The effect of azithromycin on the non-surgical treatment of peri-implantitis. A prospective double blind placebo controlled randomised clinical trial. A pilot study

Abstract

3.0 Abstract 3.1 Aim The aim of this study is to determine in a randomized control trial the microbiological and immunological effect of azithromycin (AZM) in cases of peri-implantitis versus a placebo at the peri-implant tissue level in a sample of patients diagnosed with peri-implantitis. 3.2 Methodology 17 patients referred to periodontics department at the Westmead Centre for Oral Health for the treatment of peri-implantitis were invited to participate in the study. Five subjects with healthy implants were also recruited for the immuno-regulatory part of the study to act as healthy controls. After clinical assessment, subjects received non-surgical debridement of implant/abutment surfaces and oral hygiene instruction. The subjects were then randomly assigned to receive AZM (1 x 500mg capsule per day for 3 days) and the controls received placebo tablets. Submucosal plaque and peri-implant crevicular fluid samples were collected from selected implants at the following time points: day 0, 3, 7, 21, 90 and 180 for microbiological and immunological analysis. The primary outcome variables were mean counts and mean changes from baseline levels in the anaerobic and aerobic microbiological counts (CFU/ml) and the proinflammatory cytokine Il-1β levels (pg/ml) over time. Analysis of the species associated with peri-implantitis and the cytokine levels of healthy control implants was also determined. 7 3.3 Results The placebo group showed a trend for aerobic bacteria to steadily rebound after day 7. This rebound appeared to be delayed until day 90 in the azithromycin group. Both treatment groups showed a trend for the mean anaerobic bacteria count to decrease from day 1 to 7 after which a gradual increase in counts was observed for the remainder of the study. The magnitude of this rebound in anaerobic bacteria levels was greater in the placebo group. There were no statistical significant differences observed between the two groups at any times points (p>0.05). The placebo group showed a mean change from baseline resulting in reduction in anaerobic bacteria counts up to day 7, after which a rebound in bacteria levels were observed above baseline levels and sustained throughout the remainder of the study. The azithromycin group showed mean changes from baseline levels resulting in a sustained decrease in mean anaerobic bacteria levels below baseline observed up 180 days. No statistical significant differences observed between the two groups at any times points (p>0.05). Orange complex species were found in the highest frequency (94.1%) whilst the red complex bacteria were found at the lowest frequency (17.6%) with no statistical significant differences between treatment groups observed at baseline. Both groups demonstrated a trend for mean reduction in IL-1β levels after treatment over time which was sustained throughout the study. The magnitude of changes from baseline levels appeared greater in the azithromycin group. No statistical significance was observed between treatment groups (p>0.05). It was observed that the percentage frequency of subjects who were “positive responders” was higher in the azithromycin group at all time points. 8 3.4 Conclusion The reductions and subsequent recolonization observed in the immunological data closely correlated with that of the microbiological data. Despite reductions in levels of IL-1β initially after treatment, the levels gradually rebounded throughout the course of the study. Throughout all time points, IL-1β did not return to baseline levels, which were likely a result of the treatment effect. Similarly, a reduction in microbiological parameters was seen initially post therapy with a trend for a gradual rebound in counts seen over time. No statistical significant effect was observed between treatment groups despite a trend for a greater magnitude change in outcome measures for subjects’ allocated azithromycin. We demonstrated that the response to non-surgical treatment, with or without adjunctive azithromycin is highly variable and unpredictable with gradual rebound in immunological and microbiological parameters seen after 6 months. Because of the limited number of patients recruited, no definitive conclusions can be made. There is clear indication that further longitudinal research into the effects of azithromycin at peri-implant-host interface is warranted.