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Endocarditis Prophylaxis: Behind the Guidelines

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EDITORIAL

Dr Bernard D Prendergast DM, FRCP, Consultant, Department of Cardiology, The John Radcliffe Hospital, Oxford, UK

The evidence to support routine antibiotic prophylaxis for infective endocarditis (IE) is limited and revision of European and US guidelines has resulted in a major shift of emphasis in this contentious area.  Dramatic guidance from the UK National Institute for Health and Clinical Excellence (NICE) [1] now seems set to generate further controversy and confusion in the minds of cardiologists, dentists and their patients.

Changing epidemiology and evidence to date

The past two decades have witnessed major changes in the demography of IE, with increasing frequency of Staphylococcus aureus, often acquired as a result of nosocomial infection or intravenous drug abuse, and falling incidence of IE secondary to oral streptococci.[2]  IE often arises in patients without previously documented cardiac disease when the question of prophylaxis is irrelevant.[3]

Even if antibiotic prophylaxis is applied appropriately, the evidence to support its efficacy is limited. A recent Cochrane review concluded that there was no evidence to demonstrate whether penicillin prophylaxis is effective or ineffective in preventing IE in at risk patients undergoing an invasive dental procedure.[4]  Routine daily oral activities (e.g. tooth brushing and chewing) cause transient streptococcal bacteraemia, the cumulative result of which is an annual bacteraemic exposure thousands to millions of times greater than that caused by a single tooth extraction.[5]  Moreover, a direct link between routine dental procedures and IE has never been proven.

The only studies of the efficacy of antibiotic prophylaxis have been case-control analyses and the likelihood of a defining randomised controlled trial seems remote.  Whilst two small early studies [6,7] demonstrated that IE prophylaxis may be effective, a later two year study of 275 patients in the Netherlands concluded that most cases of IE are not attributable to an invasive procedure, but to random bacteraemia.[8]  The authors suggested that even if antibiotic prophylaxis was 100% effective then it would only prevent an extremely small number of cases of IE.  A similar French study showed that dental procedures were not associated with an increased risk of IE and that the protective efficacy of antibiotic prophylaxis was only 46% (not significant).[9]  Finally, a study conducted in 54 Philadelphian hospitals found that preceding dental treatment was no more likely in patients with IE than in controls.[10]

Even if negative, these results also fail to demonstrate that antibiotic prophylaxis of IE is ineffective.  They do, however, suggest that a huge number of prophylaxis doses are necessary to prevent a very low number of cases and that the risk of developing IE after an unprotected dental procedure is extremely low.[11]

Guidelines and philosophy

The original “treat all” philosophy was based upon an understandable fear of the condition and its complications.  However, the number needed to treat for effective prevention is exceedingly high and routine antibiotic administration is not risk free.  Anaphylaxis to ß-lactam antibiotics occurs in 15-40 per 100,000 uses (being potentially fatal in 1-3 per 100,000 uses),[12,13] and there are legitimate concerns regarding the issue of community-derived antibiotic resistance.  Thus, the cost-effectiveness of routine prophylaxis is questionable.[14]

Recently revised European and US guidelines have advocated the “number needed to treat” philosophy, restricting use of antibiotic prophylaxis to patients at the highest risk of IE undergoing the highest risk procedures (Table).[15-16,19]  The 2006 guidelines of the British Society of Antimicrobial Chemotherapy [17] also recommended prophylaxis for only those at high-risk and for whom IE would result in high mortality. Despite the absence of evidence, this publication was met with anger by the British cardiological community.[18]

However, a global shift in practice was stimulated by the 2007 American Heart Association (AHA) guidelines.[19]  These suggested prophylaxis only for those patients with high-risk cardiac disorders and indicated that prophylaxis was no longer recommended for patients with native valve disease nor for any gastrointestinal or genitourinary procedures. These guidelines seem likely to be echoed in forthcoming revised European guidance.

Finally, the most recent (and potentially most controversial) NICE guidelines espouse the “proof of principle” philosophy and suggest an end to the practice of antibiotic prophylaxis altogether.[1,20]  Whilst NICE identify patients at increased risk of developing IE, they no longer advocate prophylaxis for any dental or respiratory procedures, even for high risk groups.  However, reflecting the virulence of enterococcal IE, they recommend that at risk patients undergoing gastrointestinal or genitourinary procedures at a site where there is suspected pre-existing infection receive an antibiotic that covers IE-causative organisms.  The British Cardiovascular Society and British Heart Foundation contributed to the development of these guidelines and support their conclusions.

Concerns, questions and consensus

These varied recommendations have encountered mixed reaction – many in the dental profession, confused by previous ambiguous guidelines have praised them as “a victory for science and common sense”.[21]  On the other hand, many cardiologists maintain that they are a dangerous departure from established practice which will unnecessarily expose patients to the devastating risks of IE.[22,23]  Fear of litigation is a factor,[24] though unnecessarily so since adherence to recognised guidelines affords robust legal protection.[25]  Genuine concern for the welfare of patients is admirable, however, and careful monitoring of the incidence and presentation of IE (particularly in high risk groups) will be essential.  The means to achieve this will not be straightforward, however, and national monitoring via local databases, disease registers and conceivably the Department of Health requires exploration.  In the immediate term, unanimous interpretation and direction from the relevant professional societies (representing cardiologists, cardiothoracic surgeons, microbiologists and dental practitioners) and an open minded attitude of individual clinicians are required to stem further confusion and debate.

Disclosure

The work of Dr Prendergast is supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.  The views expressed in this publication are his and not necessarily those of the Department of Health. Dr Prendergast was an independent expert advisor to the NICE guidelines committee.  There are no other conflicts of interest.

Table: Summary of current international guidelines

References

1. NICE Short Clinical Guidelines Technical Team. Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. London: National Institute for Health and Clinical Excellence. 2008.
2. Moreillon P, Que YA. Infective endocarditis. Lancet 2004;363:139-49.
3. Hoen B. Epidemiology and antibiotic treatment of infective endocarditis: an update. Heart 2006;92:1694-700.
4. Oliver R, Roberts GJ, Hooper L. Penicillins for the prophylaxis of bacterial endocarditis in dentistry. Cochrane Database Syst Rev 2004;2:CD003813.
5. Roberts GJ. Dentists are innocent! "Everyday" bacteremia is the real culprit: a review and assessment of the evidence that dental surgical procedures are a principal cause of bacterial endocarditis in children. Pediatr Cardiol 1999;20:317-25.
6. Horstkotte D, Friedrichs W, Pippert H, et al.  Benefits of endocarditis prevention in patients with prosthetic heart valves.  Z Kardiol 1986;75:8-11.
7. Imperiale TF, Horwitz RI.  Does prophylaxis prevent postdental infective endocarditis?  A controlled evaluation of protective efficacy.  Am J Med 1990;88:131-6.
8. Van der Meer JT, Van Wijk W, Thompson J, et al. Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis. Lancet 1992;339:135-39.
9. Lacassin F, Hoen B, Leport C, et al. Procedures associated with infective endocarditis in adults. A case control study.  Eur Heart J 1995;16:1968-74.
10. Strom BL, Abrutyn E, Berlin JA, et al. Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study. Ann Intern Med 1998;129:761-69.
11. Duval X, Alla F, Hoen B, et al. Estimated risk of endocarditis in adults with predisposing cardiac conditions undergoing dental procedures with or without antibiotic prophylaxis. Clin Infect Dis 2006;42:e102-07.
12. Ahlstedt S. Penicillin allergy--can the incidence be reduced? Allergy 1984;39:151-64.
13. Lin RY.  A perspective on penicillin allergy.  Arch Intern Med 1992;152:930-37.
14. Agha Z, Lofgren RP, VanRuiswyk JV.  Is antibiotic prophylaxis for bacterial endocarditis cost-effective?  Med Decis Making 2005;25:308-20.
15. Duval X, Leport C.  Prophylaxis of infective endocarditis: current tendencies, continuing controversies.  Lancet Infect Dis 2008;8:225-32.
16. Danchin N, Duval X, Leport C. Prophylaxis of infective endocarditis: French recommendations 2002. Heart 2005;91:715-18.
17. Gould FK, Elliott TS, Foweraker J, et al. Guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2006;57:1035-42.
18. Gibbs JL, Cowie M, Brooks N. Defying explanation. Br Dent J 2006;201:188.
19. Wilson W, Taubert KA, Gewitz M, et al. 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;116:1736-54.
20. Harrison JL, Hoen B, Prendergast BD.  Antibiotic prophylaxis for infective endocarditis.  Lancet 2008;371:1317-1319.
21. Martin M. A victory for science and common sense. Br Dent J 2006; 200: 471.
22. Ashrafian H, Bogle RG.  Antimicrobial prophylaxis for endocarditis: emotion or science?  Heart 2007;93:5-6.  Responses Chalmers JA, Pullan DM Heart 2007;93:753, Ramsdale DR, Palmer ND Heart 2007;93:753.
23. Connaughton M.  Controversies in NICE guidance on infective endocarditis.  BMJ 2008;336:771.
24. Lockhart PB, Brennan MT, Fox PC, et al.  Decision-making on the use of antimicrobial prophylaxis for dental procedures: a survey of infectious diseases consultants and review.  Clin Infect Dis 2002;34:1621-26.
25. Martin MV, Longman LP, Forde MP, Butterworth ML. Infective endocarditis and dentistry: the legal basis for an association. Br Dent J 2007; 203: E1–3.

• Publication Date: 08 Sep 2008
• Publication Type: Editorial or Opinion Piece
• Creator: Dr Bernard D Prendergast DM, FRCP
• Next Review Date: 23 Aug 2010