Adjunctive Benefits of Systemic Amoxicillin and Metronidazole In
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J Clin Periodontol 2005; 32: 1096–1107 doi: 10.1111/j.1600-051X.2005.00814.x Copyright r Blackwell Munksgaard 2005 Adrian Guerrero1,2, Gareth S. Griffiths1, Luigi Nibali1, Jean Suvan1, Adjunctive benefits of systemic 1 1 David R. Moles , Lars Laurell and Maurizio S. Tonetti1 amoxicillin and metronidazole in 1Department of Periodontology and Eastman Clinical Investigation Centre, Eastman Dental Institute and Hospital, University College non-surgical treatment of London, London, UK; 2Private Periodontal Practice, Malaga, Spain generalized aggressive periodontitis: a randomized placebo-controlled clinical trial Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, Tonetti MS. Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo controlled clinical trial. J Clin Periodontol 2005; 32: 1096–1107. doi: 10.1111/j.1600-051X. 2005.00814.x. r Blackwell Munksgaard 2005. Abstract Background: The objective of this study was to assess the adjunctive clinical effect of the administration of systemic amoxicillin and metronidazole in the non-surgical treatment of generalized aggressive periodontitis (GAP). Methods: Forty-one systemically healthy subjects with GAP were included in this 6-month double-blind, placebo-controlled, randomized clinical trial. Patients received a course of full-mouth non-surgical periodontal treatment delivered over a 24 h period using machine-driven and hand instruments. Test subjects received an adjunctive course of systemic antibiotic consisting of 500 mg amoxicillin and 500 mg metronidazole three times a day for 7 days. Clinical parameters were collected at baseline, and at 2 and 6 months post-treatment. Results: In both the test and the placebo groups, all clinical parameters improved at 2 and 6 months. In deep pockets (X7 mm), the test treatment resulted in an additional 1.4 mm (95% confidence interval 0.8, 2.0 mm) in full-mouth probing pocket depth (PPD) reduction and 1 mm (0.7, 1.3 mm) of life cumulative attachment loss (LCAL) gain at 6 months. In moderate pockets (4–6 mm), the adjunctive benefit was smaller in magnitude: PPD reduction was 0.4 mm (0.1, 0.7 mm) and LCAL gain was 0.5 mm (0.2, 0.8 mm). In addition, the 6-month data showed LCAL gains X2 mm at 25% of sites in test patients compared with 16% in placebo (p 5 0.028). Similarly, PPD reductions of 2 mm or more were observed in 30% of sites in test and 21% of sites in placebo patients. Seventy-four percent of pockets with PPD X5 mm at baseline were 4 mm or shallower at 6 months in the test group. This compared with 54% in the placebo group (p 5 0.008). Disease progression at 6 months was observed at 1.5% of test and 3.3% of sites in test and placebo, respectively (p 5 0.072). Key words: antibiotics; generalized aggressive periodontitis; human; randomized-controlled Conclusions: These data indicate that a 7-day adjunctive course of systemic clinical trial; treatment metronidazole and amoxicillin significantly improved the short-term clinical outcomes of full-mouth non-surgical periodontal debridement in subjects with GAP. Accepted for publication 1 June 2005 1096 Treatment of generalized aggressive periodontitis 1097 Generalized aggressive periodontitis the benefits achieved could not be con- performed including a full medical and (GAP) affects a minority of periodontal firmed as attributable to the adjunctive dental history, an intra-oral examination patients but is highly significant because antibiotic. and a full-mouth periodontal probing. it is characterized by severe destruction Recent investigations, performed in A radiographic examination was under- of the supporting apparatus of the teeth, chronic periodontitis patients, have indi- taken using either periapicals or a which may lead to edentulism early in cated that full-mouth scaling and root pantomogram. A periodontal diagnosis life. Because of its relatively rare occur- planing within 24 h (FSR) results in was made, and subjects who fulfilled the rence, few studies have evaluated how to different degrees of clinical and micro- study inclusion/exclusion criteria were treat this condition. The current notion is biological additional benefits (Quirynen provided with a written information that, as with most forms of periodontitis, et al. 1995, Bollen et al. 1996, Vande- sheet, related to the study protocol, and the first step in the treatment of GAP is a kerckhove et al. 1996, Mongardini et al. they were invited to participate in the cause-related treatment phase aimed at 1999, Apatzidou & Kinane 2004). The study. the reduction and/or elimination of the benefits of this approach have not been The study included subjects with (i) pathogenic microflora. systematically evaluated in aggressive GAP (according to the criteria of the In recent years, two approaches have periodontitis patients but initial data in 1999 international classification (Armi- been introduced to improve the clinical chronic periodontitis patients suggest tage 1999); (ii) at least 20 teeth present; outcomes of cause-related periodontal that the full-mouth scaling within 24 h (iii) good general health and (iv) age therapy in chronic periodontitis patients: may perform as well as the conven- between 16 and 35 when first diagnosed the use of adjunctive antibiotics, and tional treatment (Apatzidou & Kinane with aggressive periodontal disease. performing debridement within a 24 h 2004, Kinane 2005, Koshy et al. 2005, Subjects were excluded from the study period, the so-called ‘‘full-mouth disin- Wennstrom et al. 2005). In addition, if they: (i) were considered to have a fection’’ approach (Quirynen et al. 1995). some potential benefits, such as the diagnosis of chronic periodontitis The adjunctive use of systemic anti- application of a better understanding of (according to the criteria of the 1999 biotics is supported by evidence pub- the infectious process, a reduced num- international classification (Armitage lished in systematic reviews of trials ber of treatment sessions for patients, a 1999); (ii) were pregnant or lactating assessing the benefit of systemic anti- more efficient use of treatment time and females; (iii) were females of child- biotics in cases with advanced perio- a reduced cost of therapy, may all be in bearing age not using a standard dontitis (Herrera et al. 2002, Haffajee favour of the FSR (Greenstein 2002). accepted method of birth control; (iv) et al. 2003). Among the possible regi- The aim of this double-blind rando- required antibiotic pre-medication for mens, the combination of amoxicillin mized placebo-controlled study was to the performance of periodontal exami- and metronidazole has gained increasing test the null hypothesis of ‘‘no differ- nation and treatment; (v) suffered from popularity because of its wide spectrum ence in treatment effect of adjunctive any other systemic diseases (cardiovas- of activity and effectiveness in terms of use of systemic amoxicillin plus metro- cular, pulmonary, liver, cerebral, dis- suppression of Actinobacillus actinomy- nidazole during full-mouth non-surgical eases or diabetes); (vi) had received cetemcomitans (Van Winkelhoff et al. cause-related periodontal treatment antibiotic treatment in the previous 3 1989), possibly because of a synergistic (FSR) performed within 24 h compared months; (vii) were taking long-term effect of the combination of amoxicillin with FSR alone, in patients with GAP anti-inflammatory drugs; (viii) had and metronidazole against A. actinomy- patients at 2 and 6 months after the received a course of periodontal treat- cetemcomitans that has been demon- completion of active treatment. ment within the last 6 months; (ix) were strated in vitro (Pavicic et al. 1991, allergic to penicillin or metronidazole; 1994a, b). In addition, chronic perio- and (x) were not able to provide consent dontitis patients harbouring subgingival Material and Methods to participate in the study, or they did Porphyromonas gingivalis benefit sig- Experimental design not accept the proposed treatment plan. nificantly from the combined therapy Informed consent was obtained from all (Winkel et al. 2001). Randomized-con- This study was a randomized placebo- the subjects to be entered in the study. trolled clinical trials have reported clin- controlled, parallel-design, double-blind ical and microbiological improvements clinical trial with 6-month follow-up. Pre-treatment in chronic periodontitis patients treated Ethical approval was obtained from the with these two antibiotics (Berglundh Eastman Dental Institute University All the subjects went through motiva- et al. 1998, Flemmig et al. 1998, Winkel College London Hospitals joint Re- tion sessions during which oral hygiene et al. 2001, Rooney et al. 2002). Further- search and Ethics Committee, and the instructions were given. The purpose of more, some clinical studies have study was conducted according to the these sessions was to ensure that the reported good long-term clinical out- principles outlined in the Declaration of subjects could maintain a proper level of comes in patients with ‘‘severe disease Helsinki on experimentation involving oral hygiene before starting active treat- which was associated with A. actinomy- human subjects. ment, and this was repeated until sub- cetemcomitans’’ (Van Winkelhoff et al. jects showed the ability to maintain 1992, Pavicic et al. 1994a, Winkel et al. good plaque control as evidenced by Population screening 1998) and in aggressive periodontitis pre-treatment plaque scores o20%. (Buchmann et al.