Nigerian Journal of Clinical Practice

ORIGINAL ARTICLE
Year
: 2015  |  Volume : 18  |  Issue : 4  |  Page : 506--510

Effects of azithromycin versus metronidazole-amoxicillin combination as an adjunct to nonsurgical periodontal therapy of generalized aggressive periodontitis


E Ercan, BC Uzun, G Ustaoglu 
 Department of Periodontology, Karadeniz Technical University, Trabzon, Turkey

Correspondence Address:
E Ercan
Department of Periodontology, Karadeniz Technical University, 61080 Trabzon
Turkey

Abstract

Objective: This study evaluated the short-term clinical benefits of two systemic antibiotic regimes added to the nonsurgical periodontal treatment of generalized aggressive periodontitis. Materials and Methods: The patient records were reviewed and 45 patients were selected and divided into the following three groups: Scaling and root planning (SRP) only; SRP plus azithromycin (AZT group); and SRP plus metronidazole and amoxicillin (M + A group). The periodontal indexes were recorded at baseline and 3-month posttherapy. Results: The periodontal parameters were improved in all groups 3-month posttherapy. The scores were decreased more in the AZT and M + A groups than the controls, but this difference did not reach significance. In addition, the decrease in the plaque index from baseline to 3-month in the AZT group was not significant. Conclusion: Nonsurgical therapy reduces the probing depth, clinical attachment level, and clinical inflammation findings. This healing tendency was observed in the AZT group despite the baseline plaque scores. Therefore, AZT might be active against the bacteria in dental biofilms.



How to cite this article:
Ercan E, Uzun B C, Ustaoglu G. Effects of azithromycin versus metronidazole-amoxicillin combination as an adjunct to nonsurgical periodontal therapy of generalized aggressive periodontitis.Niger J Clin Pract 2015;18:506-510


How to cite this URL:
Ercan E, Uzun B C, Ustaoglu G. Effects of azithromycin versus metronidazole-amoxicillin combination as an adjunct to nonsurgical periodontal therapy of generalized aggressive periodontitis. Niger J Clin Pract [serial online] 2015 [cited 2021 Sep 26 ];18:506-510
Available from: https://www.njcponline.com/text.asp?2015/18/4/506/154221


Full Text

 Introduction



Generalized aggressive periodontitis (GAP) is a complex periodontal disease affecting the entire dentition with pronounced, rapid destruction of the periodontium and resulting loss of teeth. [1] Unlike chronic periodontitis, the amount of biofilm and calculus accumulation is consistent with the severity and progression of the periodontal destruction because of an inadequate host response to periodontopathogenic bacteria, [2],[3] and is characterized by the episodic, rapid destruction of periodontal tissues.

The primary approach to the treatment of GAP is surgical and nonsurgical mechanical treatment. To enhance the outcome of nonsurgical therapy, including scaling and root planning (SRP), antimicrobial agents have been used as adjuncts to conventional periodontal therapy. [4] There is a consensus that the use of adjunctive antibiotics results in greater attachment levels than mechanical therapy alone. [5],[6] However, there is little consensus on the optimum type, dosage, duration of treatment, and mix of antibiotics for combination therapy. [7]

The combined use of amoxicillin (AMX) and metronidazole (MTZ) has been proposed to exhibit increased bactericidal, and spectral efficacy compared with monotherapy with either drug. [8],[9] The combination of MTZ and AMX in the treatment of aggressive periodontitis has gained recognition mostly due to its effectiveness against Aggregatibacter actinomycetemcomitans, a periodontal pathogen closely associated with the etiology of this infection. [10],[11] In addition to A. actinomycetemcomitans, this combination is active against Treponema denticola, Tannerella forsythia, Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia. [12],[13],[14]

Azithromycin (AZT) is a macrolide antibiotic that has more potent activity against Gram-negative bacteria compared with erythromycin, can penetrate dental biofilms, and has good periodontal tissue penetration. [15],[16],[17],[18] Higher concentrations persist in many tissues for 0-7 days using a simple dosage regimen. [15],[19] The effectiveness of adjunctive AZT in the treatment of chronic and aggressive periodontitis has been investigated. [20],[21],[22] However, there is no clear protocol for the use of antibiotics as adjuncts to the nonsurgical treatment of GAP. Therefore, this retrospective study determined the clinical short-term effects of AZT and a combination of MTZ and AMX.

 Materials and Methods



The study protocol was approved by the Ethics Committee of Karadeniz Technical University. The clinical records of GAP patients seen from 2010 to 2013 in the Department of Periodontology were reviewed to identify patients diagnosed with "GAP" according the criteria of Armitage, [1] who were nonsmokers, systemically healthy, with no medication use in the previous 6 months, and no previous periodontal treatment. The records of 93 patients were examined; 45 met the inclusion criteria. The following clinical parameters were scored at six sites per tooth (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, and distolingual) at baseline and 12 weeks after SRP: Probing depth (PD), clinical attachment level (CAL), gingival index (GI), plaque index (PI), and bleeding on probing (BOP). The control group underwent full-mouth SRP only, whereas the two test groups received one of the two systemic antibiotic regimens in addition to SRP. The first test group (AZT group; n = 15) was given AZT 500 mg, once per day, for 3 days, and the second group was given MTZ + AMX 500 mg each, 3 times/day (M + A group; n = 15).

Statistical analysis

The Kolmogorov-Smirnov test was used to evaluate the parameter distributions; all parameters were distributed normally. Therefore, parametric tests were used for further statistical comparisons. The gender and age distributions among the groups were analyzed using Pearson's Chi-square test and one-way analysis of variance (ANOVA), respectively. Intra-group differences were tested using paired t-tests. Initial values and the mean changes in the parameters examined were compared by one-way ANOVA. Tukey's honestly significant difference (HSD) test was performed as a post-hoc assessment of individual differences. All statistical analyses were performed using SPSS for Windows 8, version 13.0 (SPSS, Chicago, IL, USA). Statistical significance was accepted at P < 0.05.

 Results



[Table 1] presents the mean baseline clinical characteristics. There were no significant differences among groups in terms of age, gender, or clinical periodontal parameters, confirming that the groups were well matched.{Table 1}

The mean per-group average change in periodontal parameters from baseline to 3 months after SRP is shown in [Table 2]. There were clinical improvements in almost all parameters at 3 months for all groups. The PD, CAL, GI, and BOP were reduced significantly in all groups. The PI also showed a significant clinical improvement for the M + A and C groups (-0.71 ± 0.64, P 0˂ 0.01 and -0.58 ± 0.44, P ˂ 0.001, respectively). However, PI did not change significantly at 3 months in the AZT group (-0.19 ± 0.61, P 0≥ 0.05). All of the treatment protocols significantly reduced the PD in all groups. However, an additional reduction in PD was seen in the test groups compared with the control group (-1.29 ± 1.39, -1.27 ± 0.51, and -0.79 ± 0.55, for AZT, M + A, and C, respectively). A similar trend was seen for CAL; the control group showed less attachment gain than the test groups, but the differences among groups were not significant (-1.56 ± 1.74, -1.56 ± 0.96, and -0.79 ± 0.69 for AZT, M + A, and C, respectively).{Table 2}

The clinical periodontal parameters are shown in [Table 3]. There were no significant differences in the reductions in the clinical parameters in all cases, with the exception of the difference in the reduction in PI between groups AZT and M + A.{Table 3}

 Discussion



This study assessed the short-term clinical benefits of two treatment protocols for nonsurgical periodontal therapy of GAP. Many studies have compared antibiotic regimens as adjuncts to SRP. [23],[24],[25],[26] We reviewed their findings to assess the use of antimicrobials administered after an initial period of oral hygiene motivation.

Our study comprised a control and two test groups. There were no differences among groups in terms of age, gender, and initial periodontal parameters. All patients were nonsmokers. Our data indicate that all three therapies improved the PD, CAL, GI, and BOP at the 3-month follow-up.

Scaling and root planning is an essential initial therapy to induce the resolution of inflammation via the removal of plaque, calculus, and endotoxins from the root surfaces. In our series, all clinical parameters improved in the control group. In most clinical studies, M + A combined with SRP leads to significantly greater reductions in clinical periodontal parameters. [23],[25],[27],[28] Guerrero et al. assessed the adjunctive benefits of M + A in the nonsurgical treatment of GAP and found that all clinical parameters were improved at 2 and 6 months in both the test and placebo groups. [25] Regarding deep pockets, however, the M + A therapy resulted in an additional 1.4-mm PD and 1-mm CAL gain. Similarly, Casarin et al. treated GAP patients with full-mouth ultrasonic debridement with or without administering M + A. [23] Their results showed the clinical and microbiological benefits of M + A administration 3 and 6 months posttherapy. The PD reductions were 3.99 ± 1.16 and 3.09 ± 0.78 in the test and control groups, respectively. In another study, aggressive periodontitis was treated similarly, using M + A in addition to nonsurgical treatment; the use of M + A resulted in additional clinical benefits. [28] In that study, the PD decreased from 3.5 ± 0.7 to 2.5 ± 0.5 mm at 12 weeks. In addition, the gingival bleeding index, plaque control record, and BOP all decreased significantly. Silva-Senem et al. also showed significant clinical improvements in most parameters at 1-year in the nonsurgical treatment of GAP patients with or without M + A, although the M + A group had shallower residual pockets than the placebo group. [29] Another randomized, controlled, clinical trial evaluated the short-term effects of nonsurgical treatment of aggressive periodontitis with M + A and photodynamic therapy (PT); both treatments improved the clinical parameters after 3-month, although the systemic administration of antibiotics resulted in a greater reduction in PD compared to the PT group. [30]

Our results were similar to these reports in that the clinical periodontal parameters improved in both the M + A and control groups. The PD was reduced significantly (P ˂ 0.001) by 1.27 ± 0.51 and 0.79 ± 0.55 for the respective groups. The reduction was greater in the M + A group. Similar healing tendencies were observed for the other parameters. Therefore, both treatment protocols helped to resolve the periodontal inflammation. The differences were greater in the M + A group, albeit not significantly so.

Recently, AZT has been administered as an adjunctive antimicrobial in the treatment of periodontal disease. Several studies have evaluated the benefits of AZT, [7],[20],[22],[26],[31],[32] although fewer have evaluated the clinical benefits of AZT in GAP. Haas et al. treated 24 subjects with SRP with or without the administration of 500-mg AZT once per day for 3 days. [26] They showed a reduction in PD and improvement in the CAL in both groups from baseline to 12 months. However, the test group showed a significantly greater reduction in PD and a higher percentage of attachment gain. Emingil et al. treated 32 GAP patients with nonsurgical therapy with or without AZT and found that all clinical parameters improved, and the microbiological parameters and gingival crevicular fluid matrix metalloproteinase-8 levels decreased significantly in both groups. [33] They found that AZT exerts no beneficial effect compared to nonsurgical periodontal therapy in GAP patients. In 2010, Hirsch reported three cases of chronic or aggressive periodontitis who received AZT adjunctive to nonsurgical treatment; in all cases the periodontal inflammation resolved and pocket depth decreased. [7] Han et al. examined the efficacy of AZT in combination with nonsurgical periodontal therapy for 6 months in generalized chronic periodontitis patients; AZT and placebo resulted in similar significant improvements in all clinical parameters. [34] In addition, in both groups, numbers of A. actinomycetomcomitans, P. gingivalis, T. forsythia, P. intermedia, and total bacteria were reduced at 6 months. The levels of F. nucleatum decreased significantly at all visits in the test group. Therefore, adjunctive AZT provides no additional benefits over a placebo for GAP.

In our study, the clinical periodontal parameters healed significantly in the AZT group. When we compared whole groups, the parameters improved similarly. However, the reduction in PD was higher in the AZT group than the controls, albeit not significantly so (-1.29 ± 1.39, -1.27 ± 0.51, and -0.79 ± 0.55 for the AZT, M + A, and control groups, respectively). The CAL, GI, and BOP showed similar tendencies to the PD. The PI also decreased compared to baseline, albeit not significantly so. AZT is active against the bacteria in dental plaque, [16] which might be an advantage. Although clinicians attempt to motivate, patients to perform plaque control, maintaining a high level of oral hygiene can be difficult. Thus, AZT administration might be useful for the treatment of periodontitis.

Mechanical treatment may not be effective on periodontal pathogens such as A. actinomycetomcomitans at inaccessible areas and periodontal soft tissues. [6] Therefore, patients with aggressive periodontitis may provide benefits from the adjunctive use of antibiotics adjunct to treatment. There are various antibiotic regimes that recommended for the treatment of GAP. We compared two of them and in our knowledge; this is the first study that compared the AZT and M + A combination adjunct to SRP. Hence, the results may be a useful guide about the choice of antibiotics. In addition, the patient records were selected meticulously for this study. The GAP patients had been treated in the same clinic, by the same treatment protocol and by previously standardized, experienced clinicians. Hence, the differences between treatment protocols were eliminated and gave us the chance to obtain more homogenous data.

However, there were several limitations to this study, including the short follow-up time and the fact that no immunological or microbiological parameters were evaluated. Further research is needed to identify the optimum adjunctive antibiotic therapy for the nonsurgical treatment of GAP.

 Acknowledgment



Thanks to Dr. Mevlut Celikoglu for his kindly supports for statistical analaysis.

References

1Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4:1-6.
2Parameter on aggressive periodontitis. American Academy of Periodontology. J Periodontol 2000;71 5 Suppl: 867-9.
3Meng H, Xu L, Li Q, Han J, Zhao Y. Determinants of host susceptibility in aggressive periodontitis. Periodontol 2000 2007;43:133-59.
4Ramberg P, Rosling B, Serino G, Hellström MK, Socransky SS, Lindhe J. The long-term effect of systemic tetracycline used as an adjunct to non-surgical treatment of advanced periodontitis. J Clin Periodontol 2001;28:446-52.
5Haffajee AD, Socransky SS, Gunsolley JC. Systemic anti-infective periodontal therapy. A systematic review. Ann Periodontol 2003;8:115-81.
6Prakasam A, Elavarasu SS, Natarajan RK. Antibiotics in the management of aggressive periodontitis. J Pharm Bioallied Sci 2012;4:S252-5.
7Hirsch R. Periodontal healing and bone regeneration in response to azithromycin. Aust Dent J 2010;55:193-9.
8Pavicic MJ, van Winkelhoff AJ, Douqué NH, Steures RW, de Graaff J. Microbiological and clinical effects of metronidazole and amoxicillin in Actinobacillus actinomycetemcomitans-associated periodontitis. A 2-year evaluation. J Clin Periodontol 1994;21:107-12.
9Griffiths GS, Ayob R, Guerrero A, Nibali L, Suvan J, Moles DR, et al. Amoxicillin and metronidazole as an adjunctive treatment in generalized aggressive periodontitis at initial therapy or re-treatment: A randomized controlled clinical trial. J Clin Periodontol 2011;38:43-9.
10Winkel EG, Van Winkelhoff AJ, Timmerman MF, Van der Velden U, Van der Weijden GA. Amoxicillin plus metronidazole in the treatment of adult periodontitis patients. A double-blind placebo-controlled study. J Clin Periodontol 2001;28:296-305.
11Kaner D, Bernimoulin JP, Hopfenmüller W, Kleber BM, Friedmann A. Controlled-delivery chlorhexidine chip versus amoxicillin/metronidazole as adjunctive antimicrobial therapy for generalized aggressive periodontitis: A randomized controlled clinical trial. J Clin Periodontol 2007;34:880-91.
12Lacroix JM, Mayrand D. The effect of subminimal inhibitory concentrations of antimicrobial agents on three bacterial mixtures. Oral Microbiol Immunol 1989;4:82-8.
13Haffajee AD, Socransky SS, Dibart S, Kent RL Jr. Response to periodontal therapy in patients with high or low levels of P. gingivalis, P. intermedia, P. nigrescens and B. forsythus. J Clin Periodontol 1996;23:336-45.
14Van Winkelhoff AJ, Rodenburg JP, Goené RJ, Abbas F, Winkel EG, de Graaff J. Metronidazole plus amoxycillin in the treatment of Actinobacillus actinomycetemcomitans associated periodontitis. J Clin Periodontol 1989;16:128-31.
15Gomi K, Yashima A, Iino F, Kanazashi M, Nagano T, Shibukawa N, et al. Drug concentration in inflamed periodontal tissues after systemically administered azithromycin. J Periodontol 2007;78:918-23.
16Tamura A, Ara T, Imamura Y, Fujii T, Wang PL. The effects of antibiotics on in vitro biofilm model of periodontal disease. Eur J Med Res 2008;13:439-45.
17Blandizzi C, Malizia T, Lupetti A, Pesce D, Gabriele M, Giuca MR, et al. Periodontal tissue disposition of azithromycin in patients affected by chronic inflammatory periodontal diseases. J Periodontol 1999;70:960-6.
18Botero JE, Yepes FL, Ochoa SP, Hincapie JP, Roldan N, Ospina CA, et al. Effects of periodontal non-surgical therapy plus azithromycin on glycemic control in patients with diabetes: A randomized clinical trial. J Periodontal Res 2013;48:706-12.
19Smith SR, Foyle DM, Daniels J, Joyston-Bechal S, Smales FC, Sefton A, et al. A double-blind placebo-controlled trial of azithromycin as an adjunct to non-surgical treatment of periodontitis in adults: Clinical results. J Clin Periodontol 2002;29:54-61.
20Mascarenhas P, Gapski R, Al-Shammari K, Hill R, Soehren S, Fenno JC, et al. Clinical response of azithromycin as an adjunct to non-surgical periodontal therapy in smokers. J Periodontol 2005;76:426-36.
21Gomi K, Yashima A, Nagano T, Kanazashi M, Maeda N, Arai T. Effects of full-mouth scaling and root planing in conjunction with systemically administered azithromycin. J Periodontol 2007;78:422-9.
22Yashima A, Gomi K, Maeda N, Arai T. One-stage full-mouth versus partial-mouth scaling and root planing during the effective half-life of systemically administered azithromycin. J Periodontol 2009;80:1406-13.
23Casarin RC, Peloso Ribeiro ED, Sallum EA, Nociti FH Jr, Gonçalves RB, Casati MZ. The combination of amoxicillin and metronidazole improves clinical and microbiologic results of one-stage, full-mouth, ultrasonic debridement in aggressive periodontitis treatment. J Periodontol 2012;83:988-98.
24Xajigeorgiou C, Sakellari D, Slini T, Baka A, Konstantinidis A. Clinical and microbiological effects of different antimicrobials on generalized aggressive periodontitis. J Clin Periodontol 2006;33:254-64.
25Guerrero A, Griffiths GS, Nibali L, Suvan J, Moles DR, Laurell L, et al. 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;32:1096-107.
26Haas AN, de Castro GD, Moreno T, Susin C, Albandar JM, Oppermann RV, et al. Azithromycin as an adjunctive treatment of aggressive periodontitis: 12-months randomized clinical trial. J Clin Periodontol 2008;35:696-704.
27Mestnik MJ, Feres M, Figueiredo LC, Duarte PM, Lira EA, Faveri M. Short-term benefits of the adjunctive use of metronidazole plus amoxicillin in the microbial profile and in the clinical parameters of subjects with generalized aggressive periodontitis. J Clin Periodontol 2010;37:353-65.
28Scharf S, Wohlfeil M, Siegelin Y, Schacher B, Dannewitz B, Eickholz P. Clinical results after nonsurgical therapy in aggressive and chronic periodontitis. Clin Oral Investig 2014;18:453-60.
29Silva-Senem MX, Heller D, Varela VM, Torres MC, Feres-Filho EJ, Colombo AP. Clinical and microbiological effects of systemic antimicrobials combined to an anti-infective mechanical debridement for the management of aggressive periodontitis: A 12-month randomized controlled trial. J Clin Periodontol 2013;40:242-51.
30Arweiler NB, Pietruska M, Skurska A, Dolinska E, Pietruski JK, Bläs M, et al. Nonsurgical treatment of aggressive periodontitis with photodynamic therapy or systemic antibiotics. Three-month results of a randomized, prospective, controlled clinical study. Schweiz Monatsschr Zahnmed 2013;123:532-44.
31Ho W, Eubank T, Leblebicioglu B, Marsh C, Walters J. Azithromycin decreases crevicular fluid volume and mediator content. J Dent Res 2010;89:831-5.
32Oteo A, Herrera D, Figuero E, O'Connor A, González I, Sanz M. Azithromycin as an adjunct to scaling and root planing in the treatment of Porphyromonas gingivalis-associated periodontitis: A pilot study. J Clin Periodontol 2010;37:1005-15.
33Emingil G, Han B, Ozdemir G, Tervahartiala T, Vural C, Atilla G, et al. Effect of azithromycin, as an adjunct to nonsurgical periodontal treatment, on microbiological parameters and gingival crevicular fluid biomarkers in generalized aggressive periodontitis. J Periodontal Res 2012;47:729-39.
34Han B, Emingil G, Özdemir G, Tervahartiala T, Vural C, Atilla G, et al. Azithromycin as an adjunctive treatment of generalized severe chronic periodontitis: Clinical, microbiologic, and biochemical parameters. J Periodontol 2012;83:1480-91.