Long-term use of subantimicrobial dose doxycycline does not lead to changes in antimicrobial susceptibility

Background: Adjunctive subantimicrobial dose doxycycline (SDD) with scaling and root planing leads to improved clinical parameters of adult periodonti tis, but has raised questions about potential changes in antibiotic suscept ibility of the host microflora. Our four studies assessed whether long-term SDD changes antibiotic susceptibility of the oral microflora in adults wit h periodontitis. Methods: In studies 1 and 2, adult patients with periodontitis were randomi zed to receive SDD 10 mg qd, 20 mg qd, 20 mg bid, or placebo. In study 3, p atients 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 sam ples were collected at baseline (all studies) and at 12, 15 to 18, and 24 m onths (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 i solated bacteria was assessed by: 1) minimum inhibitory concentration (MIC) levels (studies 1 and 2); 2) cross-resistance to non-tetracycline antibiot ics (studies 2 and 3); and 3) the proportion of doxycycline-resistant isola tes (studies 3 and 4). Results: Organism MIC levers remained constant among all treatment groups a t 18 and 24 months compared with baseline (study 1). Observed changes in su sceptibility at 12 and 18 months for the 20 mg groups were attributed to th e 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-antibio tic resistance (studies 3 and 4) or cross-resistance (studies 2 and 3) at a ny timepoint. Conclusion: Long-term SDD does not contribute to changes in antibiotic susc eptibility.