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Inconclusive evidence on using antibiotic prophylaxis before dental procedures to prevent infective endocarditis
ORIGINAL CONTRIBUTIONS
CRITICAL SUMMARIES
Inconclusive evidence on using antibiotic prophylaxis before dental procedures to prevent infective endocarditis A critical summary of Cahill TJ, Harrison JL, Jewell P, et al. Antibiotic prophylaxis for infective endocarditis: a systematic review and meta-analysis. Heart. 2017;103(12):937-944. http://dx.doi.org/10.1136/heartjnl-2015-309102. Mohamed-Nur Abdallah, BDS, MSc, PhD
Systematic review conclusion. Despite the limited evidence and poor methodological quality of many included studies, antibiotic prophylaxis (AP) for patients at highest risk of developing infective endocarditis (IE) is a pragmatic and justified approach. However, postprocedural bacteremia may not be a good surrogate end point for IE. Critical summary assessment. This systematic review found limited evidence that was compromised by many heterogeneous studies with poor methodological quality. Based on the available evidence, no definite conclusion can be reached on the efficacy of AP in preventing IE in patients undergoing dental procedures. Evidence quality rating. Limited. Clinical question. In at-risk patients undergoing dental procedures, is the use of AP effective in preventing IE or bacteremia compared with no treatment? Review methods. Two independent reviewers searched 8 electronic databases from their inception until January or February 2016. The reviewers identified studies assessing the efficacy of AP for the prevention of IE or bacteremia in patients undergoing dental procedures but excluded studies conducted before 1960. They also excluded studies with patients undergoing cardiac surgery or implantation of cardiac electronic devices, topical therapies, and comparative antibiotic trials with no placebo or control arm. The authors used different tools depending on the type of study to assess methodological quality and risk of bias of included studies.
Their primary outcomes of interest were the incidence of any bacteremia, the incidence of IE, or for time-trend studies, the populationadjusted incidence of IE. If the total incidence of bacteremia was not reported, the authors used the highest incidence of bacteremia observed in the placebo group as a comparison. Main results. Of the 178 identified eligible articles, the authors included 36 studies comprising 21 trials, 10 time-trend studies, and 5 observational studies (4 casecontrol studies and 1 retrospective study). All included trials used bacteremia as a surrogate end point for IE. Meta-analysis of trials showed that AP is effective in reducing the incidence of bacteremia (risk ratio, 0.53 [95% confidence interval {CI}, 0.49 to 0.57; P < .01]). One timetrend study showed that total AP restriction could be associated with
an increasing incidence of IE. However, a meta-analysis of 3 case-control studies indicated no statistically significant difference in exposure to AP between test participants (patients with IE) and control participants (odds ratio ¼ 0.59 [95% CI, 0.27 to 1.30; P ¼ .14; I2¼ 48%). Conclusions. Despite the lowquality and limited available evidence, guidelines advising AP for patients at highest risk provide a pragmatic and justified approach. Postprocedural bacteremia is not a good surrogate end point for IE. Given the significant barriers to conduct randomized clinical trials (RCTs), high-quality case-control studies would help evaluate the role of dental procedures in causing IE and the efficacy of AP in its prevention. The authors did not report any sources of funding for this systematic review.
JADA
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http://jada.ada.org
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2017 1
ORIGINAL CONTRIBUTIONS
COMMENTARY Importance and context. IE is an uncommon lifethreating infection, but some patients with certain conditions or medical histories (for example, congenital heart disease or being a recipient of a prosthetic cardiac valve) have a greater risk of developing IE (high-risk patients). For decades, dental procedures have often been blamed for causing IE in at-risk patients and, thus, AP was prescribed for such patients before dental procedures to prevent IE. So far, there is no clinical evidence showing a definite link between AP and IE prevention. Recommendations from the European Society for Cardiology, American Heart Association, and American College of Cardiology advise restricting AP to patients at high risk who are undergoing high-risk dental procedures.1,2 On the other hand, the National Institute for Health and Care Excellence recommended total AP restriction in the United Kingdom.3 In 2016, under pressure from various groups, the National Institute for Health and Care Excellence softened its stance and put a qualifier into effect stating that clinicians might choose to use AP for certain high-risk patients.4 Differences between recommendations have caused much debate, and no international consensus has been reached in the dental and medical communities. Strengths and weaknesses of the systematic review. This systematic review’s authors included a comprehensive electronic search for studies that either directly or indirectly addressed the question of AP efficacy and included their references. The authors provided a well-detailed search strategy but did not clearly frame their question following the PICO model (P: patient, population, or problem; I: intervention, prognostic factor, or exposure; C: comparison or intervention; O: outcome you would like to measure or achieve) and did not follow all the guidelines suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook for systematic reviews. The authors did not report attempts to search the gray literature or hand search related journals. Inclusion was limited to Englishlanguage publications, a restriction that may have introduced bias. Descriptive tables showing both included and excluded studies were provided. The authors assessed heterogeneity between studies and their risk of bias and included tables illustrating the risk of bias assessment. The meta-analysis approach could be questioned owing to - inclusion of high-risk biased studies; - the small number of included case-control studies (3 of 5) with a relatively small sample size;
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the inability to separate the number of patients who underwent dental procedures from those who underwent other procedures in 1 included case-control study; - only studies with available data were included without reporting any attempts to retrieve missing data. Strengths and weaknesses of the evidence. The evidence identified was limited by the lack of RCTs and poor methodological quality of included studies that were heterogeneous and highly biased. The lack of randomization in the included studies may affect the internal validity. The relationship between bacteremia and IE incidence is highly questionable because poor oral hygiene, toothbrushing, and periodontal disease also induce bacteremia.5,6 Therefore, the validity of using bacteremia as a surrogate end point for IE incidence is questionable. Although 1 time-trend study indicated that total AP restriction could increase IE incidence, this type of study design is intrinsically at high risk of having methodological bias (per STRengthening the Reporting of OBservational studies in Epidemiology [STROBE] criteria) and cannot fully account for confounding factors. Meta-analysis of the case-control studies suggested a possible protective effect of AP by showing no statistically significant difference in exposure to AP between test participants (patients with IE) and control participants. However, conclusions should be drawn with caution as the detection power of the meta-analysis was limited by the small number of studies sampled, small sample size, variability between studies and poor methodological quality, and the fact that most patients in these studies were not in the high-risk category. Implications for dental practice. There is no definite conclusion about the efficacy of AP in preventing IE in patients undergoing dental procedures. Given the barriers to conducting RCTs, high-quality observational studies, particularly case-control studies, are required to address this matter as well as to decipher the relationship between IE, dental procedures, and bacteremia. Until stronger evidence is available or a new international guideline is documented, clinicians should follow the guidelines that are based on a preponderance of the best available evidence and that recommend AP for patients at high risk of developing IE before dental procedures that are known to induce bacteremia. n -
http://dx.doi.org/10.1016/j.adaj.2017.05.027 Copyright ª 2017 American Dental Association. All rights reserved.
Dr. Abdallah is a postdoctoral fellow, Faculty of Dentistry, McGill University, 2001 Avenue McGill College, Montreal, Quebec, H3A 1G1 Canada, e-mail [email protected]. Address correspondence to Dr. Abdallah.
ORIGINAL CONTRIBUTIONS
Disclosure. Dr. Abdallah did not report any disclosures. ORCID Number. Mohamed-Nur Abdallah: http://orcid.org/00000003-1179-6270. These summaries, published under the auspices of the American Dental Association Center for Evidence-Based Dentistry, are prepared by practitioners trained in critical appraisal of published systematic reviews who work under the mentorship of experts. The summaries are not intended to, and do not, express, imply, or summarize standards of care, but rather provide a concise reference for dentists to aid in understanding and applying evidence from the referenced systematic review in making clinically sound decisions as guided by their clinical judgment and by patient needs. For more information on the evidence quality rating provided above and additional critical summaries, please visit http://ebd.ada.org. 1. Habib G, Hoen B, Tornos P, et al; ESC Committee for Practice Guidelines. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30(19):2369-2413.
2. Wilson W, Taubert KA, Gewitz M, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007; 116(15):1736-1754. 3. Richey R, Wray D, Stokes T; Guideline Development Group. Prophylaxis against infective endocarditis: summary of NICE guidance. BMJ. 2008;336(7647):770-771. 4. Thornhill MH, Dayer M, Lockhart PB, et al. A change in the NICE guidelines on antibiotic prophylaxis. Br Dent J. 2016;221(3):112-114. 5. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, BahraniMougeot FK. Bacteremia associated with toothbrushing and dental extraction. Circulation. 2008;117(24):3118-3125. 6. Lockhart PB. The risk for endocarditis in dental practice. Periodontology 2000. 2000;23(1):127-135.
JADA
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http://jada.ada.org
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2017 3
CRITICAL SUMMARIES
Inconclusive evidence on using antibiotic prophylaxis before dental procedures to prevent infective endocarditis A critical summary of Cahill TJ, Harrison JL, Jewell P, et al. Antibiotic prophylaxis for infective endocarditis: a systematic review and meta-analysis. Heart. 2017;103(12):937-944. http://dx.doi.org/10.1136/heartjnl-2015-309102. Mohamed-Nur Abdallah, BDS, MSc, PhD
Systematic review conclusion. Despite the limited evidence and poor methodological quality of many included studies, antibiotic prophylaxis (AP) for patients at highest risk of developing infective endocarditis (IE) is a pragmatic and justified approach. However, postprocedural bacteremia may not be a good surrogate end point for IE. Critical summary assessment. This systematic review found limited evidence that was compromised by many heterogeneous studies with poor methodological quality. Based on the available evidence, no definite conclusion can be reached on the efficacy of AP in preventing IE in patients undergoing dental procedures. Evidence quality rating. Limited. Clinical question. In at-risk patients undergoing dental procedures, is the use of AP effective in preventing IE or bacteremia compared with no treatment? Review methods. Two independent reviewers searched 8 electronic databases from their inception until January or February 2016. The reviewers identified studies assessing the efficacy of AP for the prevention of IE or bacteremia in patients undergoing dental procedures but excluded studies conducted before 1960. They also excluded studies with patients undergoing cardiac surgery or implantation of cardiac electronic devices, topical therapies, and comparative antibiotic trials with no placebo or control arm. The authors used different tools depending on the type of study to assess methodological quality and risk of bias of included studies.
Their primary outcomes of interest were the incidence of any bacteremia, the incidence of IE, or for time-trend studies, the populationadjusted incidence of IE. If the total incidence of bacteremia was not reported, the authors used the highest incidence of bacteremia observed in the placebo group as a comparison. Main results. Of the 178 identified eligible articles, the authors included 36 studies comprising 21 trials, 10 time-trend studies, and 5 observational studies (4 casecontrol studies and 1 retrospective study). All included trials used bacteremia as a surrogate end point for IE. Meta-analysis of trials showed that AP is effective in reducing the incidence of bacteremia (risk ratio, 0.53 [95% confidence interval {CI}, 0.49 to 0.57; P < .01]). One timetrend study showed that total AP restriction could be associated with
an increasing incidence of IE. However, a meta-analysis of 3 case-control studies indicated no statistically significant difference in exposure to AP between test participants (patients with IE) and control participants (odds ratio ¼ 0.59 [95% CI, 0.27 to 1.30; P ¼ .14; I2¼ 48%). Conclusions. Despite the lowquality and limited available evidence, guidelines advising AP for patients at highest risk provide a pragmatic and justified approach. Postprocedural bacteremia is not a good surrogate end point for IE. Given the significant barriers to conduct randomized clinical trials (RCTs), high-quality case-control studies would help evaluate the role of dental procedures in causing IE and the efficacy of AP in its prevention. The authors did not report any sources of funding for this systematic review.
JADA
( )
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http://jada.ada.org
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2017 1
ORIGINAL CONTRIBUTIONS
COMMENTARY Importance and context. IE is an uncommon lifethreating infection, but some patients with certain conditions or medical histories (for example, congenital heart disease or being a recipient of a prosthetic cardiac valve) have a greater risk of developing IE (high-risk patients). For decades, dental procedures have often been blamed for causing IE in at-risk patients and, thus, AP was prescribed for such patients before dental procedures to prevent IE. So far, there is no clinical evidence showing a definite link between AP and IE prevention. Recommendations from the European Society for Cardiology, American Heart Association, and American College of Cardiology advise restricting AP to patients at high risk who are undergoing high-risk dental procedures.1,2 On the other hand, the National Institute for Health and Care Excellence recommended total AP restriction in the United Kingdom.3 In 2016, under pressure from various groups, the National Institute for Health and Care Excellence softened its stance and put a qualifier into effect stating that clinicians might choose to use AP for certain high-risk patients.4 Differences between recommendations have caused much debate, and no international consensus has been reached in the dental and medical communities. Strengths and weaknesses of the systematic review. This systematic review’s authors included a comprehensive electronic search for studies that either directly or indirectly addressed the question of AP efficacy and included their references. The authors provided a well-detailed search strategy but did not clearly frame their question following the PICO model (P: patient, population, or problem; I: intervention, prognostic factor, or exposure; C: comparison or intervention; O: outcome you would like to measure or achieve) and did not follow all the guidelines suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook for systematic reviews. The authors did not report attempts to search the gray literature or hand search related journals. Inclusion was limited to Englishlanguage publications, a restriction that may have introduced bias. Descriptive tables showing both included and excluded studies were provided. The authors assessed heterogeneity between studies and their risk of bias and included tables illustrating the risk of bias assessment. The meta-analysis approach could be questioned owing to - inclusion of high-risk biased studies; - the small number of included case-control studies (3 of 5) with a relatively small sample size;
2 JADA
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2017
the inability to separate the number of patients who underwent dental procedures from those who underwent other procedures in 1 included case-control study; - only studies with available data were included without reporting any attempts to retrieve missing data. Strengths and weaknesses of the evidence. The evidence identified was limited by the lack of RCTs and poor methodological quality of included studies that were heterogeneous and highly biased. The lack of randomization in the included studies may affect the internal validity. The relationship between bacteremia and IE incidence is highly questionable because poor oral hygiene, toothbrushing, and periodontal disease also induce bacteremia.5,6 Therefore, the validity of using bacteremia as a surrogate end point for IE incidence is questionable. Although 1 time-trend study indicated that total AP restriction could increase IE incidence, this type of study design is intrinsically at high risk of having methodological bias (per STRengthening the Reporting of OBservational studies in Epidemiology [STROBE] criteria) and cannot fully account for confounding factors. Meta-analysis of the case-control studies suggested a possible protective effect of AP by showing no statistically significant difference in exposure to AP between test participants (patients with IE) and control participants. However, conclusions should be drawn with caution as the detection power of the meta-analysis was limited by the small number of studies sampled, small sample size, variability between studies and poor methodological quality, and the fact that most patients in these studies were not in the high-risk category. Implications for dental practice. There is no definite conclusion about the efficacy of AP in preventing IE in patients undergoing dental procedures. Given the barriers to conducting RCTs, high-quality observational studies, particularly case-control studies, are required to address this matter as well as to decipher the relationship between IE, dental procedures, and bacteremia. Until stronger evidence is available or a new international guideline is documented, clinicians should follow the guidelines that are based on a preponderance of the best available evidence and that recommend AP for patients at high risk of developing IE before dental procedures that are known to induce bacteremia. n -
http://dx.doi.org/10.1016/j.adaj.2017.05.027 Copyright ª 2017 American Dental Association. All rights reserved.
Dr. Abdallah is a postdoctoral fellow, Faculty of Dentistry, McGill University, 2001 Avenue McGill College, Montreal, Quebec, H3A 1G1 Canada, e-mail [email protected]. Address correspondence to Dr. Abdallah.
ORIGINAL CONTRIBUTIONS
Disclosure. Dr. Abdallah did not report any disclosures. ORCID Number. Mohamed-Nur Abdallah: http://orcid.org/00000003-1179-6270. These summaries, published under the auspices of the American Dental Association Center for Evidence-Based Dentistry, are prepared by practitioners trained in critical appraisal of published systematic reviews who work under the mentorship of experts. The summaries are not intended to, and do not, express, imply, or summarize standards of care, but rather provide a concise reference for dentists to aid in understanding and applying evidence from the referenced systematic review in making clinically sound decisions as guided by their clinical judgment and by patient needs. For more information on the evidence quality rating provided above and additional critical summaries, please visit http://ebd.ada.org. 1. Habib G, Hoen B, Tornos P, et al; ESC Committee for Practice Guidelines. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J. 2009;30(19):2369-2413.
2. Wilson W, Taubert KA, Gewitz M, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. 2007; 116(15):1736-1754. 3. Richey R, Wray D, Stokes T; Guideline Development Group. Prophylaxis against infective endocarditis: summary of NICE guidance. BMJ. 2008;336(7647):770-771. 4. Thornhill MH, Dayer M, Lockhart PB, et al. A change in the NICE guidelines on antibiotic prophylaxis. Br Dent J. 2016;221(3):112-114. 5. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, BahraniMougeot FK. Bacteremia associated with toothbrushing and dental extraction. Circulation. 2008;117(24):3118-3125. 6. Lockhart PB. The risk for endocarditis in dental practice. Periodontology 2000. 2000;23(1):127-135.
JADA
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http://jada.ada.org
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2017 3