Mark H Bradshaw

Newcastle University, Newcastle upon Tyne, ENG, United Kingdom

Are you Mark H Bradshaw?

Claim your profile

Publications (17)47.63 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies showed that adjunctive subantimicrobial dose doxycycline (SDD; 20 mg, twice daily) provides significant clinical benefits to scaling and root planing (SRP). A modified-release SDD formulation containing 40 mg doxycycline (SDD-40) to be taken once daily has been developed. The aim of this study was to investigate the efficacy of SDD-40 when used as an adjunct to SRP for the treatment of periodontitis. A 9-month, double-masked, randomized, placebo-controlled, multicenter study was conducted to test the efficacy of adjunctive SDD-40 in 266 subjects with periodontitis. Subjects were treated by SRP and randomized to receive SDD-40 or placebo for 9 months with evaluations at 3, 6, and 9 months. Adjunctive SDD-40 provided significantly greater clinical benefits than placebo at all time points. At month 9, at sites with baseline probing depths (PD) > or =6 mm, 72% to 76% of sites in the SDD-40 group demonstrated clinically significant PD reductions and clinical attachment level (CAL) gains > or =2 mm compared to 56% to 58% of sites in the placebo group (P <0.0001); 48% to 52% of sites in the SDD-40 group demonstrated PD reductions and CAL gains > or =3 mm compared to 32% of sites in the placebo group (P <0.0001). In moderate sites (baseline PD 4 to 6 mm), adjunctive SDD-40 provided significant clinical benefits compared to placebo for mean CAL (all time points: P <0.05), PD (3 months: P = 0.002; 6 and 9 months: P = 0.001), and bleeding on probing (BOP) (3 months: P <0.01; 6 months: P <0.02; 9 months: P <0.05). In deep sites (baseline PD > or =7 mm), SDD-40 provided significant benefits over control for mean CAL (3 months: P <0.05; 6 and 9 months: P <0.01), PD (all time points: P <0.001), and BOP (3 months: P <0.05; 6 months: not statistically significant; 9 months: P <0.05). Compliance with study medication was high (>92%) with no significant differences in adverse events between groups and no evidence of microbiologically significant changes or development of antibiotic resistance in the subgingival flora in either group. SDD-40 used as an adjunct to SRP resulted in significantly greater clinical benefits than SRP alone in the treatment of periodontitis.
    Journal of Periodontology 04/2008; 79(3):440-52. · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies showed that host modulation therapy (HMT) or topical antimicrobial therapy (TAT) provided significant adjunctive benefits to scaling and root planing (SRP) in the treatment of chronic periodontitis (CP). The purpose of this study was to evaluate a combination therapy involving SRP, HMT, and TAT in the treatment of moderate to severe CP. A 6-month, randomized, multicenter, placebo-controlled, examiner-masked study was undertaken to evaluate the clinical usefulness of a combination treatment of systemically delivered doxycycline hyclate (HMT; 20 mg, twice a day) plus locally delivered doxycycline hyclate gel (TAT; 10%, in pockets > or =5 mm) in combination with SRP versus SRP plus placebo. Clinical outcomes included mean changes in probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and gingival index (GI) at baseline and at 3 and 6 months. In 171 subjects, combination therapy provided significantly greater clinical benefits than control therapy for all clinical measures at 3 and 6 months. In moderate CP (PD of 4 to 6 mm), combination therapy provided significant benefits over control for PD (3 and 6 months: P <0.01), CAL (3 months: P <0.01; 6 months: P <0.03), BOP (3 months: P <0.02; 6 months: P <0.05), and GI (3 months: P <0.01; 6 months: P <0.03). In severe CP (PD > or =7 mm), combination therapy provided significant benefits over control for PD (3 and 6 months: P <0.01), CAL (3 months: P <0.01; 6 months: P <0.02), BOP (3 months: P <0.01; 6 months: P >0.05), and GI (3 months: P <0.01; 6 months: P <0.01). Combination therapy, including SRP, HMT, and TAT, provided significantly greater clinical benefits than SRP alone in the treatment of moderate to severe CP.
    Journal of Periodontology 01/2008; 79(1):33-41. · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Doxycycline monotherapy at antimicrobial doses has been shown to be effective for the treatment of rosacea. To evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea. In two phase III, parallel-group, multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count. The mean lesion count at baseline was approximately 20 in each study arm. At week 16, the mean change from baseline in lesion count in the active-treatment groups was -11.8 in study 301 and -9.5 in study 302 compared with -5.9 and -4.3, respectively, in the placebo groups (P < .001 for both comparisons). Anti-inflammatory dose doxycycline was well tolerated; the most common adverse events were nasopharyngitis (4.8%), diarrhea (4.4%), and headache (4.4%). In both studies, the reduction of inflammatory lesion counts did not plateau within the 16-week time frame in either treatment group. Rosacea is often treated for a period of months or years. The duration of the studies did not allow for assessment of safety beyond 16 weeks or whether the progressive improvement seen with active treatment would continue beyond 16 weeks. Neither study assessed the effect of treatment in patients with only erythematotelangiectatic (subtype 1) rosacea. Once-daily anti-inflammatory dose doxycycline appears to be effective and safe for the treatment of rosacea.
    Journal of the American Academy of Dermatology 06/2007; 56(5):791-802. · 4.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recurrent oral aphthous ulceration (ROAU) is a common problem that can result in considerable pain and distress for patients. The aim of this pilot study was to evaluate the role of subantimicrobial dose doxycycline (SDD - 20 mg doxycycline twice daily) in the management of patients with ROAU. 50 patients with ROAU were randomly allocated to treatment with SDD or placebo for 90 days. Daily ulcer diaries were completed by the participants to record the number of new ulcers and the pain associated with the ulcers. There were significantly more days with no new ulcers in the SDD group (80.4 +/- 5.9) than the placebo group (69.8 +/- 18.7; P=0.04). Strong trends were observed towards fewer new ulcers per day, fewer new ulcers over the 90-day period, and more days with no pain in the SDD group compared with the placebo group (P=0.06-0.08). SDD shows promise as potential therapy in the management of ROAU, though this needs to be confirmed in further studies.
    Journal of Oral Pathology and Medicine 04/2007; 36(4):236-40. · 2.06 Impact Factor
  • Klaus Theobald, Mark Bradshaw, James Leyden
    [Show abstract] [Hide abstract]
    ABSTRACT: Two large clinical trials have recently demonstrated the efficacy of a 40-mg controlled-release formulation of doxycycline in the treatment of rosacea, a dose well below the conventional level of 100 to 200 mg/d. Since no formal dose-response studies have been conducted, the authors analyzed phase 3 data to determine whether a dose-efficacy relationship exists. Standard parametric regression analyses were used to estimate the correlations between dose (mg/kg body weight) and overall drug exposure (area under the curve [AUC]) in a phase 1 pharmacokinetic study and between dose and efficacy (mean change from baseline in total inflammatory lesion count at week 16) in 2 pooled phase 3 clinical efficacy studies. Additional regressions were run at each visit for the clinical efficacy studies to determine whether results differed across visits. A regression analysis was also performed in a subset of patients who showed a greater efficacy response. We found overall drug exposure (AUC) to have a highly significant correlation with dose (mg/kg) (r=0.49; P=.006). In contrast, clinical efficacy did not correlate with dose at any of the visits at week 3 (r=0.01; P=.85), week 6 (r=0.04; P=.53), week 12 (r<0.01; P=.98), and week 16 (r=0.03; P=.64) or among the subset of patients who showed greater clinical benefit. Higher mg/kg doses led to higher plasma concentrations but did not lead to increased clinical efficacy. Anti-inflammatory dose doxycycline (40-mg controlled-release formulation) conferred peak anti-inflammatory efficacy in the treatment of rosacea.
    SKINmed 01/2007; 6(5):221-6.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Subantimicrobial doses of doxycycline may improve outcomes in rosacea when combined with topical metronidazole and used as maintenance monotherapy. The purpose of this study was to evaluate the safety and efficacy of doxycycline hyclate 20 mg (subantimicrobial dose doxycycline) administered twice daily as an adjunct to metronidazole 0.75% topical lotion in the treatment of rosacea. Patients received subantimicrobial doses of doxycycline twice daily plus metronidazole (n = 20) or placebo plus metronidazole (n = 20) for 12 weeks. Subantimicrobial-dose doxycycline or placebo monotherapy continued for 4 weeks. The primary efficacy measure was change from baseline in total inflammatory lesions at weeks 2 and 16. Total inflammatory lesions were reduced significantly (P =.048) by week 4 and by all subsequent visits in the subantimicrobial-dose doxycycline/metronidazole group compared with placebo/metronidazole. Changes from baseline increased over time and were maintained during subantimicrobial-dose doxycycline monotherapy. Adjunctive use of subantimicrobial dose doxycycline significantly reduced the clinical signs of rosacea compared with metronidazole alone and may be useful maintenance monotherapy.
    Journal of the American Academy of Dermatology 12/2005; 53(5):791-7. · 4.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to determine if a 9-month regimen of sub-antimicrobial doxycycline (20 mg, bid) had an effect on either the intestinal or the vaginal microflora. A total of 69 periodontally diseased subjects were randomized to receive drug or placebo control for a 9-month period. Stool specimens and vaginal swabs were collected at baseline and after 3 and 9 months of therapy. Samples were examined for total anaerobic counts, opportunistic pathogens, and doxycycline-resistant (>or=4 microg/ml) bacteria. All isolates that survived sub-culture were identified and their susceptibilities determined to six antibiotics. Analyses were performed to determine if treatment differences were present. The only statistically significant differences (p<0.05) between the two treatment groups occurred in the doxycycline-resistant counts at the baseline sample period for the faecal samples. This imbalance was before treatment initiation and the administration of the study drug. No between-treatment differences were detected at either the 3- or 9-month sample period either in the predominant bacterial taxa present or in their antibiotic susceptibilities. There was no evidence that sub-antimicrobial doxycycline treatment exerted an effect on the composition or doxycycline resistance level of either the faecal or the vaginal microflora.
    Journal Of Clinical Periodontology 11/2005; 32(11):1163-9. · 3.69 Impact Factor
  • Philip M Preshaw, Arthur F Hefti, Mark H Bradshaw
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have demonstrated the clinical benefits of sub-antimicrobial dose doxycycline (SDD) in the treatment of chronic periodontitis (CP). The aim of this study was to retrospectively evaluate the role of SDD as an adjunct to scaling and root planing (SRP) in the treatment of smokers and non-smokers with CP. A meta-analysis of two previously reported clinical studies was undertaken. Both were 9-month, double-blind, randomized, placebo-controlled, multi-centre clinical trials that investigated the efficacy of SDD (20 mg doxycycline twice daily) in combination with SRP in subjects with moderate-severe CP. 36.9% of the combined study population were smokers. Three hundred and ninety-two subjects were included in the meta-analysis, which evaluated per-subject mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline and the total number of sites with attachment gains and PD reductions > or =2 and > or =3 mm from baseline in four subgroups: smokers/SDD; smokers/placebo; non-smokers/SDD; non-smokers/placebo. A hierarchical treatment response was observed, with non-smokers who received SDD demonstrating the greatest CAL gains and PD reductions. Smokers who received placebo demonstrated the smallest clinical improvements following treatment. Smokers who received SDD demonstrated an intermediate treatment response that was broadly equivalent to that seen in non-smokers who received placebo. In sites with baseline PD 4-6 mm, month 9 CAL gains were 19-45% better in non-smokers who received SDD compared with all other subgroups (p<0.05), and were 21% greater in smokers who received SDD compared with smokers who received placebo (p<0.05). Furthermore, month 9 PD reductions were 21-53% greater in non-smokers who received SDD compared with all other subgroups (p<0.01), and were 26% greater in smokers who received SDD compared with smokers who received placebo (p<0.05). Adjunctive SDD enhances therapeutic outcomes compared with SRP alone, resulting in clinical benefit in both smokers and non-smokers with CP.
    Journal Of Clinical Periodontology 07/2005; 32(6):610-6. · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the efficacy of subantimicrobial dose doxycycline (SDD; 20 mg doxycycline twice daily) as an adjunct to scaling and root planing (SRP) in the treatment of moderate-severe chronic periodontitis (CP) in institutionalised elderly patients aged 65 years or older. Previous studies have shown that SDD is of clinical benefit in the treatment of CP. However, the benefits of SDD in geriatric populations (65+ years) have not been determined. A 9-month, double-blind, randomised, placebo-controlled pilot study was conducted. 24 institutionalised geriatric patients (65 years or older) with evidence of CP manifested by baseline clinical attachment levels (CAL) 5-9 mm, probing depths (PD) 4-9 mm and bleeding on probing (BOP) were recruited. At baseline, patients were treated by a standardised episode of SRP, and randomised to receive either adjunctive SDD or placebo. Full mouth PD and CAL were measured using the manual UNC-15 periodontal probe at 3, 6, and 9 months post-baseline to assess the response to treatment. Periodontal sites were stratified by baseline PD value: sites with PD 4-5 mm were considered moderately diseased and sites with PD > or = 6 mm severely diseased. The SRP + placebo resulted in PD reductions similar to those reported previously in the literature. At all time-points and in both moderate and deep sites, SRP + SDD resulted in significantly greater PD reductions relative to baseline than SRP + placebo. At month 9, in moderate sites, mean PD reductions of 1.57 +/- 0.11 mm were reported in the adjunctive SDD group, compared with 0.63 +/- 0.11 mm in the adjunctive placebo group (p < 0.001). In deep sites at month 9, mean PD reductions of 3.22 +/- 0.29 mm were reported in the adjunctive SDD group, compared with 0.98 +/- 0.31 mm in the adjunctive placebo group (p < 0.05). Similar improvements were observed for CAL in the SDD group compared with the placebo group. Significantly lower BOP scores were also recorded at month 9 in the SDD group (7.5%) compared with the placebo group (71.2%) (p < 0.01). SDD used as an adjunct to SRP provides significant benefit for elderly patients with CP compared with SRP alone.
    Gerodontology 04/2005; 22(1):37-43. · 1.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Subantimicrobial dose doxycycline (SDD--20 mg doxycycline twice daily) is indicated as an adjunctive treatment for periodontitis. Doxycycline downregulates the activity of matrix metalloproteinases (MMPs), key destructive enzymes in periodontal disease. Current understanding of periodontal pathogenesis suggests that MMPs play a major role in the destruction of periodontal tissues, leading to the clinical signs of periodontitis. Research supports that downregulation of MMPs by SDD confers benefit to patients with periodontitis. We review the clinical, microbiological and safety data relating to the use of SDD in patients with periodontitis, and consider the historical events that led to the development of adjunctive SDD as a treatment for periodontitis. Studies have shown that SDD, when prescribed as an adjunct to scaling and root planing (SRP), results in statistically and clinically significant gains in clinical attachment levels and reductions in probing depths over and above those that are achieved by SRP alone. SRP must be thorough and performed to the highest standard to maximise the benefits of adjunctive SDD. SDD does not result in antibacterial effects, or lead to the development of resistant strains or the acquisition of multiantibiotic resistance. The frequency of adverse events is low, and does not differ significantly from placebo. Adjunctive SDD confers clinical benefit to patients with periodontitis. A comprehensive treatment strategy is suggested, involving patient education and motivation, reduction of the bacterial burden by SRP, host response modulation with SDD, and periodontal risk factor modification.
    Journal Of Clinical Periodontology 10/2004; 31(9):697-707. · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies have shown that subantimicrobial dose doxycycline (SDD) is of clinical benefit in the treatment of chronic periodontitis (CP). The aim of this study was to further assess the role of SDD as an adjunct to scaling and root planing (SRP) in the treatment of CP. A double-blind, randomized, placebo-controlled, multicenter clinical study was conducted to test the efficacy of SDD (20 mg doxycycline B.I.D.) in combination with SRP in subjects with moderate to severe CP. Two-hundred ten subjects were treated with a standardized episode of SRP and randomized to receive either adjunctive SDD or placebo for 9 months. Efficacy parameters included per-subject mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline, and the total number of sites with attachment gains and probing depth reductions > or = 2 mm and > or = 3 mm from baseline. In periodontal sites with PD 4 to 6 mm and > or = 7 mm (N = 209, intent-to-treat population), mean improvements in CAL and PD were greater following SRP with adjunctive SDD than SRP with placebo, achieving statistical significance in all baseline disease categories at month 9 (P < 0.05). At month 9, 42.3% of sites in the SDD group demonstrated CAL gain > or = 2 mm compared to 32.0% of sites in the placebo group (P < 0.01). CAL gain > or = 3 mm was seen in 15.4% of sites in the SDD group compared to 10.6% of sites in the placebo group (P < 0.05). When considering the same thresholds of change in PD, 42.9% of sites in the SDD group compared to 31.1% of sites in the placebo group demonstrated PD reduction > or = 2 mm (P < 0.01), and 15.4% of sites in the SDD group compared to 9.1% of sites in the placebo group demonstrated PD reduction > or = 3 mm (P < 0.01). Adjunctive subantimicrobial dose doxycycline enhances scaling and root planing. It results in statistically significant attachment gains and probing depth reductions over and above those achieved by scaling and root planing with placebo.
    Journal of Periodontology 08/2004; 75(8):1068-76. · 2.40 Impact Factor
  • Journal of The American Academy of Dermatology - J AMER ACAD DERMATOL. 01/2004; 50(3).
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine if treatment with subantimicrobial-dose (SD) doxycycline hyclate (20-mg tablets taken twice daily) improved clinical outcome, had any detectable effect on skin flora, led to overgrowth or colonization of skin by opportunistic pathogens, or resulted in an increase in antibiotic resistance by the surface skin microflora in patients with moderate acne compared with placebo. Multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Two university-based clinics. Adults (N = 51) with moderate facial acne. Patients were randomized to receive SD doxycycline (Periostat; CollaGenex Pharmaceuticals Inc, Newtown, Pa) or placebo twice daily for 6 months. MAIN EFFICACY OUTCOMES: Primary: changes from baseline in numbers of inflammatory, noninflammatory, and total lesions. Secondary: changes from baseline of individual counts of papules, pustules, and nodules and global assessments of clinical improvement by patient and physician. Forty patients completed 6 months of treatment. At 6 months, the SD doxycycline group had a significantly greater percent reduction in the number of comedones (P<.01), inflammatory and noninflammatory lesions combined (P<.01), and total inflammatory lesions (P<.05) than did the placebo group. They also had significantly greater improvement according to the clinician's global assessment (P =.03). There were no significant differences in microbial counts between groups and no evidence of change in antibiotic susceptibility or colonization by potential pathogens. The treatment was well tolerated. Twice-daily SD doxycycline treatment significantly reduced the number of inflammatory and noninflammatory lesions in patients with moderate facial acne, was well tolerated, had no detectable antimicrobial effect on the skin flora, and did not result in any increase in the number or severity of resistant organisms.
    Archives of Dermatology 04/2003; 139(4):459-64. · 4.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Severe, generalized periodontitis is a form of chronic periodontitis that appears to be associated with an exaggerated host response. Little information is available on the benefits of using adjunctive host modulation in the management of this form of periodontal disease. Thirty subjects < or = 45 years of age with severe, generalized periodontitis received subgingival debridement and oral hygiene instructions each week for 4 weeks, plus 6 months of adjunctive subantimicrobial doxycycline (SDD) or placebo. Periodontal status was monitored at baseline, and at 1, 3, 5.25, and 8.25 months following completion of the hygiene sessions. Maintenance therapy was performed at 3, 5.25, and 8.25 months for both groups. Ten subjects in each group completed all phases of the study. Subgingival debridement plus adjunctive SDD reduced deep pockets (> or =7 mm at baseline) by an average of 3.02 mm after 9 months versus 1.42 mm for the placebo group. A significant clinical response was seen in both groups as soon as 1 month, but the response was always clinically and statistically greater in the SDD group. In the SDD group, nearly 40% of 237 pockets > or =7 mm were reduced by > or =4 mm, and 55% were reduced by > or =3 mm. In addition, only 2 pockets deepened by > or =4 mm in the SDD group versus 10 in the placebo group. The supplementation of hygienist-delivered full mouth subgingival and supragingival debridement with a host-modulating agent, SDD, provides clinically and statistically significant benefits in the reduction of deep pockets in patients with severe, generalized periodontitis. In addition, adjunctive SDD is more effective than a placebo in preventing further increases in probing depth.
    Journal of Periodontology 07/2002; 73(7):762-9. · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Subantimicrobial dose doxycycline (SDD 20 mg bid) plus scaling and root planing (SRP) significantly improved clinical attachment level (CAL) and reduced probing depth (PD) compared with placebo plus SRP in a double-blind, placebo-controlled, multicenter study of patients with adult periodontitis (AP). In a study conducted as a follow-up, the post-treatment effects of SDD were assessed in patients who completed the SRP study. The SRP study was a 9-month, active-treatment study and the follow-up was a 3-month, no-treatment study. In the SRP study, tooth sites in qualifying quadrants were scaled and root planed and patients were randomized to receive twice daily SDD 20 mg or placebo. In the follow-up, patients received no study drug; investigators and patients remained blinded to the previous treatment group assignments. Efficacy measures included the change in CAL and PD from baseline values determined at the start of the SRP study in tooth sites stratified by baseline PD (i.e., 0-3 mm, 4-6 mm, > or =7 mm). Safety was evaluated using adverse event data and the results of clinical laboratory tests, oral pathology examinations, and microbiological assessments. Within each disease stratum, the incremental improvements in PD and CAL demonstrated in the SDD group over 9 months of active treatment were maintained through 3 additional months of no treatment. Treatment cessation did not result in an accelerated regression of periodontal health. No differences in the incidence of adverse events (including those related to infection) or laboratory or microbiological parameters were noted between the SDD group and the placebo group. The administration of SDD 20 mg bid for a period of up to 9 months is not associated with rebound effects or delayed or negative after-effects for a 3-month period after cessation of therapy.
    Journal Of Clinical Periodontology 09/2001; 28(8):782-9. · 3.69 Impact Factor
  • J Thomas, C Walker, M Bradshaw
    [Show abstract] [Hide abstract]
    ABSTRACT: Adjunctive subantimicrobial dose doxycycline (SDD) with scaling and root planing leads to improved clinical parameters of adult periodontitis, but has raised questions about potential changes in antibiotic susceptibility of the host microflora. Our four studies assessed whether long-term SDD changes antibiotic susceptibility of the oral microflora in adults with periodontitis. In studies 1 and 2, adult patients with periodontitis were randomized to receive SDD 10 mg qd, 20 mg qd, 20 mg bid, or placebo. In study 3, patients were randomized to receive SDD 20 mg bid or placebo. No medication was administered in study 4, a follow-up to study 3. Subgingival plaque samples were collected at baseline (all studies) and at 12, 15 to 18, and 24 months (study 1); 12, 18, and 27 months (study 2); 3, 6, and 9 months (study 3); and 3 months post-study 3 (study 4). Antimicrobial susceptibility of isolated bacteria was assessed by: 1) minimum inhibitory concentration (MIC) levels (studies 1 and 2); 2) cross-resistance to non-tetracycline antibiotics (studies 2 and 3); and 3) the proportion of doxycycline-resistant isolates (studies 3 and 4). Organism MIC levels remained constant among all treatment groups at 18 and 24 months compared with baseline (study 1). Observed changes in susceptibility at 12 and 18 months for the 20 mg groups were attributed to the limited number of isolates tested (study 1). There were no statistically significant differences in the proportion of doxycycline-resistant isolates among treatment groups (studies 3 and 4), and no evidence of multi-antibiotic resistance (studies 3 and 4) or cross-resistance (studies 2 and 3) at any timepoint. Long-term SDD does not contribute to changes in antibiotic susceptibility.
    Journal of Periodontology 10/2000; 71(9):1472-83. · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In a previous study, subantimicrobial dose doxycycline (SDD) significantly improved clinical parameters associated with periodontal health in patients with adult periodontitis (AP) when used as an adjunct to a maintenance schedule of supragingival scaling and dental prophylaxis. In this double-blind, placebo-controlled, parallel-group, multicenter study, the efficacy and safety of SDD were evaluated in conjunction with scaling and root planing (SRP) in patients with AP. Patients (n = 190) received SRP at the baseline visit and were randomized to receive either SDD 20 mg bid or placebo bid for 9 months. Efficacy parameters included the per-patient mean changes in clinical attachment level (CAL) and probing depth (PD) from baseline, the per-patient percentages of tooth sites with attachment loss (AL) > or = 2 mm and > or = 3 mm from baseline, and the per-patient percentage of tooth sites with bleeding on probing. Prior to analysis, tooth sites were stratified by the degree of disease severity evident at baseline In tooth sites with mild to moderate disease and severe disease (n = 183, intent-to-treat population), improvements in CAL and PD were significantly greater with adjunctive SDD than with adjunctive placebo at 3, 6, and 9 months (all P <0.05). In tooth sites with severe disease, the per-patient percentage of sites with AL > or = 2 mm from baseline to month 9 was significantly lower with adjunctive SDD than with adjunctive placebo (P<0.05). Improvements in clinical outcomes occurred without detrimental shifts in the normal periodontal flora or the acquisition of doxycycline resistance or multiantibiotic resistance. SDD was well tolerated, with a low incidence of discontinuations due to adverse events. The adjunctive use of SDD with SRP is more effective than SRP alone and may represent a new approach in the long-term management of AP.
    Journal of Periodontology 04/2000; 71(4):521-32. · 2.40 Impact Factor

Publication Stats

612 Citations
47.63 Total Impact Points

Institutions

  • 2004–2008
    • Newcastle University
      • School of Dental Sciences
      Newcastle upon Tyne, ENG, United Kingdom
    • Newcastle University Medicine Malaysia
      Bharu, Johor, Malaysia
  • 2002–2008
    • University of Kentucky
      Lexington, Kentucky, United States
  • 2007
    • Touro University College of Osteopathic Medicine
      Las Vegas, Nevada, United States
  • 2005
    • Covance
      Princeton, New Jersey, United States
  • 2001
    • Icon Clinical Research Inc
      North Wales, Pennsylvania, United States
  • 2000
    • West Virginia University
      Morgantown, West Virginia, United States