Letters to the Editor
75. Johnson JD, Chen R, Lenton PA, Zhang G, Hinrichs JE, Rudney JD. Persistence of extracrevicular bacterial reservoirs after treatment of aggressive periodontitis. J Periodontol 2008;79:2305-2312. 76. Machtei EE, Younis MN. The use of 2 antibiotic regimens in aggressive periodontitis: Comparison of changes in clinical parameters and gingival crevicular fluid biomarkers. Quintessence Int 2008;39:811-819. 77. Kaner D, Christian C, Dietrich T, Bernimoulin J-P, Kleber B-M, Friedman A. Timing affects the clinical outcome of adjunctive systemic antibiotic therapy for generalized aggressive periodontitis. J Periodontol 2007;78:1201-1208. 78. Moeintaghavi A, Talebi-ardakani MR, Haerian-ardakani A, et al. Adjunctive effects of systemic amoxicillin and metronidazole with scaling and root planing: A randomized, placebo-controlled clinical trial. J Contemp Dent Pract 2007;8:51-59. 79. Moreira RM, Feres-Filho EJ. Comparison between fullmouth scaling and root planing and quadrant-wise basic therapy of aggressive periodontitis. Six-month clinical results. J Periodontol 2007;78:1683-1688. 80. Guerrero A, Echeverria JJ, Tonetti MS. Incomplete adherence to an adjunctive systemic antibiotic regimen decreases clinical outcomes in generalized aggressive periodontitis patients: A pilot retrospective study. J Clin Periodontol 2007;34:897-902. 81. Ehmke B, Beikler T, Haubitz I, Karch H, Flemmig TF. Multifactorial assessment of predictors for prevention of periodontal disease progression. Clin Oral Investig 2003;7:217-221. Submitted June 13, 2013; accepted for publication June 13, 2013. doi: 10.1902/jop.2014.130379
Authors’ Response (Zandbergen et al.): Since the introduction of combined antibiotic therapy in the 1990s, periodontists have noticed that supporting initial treatment with this medication may enhance the treatment effect and subsequently reduce the need for periodontal surgery. This practicebased observation has initiated a large number of studies throughout the world. More than 10 years ago, two systematic reviews were published by Herrera et al.1 and Haffajee et al.2 on the topic of antibiotics in combination with initial therapy. Since then, more papers have become available. Therefore, we decided to update the evidence-based knowledge, specifically focusing on metronidazole and amoxicillin. Based on a comprehensive search of the literature and predefined eligibility criteria, we critically appraised the selected papers on heterogeneity and quality in order to assess the risk of bias. In conclusion, we specifically stated that systemic antimicrobial therapy, using a combination of amoxicillin and metronidazole as an adjunct to scaling and root planing, can enhance the clinical benefits of non-surgical periodontal therapy in adults who are otherwise healthy. 384
Volume 85 • Number 3
In the letter to the editor, four general issues were addressed as potential caveats: 1. Heterogeneity — Heterogeneity in meta-analysis is a consequence of clinical or methodological diversity or both among studies and is to be expected. Statistical heterogeneity suggests that the studies are not all estimating the same quantity, and it would be surprising if multiple studies, performed by different teams in different places with different methods, all ended up estimating the same underlying parameter. On the other hand, the heterogeneity observed most likely reflects what the dental care professional encounters in his/her practice population. Rarely do two patients present with identical disease in terms of severity, rate of progression, and clinical presentation. The results presented in our review give guidance in what may be expected clinically when treating the ‘‘average’’ private practice patient. 2. Short follow-up — In our systematic review, we took the outcome of the longest follow-up. Indeed, some studies had limited study duration of 2 months; however, we do not understand the comment that the clinical outcome measurement of these studies is not of interest. In daily periodontal practice, the reevaluation of initial therapy is conducted somewhere between 2 to 4 months at which time the decision is made regarding the next step in treatment, i.e., retreatment, surgery, or assignment to periodontal maintenance. We disagree with the suggestion that small sample studies are a concern. When a weighted mean is calculated, the sample size is taken into account, and the purpose of a meta-analysis is exactly that small studies (sometimes even underpowered) are combined into one overall test. This is the power of a systematic review. 3. Criteria for selecting antibiotics — Indeed, over the last 2 decades, decisions to use antibiotics adjunctive to scaling and root planing have been, for the most part, based on microbiological data. However, analyzing a biofilm by specifically looking at a single species has been questioned in light of the latest microbiological techniques. The diversity of the oral microbiome is far more complex than we originally realized. Subsequently, criteria for the adjunctive use of antibiotics may better be defined based on clinical criteria until more modern microbiological criteria are defined. The outcome of our review indicates that the severity of the disease (as assessed by probing depth) could be selected as one such criterion. 4. Overall clinical strategy — Although we could not find the related paragraph for this in our published article, we indeed share the concerns regarding misuse of antibiotics and appreciate the detailed additional review of the selected studies. In our paper, we expressed our concern regarding the potential abuse of antimicrobial treatments by their use in the absence of thorough subgingival debridement. Obviously, such an
Letters to the Editor
J Periodontol • March 2014
approach may contribute to the worldwide increase of bacterial resistance to antibiotics. We also realize that many medical doctors prescribe antibiotics to patients for other diseases without checking the periodontal condition. Given the prevalence of periodontal diseases, this should be considered with trepidation in light of the concern raised by Preus and colleagues. Rams et al.3 have shown that patients with chronic periodontitis yielded subgingival periodontal pathogens resistant in vitro to therapeutic concentrations of antibiotics commonly used in clinical periodontal practice. However, in case the dental professional decides for antibiotic support, clinical periodontitis treatment strategies involving the combination of systemic amoxicillin plus metronidazole should be considered.4 This combination also appears relevant in peri-implantitis patients.5 General Comment Evidence-based decision making is based on four pillars, i.e., the available scientific evidence, the practitioner’s experience, patient preference, and available materials/products/procedures. Based on each individual evidence-based decision, the pillars are integrated in the decision but the weight of these four pillars may vary. With our systematic review, we have provided just one piece of the puzzle. The other aspects should be considered by the dental care professional before he/she decides to prescribe adjunctive antibiotics as a component of initial periodontal therapy. Dina Zandbergen, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands and Clinic for Periodontology, Utrecht, The Netherlands;
Dagmar E. Slot, ACTA, University of Amsterdam and VU University; Charles M. Cobb, Department of Periodontics, School of Dentistry, University of Missouri–Kansas City, Kansas City, MO; and Fridus A. Van der Weijden, ACTA, University of Amsterdam and VU University, and Clinic for Periodontology. The authors report no conflicts of interest related to this letter. REFERENCES 1. Herrera D, Sanz M, Jepsen S, Needleman I, Rolda´n S. A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol 2002;29:136-159. 2. Haffajee AD, Socransky SS, Gunsolley JC. Systemic anti-infective periodontal therapy. A systematic review. Ann Periodontol 2003;8:115-181. 3. Rams TE, Degener JE, van Winkelhoff AJ. Antibiotic resistance in human chronic periodontitis microbiota. J Periodontol 2014;85:160-169. 4. Rams TE, Degener JE, van Winkelhoff AJ. Prevalence of b-lactamase–producing bacteria in human periodontitis. J Periodontal Res 2013;48:493-499. 5. Rams TE, Degener JE, van Winkelhoff AJ. Antibiotic resistance in human peri-implantitis microbiota. Clin Oral Implants Res 2014;25:82-90. Submitted July 8, 2013; accepted for publication July 8, 2013. doi: 10.1902/jop.2014.130436
Authors’ Response (Sgolastra et al.): The authors chose not to respond.
385
75. Johnson JD, Chen R, Lenton PA, Zhang G, Hinrichs JE, Rudney JD. Persistence of extracrevicular bacterial reservoirs after treatment of aggressive periodontitis. J Periodontol 2008;79:2305-2312. 76. Machtei EE, Younis MN. The use of 2 antibiotic regimens in aggressive periodontitis: Comparison of changes in clinical parameters and gingival crevicular fluid biomarkers. Quintessence Int 2008;39:811-819. 77. Kaner D, Christian C, Dietrich T, Bernimoulin J-P, Kleber B-M, Friedman A. Timing affects the clinical outcome of adjunctive systemic antibiotic therapy for generalized aggressive periodontitis. J Periodontol 2007;78:1201-1208. 78. Moeintaghavi A, Talebi-ardakani MR, Haerian-ardakani A, et al. Adjunctive effects of systemic amoxicillin and metronidazole with scaling and root planing: A randomized, placebo-controlled clinical trial. J Contemp Dent Pract 2007;8:51-59. 79. Moreira RM, Feres-Filho EJ. Comparison between fullmouth scaling and root planing and quadrant-wise basic therapy of aggressive periodontitis. Six-month clinical results. J Periodontol 2007;78:1683-1688. 80. Guerrero A, Echeverria JJ, Tonetti MS. Incomplete adherence to an adjunctive systemic antibiotic regimen decreases clinical outcomes in generalized aggressive periodontitis patients: A pilot retrospective study. J Clin Periodontol 2007;34:897-902. 81. Ehmke B, Beikler T, Haubitz I, Karch H, Flemmig TF. Multifactorial assessment of predictors for prevention of periodontal disease progression. Clin Oral Investig 2003;7:217-221. Submitted June 13, 2013; accepted for publication June 13, 2013. doi: 10.1902/jop.2014.130379
Authors’ Response (Zandbergen et al.): Since the introduction of combined antibiotic therapy in the 1990s, periodontists have noticed that supporting initial treatment with this medication may enhance the treatment effect and subsequently reduce the need for periodontal surgery. This practicebased observation has initiated a large number of studies throughout the world. More than 10 years ago, two systematic reviews were published by Herrera et al.1 and Haffajee et al.2 on the topic of antibiotics in combination with initial therapy. Since then, more papers have become available. Therefore, we decided to update the evidence-based knowledge, specifically focusing on metronidazole and amoxicillin. Based on a comprehensive search of the literature and predefined eligibility criteria, we critically appraised the selected papers on heterogeneity and quality in order to assess the risk of bias. In conclusion, we specifically stated that systemic antimicrobial therapy, using a combination of amoxicillin and metronidazole as an adjunct to scaling and root planing, can enhance the clinical benefits of non-surgical periodontal therapy in adults who are otherwise healthy. 384
Volume 85 • Number 3
In the letter to the editor, four general issues were addressed as potential caveats: 1. Heterogeneity — Heterogeneity in meta-analysis is a consequence of clinical or methodological diversity or both among studies and is to be expected. Statistical heterogeneity suggests that the studies are not all estimating the same quantity, and it would be surprising if multiple studies, performed by different teams in different places with different methods, all ended up estimating the same underlying parameter. On the other hand, the heterogeneity observed most likely reflects what the dental care professional encounters in his/her practice population. Rarely do two patients present with identical disease in terms of severity, rate of progression, and clinical presentation. The results presented in our review give guidance in what may be expected clinically when treating the ‘‘average’’ private practice patient. 2. Short follow-up — In our systematic review, we took the outcome of the longest follow-up. Indeed, some studies had limited study duration of 2 months; however, we do not understand the comment that the clinical outcome measurement of these studies is not of interest. In daily periodontal practice, the reevaluation of initial therapy is conducted somewhere between 2 to 4 months at which time the decision is made regarding the next step in treatment, i.e., retreatment, surgery, or assignment to periodontal maintenance. We disagree with the suggestion that small sample studies are a concern. When a weighted mean is calculated, the sample size is taken into account, and the purpose of a meta-analysis is exactly that small studies (sometimes even underpowered) are combined into one overall test. This is the power of a systematic review. 3. Criteria for selecting antibiotics — Indeed, over the last 2 decades, decisions to use antibiotics adjunctive to scaling and root planing have been, for the most part, based on microbiological data. However, analyzing a biofilm by specifically looking at a single species has been questioned in light of the latest microbiological techniques. The diversity of the oral microbiome is far more complex than we originally realized. Subsequently, criteria for the adjunctive use of antibiotics may better be defined based on clinical criteria until more modern microbiological criteria are defined. The outcome of our review indicates that the severity of the disease (as assessed by probing depth) could be selected as one such criterion. 4. Overall clinical strategy — Although we could not find the related paragraph for this in our published article, we indeed share the concerns regarding misuse of antibiotics and appreciate the detailed additional review of the selected studies. In our paper, we expressed our concern regarding the potential abuse of antimicrobial treatments by their use in the absence of thorough subgingival debridement. Obviously, such an
Letters to the Editor
J Periodontol • March 2014
approach may contribute to the worldwide increase of bacterial resistance to antibiotics. We also realize that many medical doctors prescribe antibiotics to patients for other diseases without checking the periodontal condition. Given the prevalence of periodontal diseases, this should be considered with trepidation in light of the concern raised by Preus and colleagues. Rams et al.3 have shown that patients with chronic periodontitis yielded subgingival periodontal pathogens resistant in vitro to therapeutic concentrations of antibiotics commonly used in clinical periodontal practice. However, in case the dental professional decides for antibiotic support, clinical periodontitis treatment strategies involving the combination of systemic amoxicillin plus metronidazole should be considered.4 This combination also appears relevant in peri-implantitis patients.5 General Comment Evidence-based decision making is based on four pillars, i.e., the available scientific evidence, the practitioner’s experience, patient preference, and available materials/products/procedures. Based on each individual evidence-based decision, the pillars are integrated in the decision but the weight of these four pillars may vary. With our systematic review, we have provided just one piece of the puzzle. The other aspects should be considered by the dental care professional before he/she decides to prescribe adjunctive antibiotics as a component of initial periodontal therapy. Dina Zandbergen, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands and Clinic for Periodontology, Utrecht, The Netherlands;
Dagmar E. Slot, ACTA, University of Amsterdam and VU University; Charles M. Cobb, Department of Periodontics, School of Dentistry, University of Missouri–Kansas City, Kansas City, MO; and Fridus A. Van der Weijden, ACTA, University of Amsterdam and VU University, and Clinic for Periodontology. The authors report no conflicts of interest related to this letter. REFERENCES 1. Herrera D, Sanz M, Jepsen S, Needleman I, Rolda´n S. A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol 2002;29:136-159. 2. Haffajee AD, Socransky SS, Gunsolley JC. Systemic anti-infective periodontal therapy. A systematic review. Ann Periodontol 2003;8:115-181. 3. Rams TE, Degener JE, van Winkelhoff AJ. Antibiotic resistance in human chronic periodontitis microbiota. J Periodontol 2014;85:160-169. 4. Rams TE, Degener JE, van Winkelhoff AJ. Prevalence of b-lactamase–producing bacteria in human periodontitis. J Periodontal Res 2013;48:493-499. 5. Rams TE, Degener JE, van Winkelhoff AJ. Antibiotic resistance in human peri-implantitis microbiota. Clin Oral Implants Res 2014;25:82-90. Submitted July 8, 2013; accepted for publication July 8, 2013. doi: 10.1902/jop.2014.130436
Authors’ Response (Sgolastra et al.): The authors chose not to respond.
385
