The present study shows that administration of an antibiotic regimen either immediately following mechanical therapy or 3 months after initial mechanical treatment resulted in reductions in pocket depth (PD) and clinical attachment (CAL) levels 6 months post-intial therapy. Moreover, the use of antibiotics immediately after mechanical therapy provided not only a more rapid decrease in PD, but also a more robust reduction in this clinical parameter. Interestingly, the delayed implementation of the antibiotic regimen still allowed for significant and equivalent reduction in CAL and inflammation levels (BoP and GCF markers) by 6 months post-initial therapy. When comparing clinical parameters 3 months following antibiotic treatment, no difference could be observed between groups, indicating that the antibiotic regimen is effective in reducing clinical parameters of disease once it is applied. The difference here lies in the time it takes for the major benefits to occur (total duration of treatment). The early prescription of antibiotics seems to result in a more rapid achievement and maintenance of the major clinical benefits. This is highlighted by the improvement in clinical parameters observed 3 months following immediate antibiotic intake. It is important to note the 3 month timepoint comparison is evaluating the effects of antibiotics versus non-antibiotics, since the delayed group (DelA) had yet to receive the antibiotic regimen. The favorable results with the use of antibiotics at this time point for the immediate antibiotic group (ImA) compared to the DelA group has also been reported by other investigators, using the same antibiotic combination (Sgolastra et al., 2011
, Mestnik et al., 2010
, Aimetti et al., 2012
A previous study (Kaner et al., 2007
) also observed advantages of immediate administration of the same regimen of antibiotics used in the current study, although for a slightly longer period of time, 10 days compared to 7 days used in the present study. Interestingly, these investigators also observed improved short-term (3 months) PD and CAL responses in the immediate antibiotic group. Furthermore, they reported additional benefits after delayed administration of antibiotics, which is also in agreement with the present findings. Although in both these studies, the two antibiotic regimens provided similar end results at 6 months, immediate antibiotic usage provided beneficial clinical responses earlier in the treatment, which persisted at 6 months. Since aggressive periodontitis is a relatively fast progressing disease, characterized by a hyper-inflammatory response (Shaddox et al., 2010
), earlier reduction of bacterial insult and inflammatory processes may be beneficial to hamper the disease progression.
A possible explanation for the greater benefits of the immediate application of antibiotics in aggressive periodontitis could be the fact that the combination of amoxicillin and metronidazole may provide immediate reduction of putative periodontopathogens such as A.actinomycetemcomitans
from within tissues, whereas SRP may have limited ability to do so, as reported in previous studies (Xajigeorgiou et al., 2006
, van Winkelhoff et al., 1992a
, Renvert et al., 1990
). This inability to remove important bacteria from within tissues could possibly enable these “invading” organisms to re-colonize the pocket and maintain a continuous insult to the host. In addition, antibiotics will also help control re-colonization of the lesion with commensal/non-pathogens which under normal circumstances would not induce robust immune response, but could potentially aggravate an ongoing pathogenic inflammatory response. Antibiotics allow for not only clearance of pathogens, but also provide time for the host’s inflammatory recovery before bacterial re-colonization occurs. Persistent bleeding and higher levels of inflammatory markers after SRP presented by the delayed antibiotic group in the present study could have been a result of this continuous “induction” of the host’s inflammatory process by the present bacteria. Once antibiotics were applied in the immediate group, an initial significant reduction of clinical parameters and inflammatory markers was observed and maintained for 6 months. On the other hand, the delayed group only obtained mild reductions in inflammatory markers and clinical parameters initially after SRP, but once antibiotics were administered, additional reductions were observed. One exception was IL8, which was increased in the ImA group at both time points. This chemokine is known to induce chemotaxis for innate immune cells, i.e. neutrophils. In addition, IL8 also plays an important role in the process of wound healing, which could explain its higher levels in the early antibiotic usage group. This early and more robust reduction in pro-inflammatory response, coupled with an elevated anti-inflammatory response, could have contributed to early improvement in clinical parameters observed in the immediate antibiotic group. Similar results in local inflammatory markers after treatment with antibiotics have been reported previously (de Lima Oliveira et al., 2012
). Thus, the immediate application of antibiotics may be more beneficial for the treatment of this type of aggressive inflammatory process.
Different antibiotic regimens have been studied in periodontal disease therapy, including aggressive periodontitis (Haffajee et al., 2003
). There seems to be no consensus on which antibiotic or specific dosages is most effective. The current study employed the combination of amoxicillin 500mg and metronidazole 250mg because it had been studied previously, where effective results in the treatment of both chronic and aggressive periodontitis were observed (Winkel et al., 2001
, van Winkelhoff et al., 1992b
, van Winkelhoff et al., 1989
, Kaner et al., 2007
, Aimetti et al., 2012
). Since the cohort of the current study consisted of young participants, the lower dose of metronidazole (250mg) was utilized, where no side effects have been reported as of yet. This antibiotic choice was also effective in reducing mean PD at 3 and 6 months post-therapy in the ImA group (1.37 ±1.06 and 1.86 ± 0.93, respectively), which is similar to what has been reported by Kaner et al 2007
(mean PD reduction of 1.85 and 1.95 at 3 and 6 months, respectively), using a similar antibiotic regimen. The magnitude of gain in the current study was slightly smaller compared to that reported by Kaner et al. This could be attributed to the slightly longer antibiotic regimen used by Kaner et al (10 days versus 7 days on the present study) along with slightly different diagnosis and cohort age (generalized aggressive and mean age 34 versus localized and mean age 13 in the present study).
Some limitations are associated with the present study. For instance, this was a retrospective evaluation and not a randomized trial. While retrospective analyses are helpful in understanding treatment effects, randomized controlled trials need to be conducted to confirm the benefits of immediate antibiotic administration. The present study was conducted within the same clinic and within a homogeneous population with very similar diseased characteristics. In addition, examinations and treatments of both groups were performed by the same group of calibrated investigators, which is clearly an advantage on the conduct of a retrospective study. Although both therapists were experienced and calibrated to the treatments and both treated patients in both experimental groups, one may argue that their individual clinical judgment used to determine extent of therapy could have been a possible source of bias. Previous studies, however, have shown similar clinical results when comparing non-surgical treatment by different experienced operators (Badersten et al., 1981b
, Badersten et al., 1984b
). An additional limitation includes the inability to evaluate the specific response for deep and moderate pockets since LAP disease is localized to a limited number of teeth. Finally, this study is only powered to detect differences of 1mm or greater between groups, which is considered a clinically significant difference. However, potential smaller differences remaining between groups at 6 months could have been missed in the present investigation. Thus, longer follow-up with a greater number of subjects is still warranted to confirm the present findings.
Within the limitations of the present study, we conclude that although both treatment regimens result in satisfactory clinical results at 6 months, immediate systemic antibiotic application seems to be more advantageous in the treatment of localized aggressive periodontitis, as it results in an earlier greater improvement in clinical parameters and local inflammatory response when compared to delayed antibiotic use.