Microbial Assessment of Chlorhexidine Diacetate Delivery System: Phase I Trial

Chlorhexidine diacetate (CDA) has been incorporated (2.5% by weight) into an ethylene vinyl acetate (EVA) intraoral delivery system for the proposed treatment indication of HIV-associated periodontitis. In vitro testing indicates sustained CDA delivery for at least 14 days. Objectives: 1) To evaluate changes in the oral biofilm with CDA treatment in medically healthy subjects with gingivitis. 2) To evaluate susceptibility patterns of plaque samples before, during and after CDA treatment. Methods: Six adult subjects with moderate plaque-induced gingivitis were recruited for this open-label, phase I trial. CDA-EVA mouthguards were fabricated to fit the maxillary arches of subjects and worn 12 hours/day for 21 days. Microbiological samples (subgingival, buccal mucosa and tongue dorsum) were obtained at Days 0 (pre-dosing), 7 and 35, and cultured using selective and differential media under appropriate atmospheres. Zones of inhibition were measured for CDA resistance formation using disks (6mm in diameter) from standard 2.5% CDA-EVA films placed on agar surfaces inoculated with subjects' subgingival plaque samples. When only a portion of the bacteria were inhibited, zones of partial inhibition were also measured. Results: CDA treatment significantly decreased both aerobic (Day 0 vs. Day 7, p=0.05; Day 0 vs. Day 35, p=0.01) and anaerobic (Day 0 vs. Day 35, p=0.01). bacteria. In general, CDA treatment resulted in mean decreases in red and orange complex bacteria. No significant changes were observed for mean zones of total or partial inhibition. Conclusion: CDA treatment does not alter the CDA-susceptibility profile of oral flora and may reduce aerobic and anaerobic bacteria. A phase II trial in HIV subjects may proceed. [Supported by DE15267-01, RR00046]