title: Long-term use of subantimicrobial dose doxycycline does not lead to changes in antimicrobial susceptibility.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Long-term SDD does not contribute to changes in antibiotic susceptibility.
authors.affiliation: Department of Pathology/Periodontics, West Virginia University, Morgantown, USA. jthomas@hsc.wvu.edu
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: C
authors.initials: C
authors.lastname: Walker
authors.forename: M
authors.initials: M
authors.lastname: Bradshaw
mesh_terms: D000190:Actinomyces / Q000187:drug effects; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D016009:Chi-Square Distribution; D003773:Dental Plaque / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage*; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D005673:Fusobacterium / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016017:Odds Ratio; D010518:Periodontitis / Q000188:drug therapy* / Q000382:microbiology*; D018709:Statistics, Nonparametric; D013753:Tetracycline Resistance
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline