapy in the treatment of periodontal disease. Also examined will be the delivery system, the type of antibiotics and efficacy as an adjunct to mechanical therapy in the management of periodontal disease. Toward this end, this work will examine the literature in this area of study including literature located in professional and academic journal and publications.

Sub-Antimicrobial Dose Doxycycline

The work of Preshaw, et al. (2005) entitled "Long-Term Treatment with Sub-Antimicrobial Dose Doxycycline Has No Antibacterial Effect on Intestinal Flora" reports a study that sought to determine if a nine-month regimen of subantimicrobial doxycycline (20 mg. bid) had an effect on either the intestinal or the vaginal microflora. The study involved 69 individuals with periodontal disease who were randomized to receive drug or placebo control for a nine-month period. It is reported that stool specimens and vaginal swabs were collected at baseline and after three and nine months of therapy. Samples were examined for total anaerobic counts, opportunistic pathogens, and doxycycline-resistant bacteria. It is reported that "{all isolates that survived sub-culture were identified and their susceptibilities determined to six antibiotics." Preshaw et al. states "Substantial evidence indicates that the adjunctive use of sub-antimicrobial dose doxycycline (SDD) consisting of 20mg doxycycline hyclate (Periostatt, CollaGenex Pharmaceuticals Inc., Newtown, PA, USA), bid, provides a significant benefit to scaling and root planning (SRP) in the treatment of periodontitis because of the anticollagenase and anti-inflammatory activities of doxycycline. However, serious concern has been expressed that even sub-antimicrobial levels of doxycycline may exert a detrimental antimicrobial effect on the normal flora." (Preshaw, et al., 2005) It is reported that this effect might result in "…the disruption or suppression of the normal flora and lead to its colonization or overgrowth by opportunistic pathogens as well as the development of non-susceptible microorganisms." (Preshaw, et al., 2005) The study reported by Preshaw et al. states findings as follows: "Therefore, we concluded that the level of doxycycline present in the intestines was too low to promote or stimulate resistance. The trend detected in the number of doxycycline-resistant bacteria at 3 months is believed to be because of the initial imbalance present prior to drug administration and possibly to microbial variation because of dietary changes or to microbial sampling. As no differences between treatment groups were detected at 3 months in the predominant taxa recovered or in the MICs obtained, it was concluded that the trend observed at 3 months was not drug related." (Preshaw, et al., 2005)

II. Utilization of Locally Delivered Doxycycline in Non-Surgical Periodontitis Treatment

The work of Wennstrom (2001) entitled "Utilization of Locally Delivered Doxycycline in Non-Surgical Treatment of Chronic Periodontitis" reports a six-month multicenter trial in which two different approaches to non-surgical treatment of chronic periodontitis were examined through use of delivery of controlled -- release doxycycline for evaluation. The study involved 105 adult patients with moderately advanced chronic periodontitis form three participating centers in the trial. The study report states that each patient was required to "… present with at least 8 periodontal sites in 2 jaw quadrants with a probing pocket depth (PPD) of >5 mm and bleeding following pocket probing (BoP), out of which at least 2 sites had to be >7 mm and a further 2 sites >6 mm. Following a baseline examination, including assessments of plaque, PPD, clinical attachment level (CAL) and BoP, careful instruction in oral hygiene was given." (Wennstrom, 2001) Patients were assigned randomly to one of two treatment groups stated to be those of: (1) scaling/root planing (SRP) with local analgesia; or (2) debridement (supra- and subgingival ultrasonic instrumentation without analgesia)." (Wennstrom, 2001) It is reported that the "SRP" group "…received a single episode of full-mouth supra-/subgingival scaling and root planing under local analgesia. In addition, at a 3-month recall visit, a full-mouth supra-/subgingival debridement using ultrasonic instrumentation was provided. This was followed by subgingival application of an 8.5% w/w doxycycline polymer at sites with a remaining PPD of >5 mm." (Wennstrom, 2001) The study also reports that the debridement patient group was "initially subjected to a 45-minute full-mouth debridement with the use of an ultrasonic instrument and without administration of local analgesia, and followed by application of doxycycline in sites...

At month 3, sites with a remaining PPD of >5 mm were subjected to scaling and root planing. Clinical re-examinations were performed at 3 and 6 months." (Wennstrom, 2001) Findings in the study report that at three months "…the proportion of sites showing PPD of 2 mm) was higher in the "debridement" group than in the "SRP" group (38% versus 30%; p,0.05). At the 6-month examination, no statistically significant differences in PPD or CAL were found between the two treatment groups. BoP was significantly lower for the "debridement" group than for the "SRP" group (p,0.001) both at 3- and 6 months. The mean total treatment time (baseline and 3-month) for the "SRP" patients was 3:11 h, compared to 2:00 h for the patients in the "debridement" group (p,0.001)." (Wennstrom, 2001) The study concludes that it is indicated by the results that serve to simplify "...subgingival instrumentation combined with local application of doxycycline in deep periodontal sites can be doxycycline; local drug delivery; multicenter; periodontitis; scaling and root planning considered as a justified approach for non-surgical treatment of chronic periodontitis." (Wennstrom, 2001)
III. Systematic Review on Effect of Systemic Antimicrobials as Adjunct to Scaling and Root Planning

The work of Herrera, et al. (2002) entitled "systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients" reports a study in the form of a systematic review for the purpose of evaluation of the effectiveness of the adjunctive use of systemic antimicrobials with scaling and root planning (SRP) vs. SRP alone in the treatment of chronic (CP) or aggressive periodontitis (AgP)." The study used computerized databases including MEDLINE and EMBASE and selected journals by hand until April 2001. Criteria for selection of study included those that were designed as controlled clinical trials "in which systematically healthy patients with either AgP or CP were treated with SRP plug systemic antimicrobials on comparison with SRP alone or with placebo, for a minimum of 6 months." (Herrera, et al., 2002) It is reported that the primary outcome measures "…were clinical attachment level (CAL) change and probing pocket depth (PPD) change." (Herrara, et al., 2002) Herrera et al. states that data collection and analysis involved two reviewers who "...extracted independently information regarding quality and study characteristics, in duplicate. Kappa scores determined their agreement. Main results were collected and grouped by drug, disease, and PPD category. For the quantitative data synthesis, the data was pooled (when mean differences and standard errors were available), and either a Fixed Effects or Random Effects meta-analysis was used for the analysis." (Herrera, et al., 2002) The study reports that following the first selection that 158 papers were identified through both manual and electronic searches and 25 deemed eligible to be included in the study. The study reports that the assessment of quality indicated "…randomization and allocation concealment methods were seldom reported and blindness was usually not defined clearly. In general, selected studies showed high variability and lack of relevant information for an adequate assessment. Overall, SRP plus systemic antimicrobial groups demonstrated better results in CAL and PPD change than SRP alone or with placebo groups. Only limited meta-analyses could be performed, due to the difficulties in pooling the studies and the lack of appropriate data. This analysis showed a statistically significant additional benefit for spiramycin (PPD change) and amoxicillin/metronidazole (CAL change) in deep pockets.' (Herrera, et al., 2002) The study concluded that systematic antimicrobials in conjunction with SRP can offer an additional benefit over SRP alone in the treatment of periodontitis and specifically offer a benefit over SRP alone in treating periodontitis.

IV. Effects of Metronidazole Plus Amoxicillin

The work of Lopez, et al. (2006) entitled "Effects of metronidazole plus amoxicillin as the only therapy on the microbiological and clinical parameters of untreated chronic periodontitis" reports a study with the objective of determining the "effect of metronidazole plus amoxicillin (M1A) as the sole therapy, on the subgingival microbiota of chronic periodontitis." (Lopez, et al., 2006) The study reports that 22 patients "…with untreated chronic periodontitis were randomly assigned to a group that received M1A for 7 days, or to a group receiving scaling and root planing (SRP) and two placebos." (Lopez, et al., 2006) Clinical measures included "…sites with plaque, bleeding on probing (BOP), probing depth (PD) and attachment level (AL)" and these were reported to have been "made at baseline, 3, 6, 9 and 12 months. " (Lopez,…