The use of antibiotics in nonsurgical periodontal treatment is indicated in cases in which scaling and root planing present important limitations. However, their use is controversial due to the secondary effects associated with them and the disagreements regarding their prescription. The aim of this study is to determine the effectiveness of systemic antibiotics in the management of aggressive and chronic periodontitis. The study was based on a search of randomized, controlled clinical trials. Common data were concentrated and evaluated by means of an analysis of variance (ANOVA), and a meta-analysis of the results was performed. The meta-analysis ( , 95% confidence interval, post hoc Bonferroni) determined that the supplementation of nonsurgical periodontal therapy with a systemic antibiotic treatment—amoxicillin with clavulanic acid and metronidazole or subantimicrobial dose doxycycline—provides statistically significant results in patients with aggressive or chronic periodontitis under periodontal treatment, whilst increasing the clinical attachment level of the gingiva and reducing periodontal probing depth. 1. Introduction It is now recognized that the majority of connective tissue and bone destruction in periodontal tissues occurs indirectly as a result of an excessive immunoinflammatory response in the host to the presence of bacterial plaque in susceptible individuals. Although bacterial pathogens initiate the periodontal inflammation, the host response to these pathogens is equally if not more important in mediating connective tissue breakdown, including bone loss [1, 2]. The host-derived enzymes known as matrix-degrading metalloproteinases (MMPs) as well as changes in osteoclast activity driven by cytokines and prostanoids catalyze the breakdown of proteins, including collagen, gelatin, proteoglycan core protein, fibronectin, laminin, and elastin, located either on the cell plasma membrane or within the extracellular matrix [3–6]. Pathologically excessive levels of activity of the various MMPs degrade all of the major components of the extracellular matrix in the gingiva, the periodontal ligament, and the alveolar bone, including the collagen fibers (mostly type I and III), proteoglycans, ground substance, and basement membranes [7–9]. The standard treatment for periodontitis remains highly nonspecific, consisting of the mechanical debridement of the affected root surface in order to reduce the total bacterial load and change the environmental conditions of these microbial niches [19]. However, not all patients nor all sites respond uniformly
References
[1]
S. S. Socransky, “Relationship of bacteria to the etiology of periodontal disease,” Journal of Dental Research, vol. 49, no. 2, pp. 203–222, 1970.
[2]
S. S. Socransky and A. D. Haffajee, “Microbial mechanisms in the pathogenesis of destructive periodontal diseases: a critical assessment,” Journal of Periodontal Research, vol. 26, no. 3, pp. 195–212, 1991.
[3]
L. M. Golub, K. Siegel, N. S. Ramamurthy, and I. D. Mandel, “Some characteristics of collagenase activity in gingival crevicular fluid and its relationship to gingival diseases in humans,” Journal of Dental Research, vol. 55, no. 6, pp. 1049–1057, 1976.
[4]
T. Berglundh, B. Liljenberg, and J. Lindhe, “Some cytokine profiles of T-helper cells in lesions of advanced periodontitis,” Journal of Clinical Periodontology, vol. 29, no. 8, pp. 705–709, 2002.
[5]
R. Górska, H. Gregorek, J. Kowalski, A. Laskus-Perendyk, M. Syczewska, and K. Madaliński, “Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis,” Journal of Clinical Periodontology, vol. 30, no. 12, pp. 1046–1052, 2003.
[6]
R. P. Teles, D. Sakellari, A. Konstantinidis, S. S. Socransky, and A. D. Haffajee, “Application of the checkerboard immunoblotting technique to the quantification of host biomarkers in gingival crevicular fluid,” Journal of Periodontology, vol. 80, no. 3, pp. 447–456, 2009.
[7]
L. M. Golub, T. F. McNamara, M. E. Ryan et al., “Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis,” Journal of Clinical Periodontology, vol. 28, no. 2, pp. 146–156, 2001.
[8]
A. R. Mohammad, P. M. Preshaw, M. H. Bradshaw, A. F. Hefti, C. V. Powala, and M. Romanowicz, “Adjunctive subantimicrobial dose doxycycline in the management of institutionalised geriatric patients with chronic periodontitis,” Gerodontology, vol. 22, no. 1, pp. 37–43, 2005.
[9]
J. Caton and M. E. Ryan, “Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD),” Pharmacological Research, vol. 63, no. 2, pp. 114–120, 2011.
[10]
J. G. Caton, S. G. Ciancio, T. M. Blieden et al., “Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis,” Journal of Periodontology, vol. 71, no. 4, pp. 521–532, 2000.
[11]
M. J. Novak, L. P. Johns, R. C. Miller, and M. H. Bradshaw, “Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe, generalized, chronic periodontitis,” Journal of Periodontology, vol. 73, no. 7, pp. 762–769, 2002.
[12]
P. M. Preshaw, A. F. Hefti, M. J. Novak et al., “Subantimicrobial dose doxycycline enhances the efficacy of scaling and root planning in chronic periodontitis: a multicenter trial,” Journal of Periodontology, vol. 75, no. 8, pp. 1068–1076, 2004.
[13]
P. M. Preshaw, M. H. Broadshaw, A. F. Hefti, C. V. Powala, and R. A. Ashley, “Adjunctive subantimicrobial dose doxicicline for treatment of smokers with periodontitis,” Journal of Dental Research, vol. 82, no. 1, supplement, p. B229, 2003.
[14]
A. Guerrero, G. S. Griffiths, L. Nibali et al., “Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial,” Journal of Clinical Periodontology, vol. 32, no. 10, pp. 1096–1107, 2005.
[15]
R. A. Reinhardt, J. A. Stoner, L. M. Golub et al., “Efficacy of sub-antimicrobial dose doxycycline in post-menopausal women: clinical outcomes,” Journal of Clinical Periodontology, vol. 34, no. 9, pp. 768–775, 2007.
[16]
I. Needleman, J. Suvan, M. S. Gilthorpe et al., “A randomized-controlled trial of low-dose doxycycline for periodontitis in smokers,” Journal of Clinical Periodontology, vol. 34, no. 4, pp. 325–333, 2007.
[17]
G. S. Griffiths, R. Ayob, A. Guerrero et al., “Amoxicillin and metronidazole as an adjunctive treatment in generalized aggressive periodontitis at initial therapy or re-treatment: a randomized controlled clinical trial,” Journal of Clinical Periodontology, vol. 38, no. 1, pp. 43–49, 2011.
[18]
P. M. Preshaw, M. J. Novak, J. Mellonig et al., “Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease,” Journal of Periodontology, vol. 79, no. 3, pp. 440–452, 2008.
[19]
R. P. Teles, A. D. Haffajee, and S. S. Socransky, “Microbiological goals of periodontal therapy,” Periodontology 2000, vol. 42, no. 1, pp. 180–218, 2006.
[20]
J. Slots and M. Ting, “Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment,” Periodontology 2000, vol. 20, no. 1, pp. 82–121, 1999.
[21]
AAP—American Association of Periodontology, “Parameter on “refractory” periodontitis,” Journal of Periodontology, vol. 71, no. 5, supplement, pp. 859–860, 2000.
[22]
A. P. V. Colombo, S. K. Boches, S. L. Cotton et al., “Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray,” Journal of Periodontology, vol. 80, no. 9, pp. 1421–1432, 2009.
[23]
P. Bidault, F. Chandad, and D. Grenier, “Systemic antibiotic therapy in the treatment of periodontitis,” Journal of the Canadian Dental Association, vol. 73, no. 6, pp. 515–520, 2007.
[24]
D. Herrera, M. Sanz, S. Jepsen, I. Needleman, and S. Roldán, “A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients,” Journal of Clinical Periodontology, vol. 29, no. 3, pp. 136–159, 2002.
[25]
A. B？umer, N. El Sayed, T. S. Kim, P. Reitmeir, P. Eickholz, and B. Pretzl, “Patient-related risk factors for tooth loss in aggressive periodontitis after active periodontal therapy,” Journal of Clinical Periodontology, vol. 38, no. 4, pp. 347–354, 2011.
[26]
A. D. Haffajee, S. S. Socransky, and J. C. Gunsolley, “Systemic anti-infective periodontal therapy. A systematic review,” Annals of Periodontology, vol. 8, no. 1, pp. 115–181, 2003.
[27]
M. Feres, A. D. Haffajee, K. Allard, S. Som, and S. S. Socransky, “Change in subgingival microbial profiles in adult periodontitis subjects receiving either systemically-administered amoxicillin or metronidazole,” Journal of Clinical Periodontology, vol. 28, no. 7, pp. 597–609, 2001.
[28]
C. Walter, E. M. Kulik, R. Weiger, N. U. Zitzmann, and T. Waltimo, “Additive or synergistic antimicrobial effects of amoxicillin and metronidazole on whole plaque samples: a preliminary report,” Journal of the International Academy of Periodontology, vol. 13, no. 1, pp. 11–16, 2011.
[29]
Y. Gu, H. M. Lee, T. Sorsa et al., “Non-antibacterial tetracyclines modulate mediators of periodontitis and atherosclerotic cardiovascular disease: a mechanistic link between local and systemic inflammation,” Pharmacological Research, vol. 64, no. 6, pp. 573–579, 2011.
[30]
K. Kotsillkov and Chr. Popova, “Effectiviness of target antimicrobial therapy of severe chronic periodontitis part III. Clinical attachment gain,” Journal Of IMAB, vol. 16, no. 4, pp. 24–26, 2010.
[31]
L. M. Golub, T. F. McNamara, G. D'Angelo, R. A. Greenwald, and N. S. Ramamurthy, “A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity,” Journal of Dental Research, vol. 66, no. 8, pp. 1310–1314, 1987.
[32]
L. M. Golub, S. Ciancio, N. S. Ramamurthy, M. Leung, and T. F. McNamara, “Low-dose doxycycline therapy: effect on ginigival and crevicular fluid collagenase activity in humans,” Journal of Periodontal Research, vol. 25, no. 6, pp. 321–330, 1990.
[33]
R. J. Crout, H. M. Lee, K. Schroeder et al., “The “Cyclic” regimen of low-dose doxycycline for adult periodontitis: a preliminary study,” Journal of Periodontology, vol. 67, no. 5, pp. 506–514, 1996.
[34]
R. Buchmann, M. E. Nunn, T. E. Van Dyke, and D. E. Lange, “Aggressive periodontitis: 5-year follow-up of treatment,” Journal of Periodontology, vol. 73, no. 6, pp. 675–683, 2002.
[35]
J. Lindhe and R. Palmer, “Group C summary,” Journal of Clinical Periodontology, vol. 29, no. 3, pp. 160–162, 2000.
[36]
J. B. Payne, J. A. Stoner, P. V. Nummikoski et al., “Subantimicrobial dose doxycycline effects on alveolar bone loss in post-menopausal women,” Journal of Clinical Periodontology, vol. 34, no. 9, pp. 776–787, 2007.
[37]
J. B. Payne and L. M. Golub, “Using tetracyclines to treat osteoporotic/osteopenic bone loss: from the basic science laboratory to the clinic,” Pharmacological Research, vol. 63, no. 2, pp. 121–129, 2011.
