COMMENTARY

Hong Kong Dental Journal 2008;5:49-53

HK DJ

What every dentist needs to know about the new American and British infective endocarditis antibiotic prophylaxis guidelines
Pak-Leung Ho *, MB, BS, FACP, MRCP, FRCPA, FRCPath, FHKCPath, FHKAM (Pathology) Tak-Chiu Wu , MB, BS, MRCP, FHKCP, FHKAM (Medicine)

For decades, the American Heart Association (AHA) has made recommendations on the use of antibiotic prophylaxis for preventing infective endocarditis (IE). In April 2007, a new iteration of the guidelines was published 1. The AHA guideline writing group developed the recommendations over a 3-year period, following a search of all MEDLINE literature published from 1950 to 2006. The Infectious Diseases Society of America and the Pediatric Infectious Diseases Society have endorsed the guidelines and the guidelines relating to dentistry were subsequently approved by the American Dental Association (ADA) 2. In the UK, the British Society for Antimicrobial Chemotherapy (BSAC) also issued a new set of guidelines in 2006 3. Both guidelines approach dental prophylaxis in a similar manner, despite significant differences in their detailed recommendations (Table 1) 1,3. There are several major recommendation changes in the current AHA guidelines. Firstly, antibiotic prophylaxis is recommended only for the few cardiac conditions at very high risk of adverse outcomes from endocarditis. This change is based on the paucity of data proving that antibiotic prophylaxis before dental procedures actually prevents or reduces the risk of IE, the estimated huge level of prophylaxis required to prevent a single case of
* Department of Microbiology and Centre of Infection, The University of Hong Kong, Hong Kong Department of Medicine, Queen Elizabeth Hospital, Hospital Authority, Hong Kong Correspondence to: Dr. Pak-Leung Ho Division of Infectious Diseases, Department of Microbiology and Centre of Infection, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong Tel : (852) 2855 4897 Fax : (852) 2855 1241 e-mail : plho@hkucc.hku.hk

IE, and a lack of evidence-based method for identifying dental procedures that require prophylaxis. After a careful review of the scientific evidence, the writing group reached the consensus that it is much more likely that IE will be caused by the bacteremia associated with daily activities than that caused by a dental procedure. It has been estimated that the cumulative exposures from transient bacteremia arising from routine daily activities (e.g. tooth brushing, flossing, use of wooden toothpicks) are likely to be hundreds to thousands of times higher than that from a single dental procedure 4,5. Nonetheless, two case-control studies reported that prophylactic antibiotics reduce IE by 70% 6 and 49% 7, respectively. The annual number of IE cases associated with at-risk dental procedures has been estimated at 3.2% in France 6, 3% in the United States 8, and 5% in the Netherlands 9. Since the risk of IE occurring in patients with predisposing cardiac conditions (PCC) after at-risk dental procedures is very low, a vast amount of prophylactic antibiotics needs to be administered to prevent a small number of cases. It has been estimated that 2.7 million antibiotic courses are needed to prevent 41 and 39 cases of IE in patients with native valve PCC and prosthetic valve PCC, respectively 6. That means approximately 34 000 antibiotic courses are needed to prevent one IE case after at-risk dental procedures. Secondly, given that the estimated absolute risk rates for dental procedurerelated IE are very low in patients with particular cardiac conditions (Table 2) 10-13, both the AHA and BSAC guidelines no longer recommend prophylaxis for PCC classified as at moderate risk. Thus, the guidelines now say that prophylactic antibiotics are not needed for patients with mitral valve prolapse, rheumatic heart disease, bicuspid valve disease, calcified aortic stenosis, congenital heart diseases such as ventricular septal defects, atrial septal defects, and hypertrophic
Hong Kong Dent J Vol 5 No 1 June 2008 49

Ho and Wu

Table 1 The new American Heart Association (AHA) and British Society for Antimicrobial Chemotherapy (BSAC) guidelines on prevention of infective endocarditis (IE) * AHA guidelines High-risk cardiac conditions for which antibiotic prophylaxis is recommended 1. Prosthetic cardiac valve 2. Previous IE 3. The following CHD *: Unrepaired cyanotic CHD, including palliative shunts and conduits Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization) 4. Cardiac transplantation recipients who develop cardiac valvulopathy Dental procedure requiring antibiotic prophylaxis for the above cardiac conditions All dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa All dental procedures involving dentogingival manipulation 1. Cardiac valve replacement surgery, i.e. mechanical or biological prosthetic valves 2. Previous IE 3. Surgically constructed systemic or pulmonary shunt or conduit BSAC guidelines

* CHD denotes congenital heart disease Except for these conditions, antibiotic prophylaxis is no longer recommended for any other form of CHD The following dental procedures do not require prophylaxis: routine anesthetic injections through non-infected tissue, taking dental radiographs, placement of removable prosthodontic or orthodontic appliances, adjustment of orthodontic appliances, placement of orthodontic brackets, shedding of deciduous teeth, and bleeding from trauma to the lips or oral mucosa

Table 2 Risk estimates for infective endocarditis (IE) 10-13 Incidence of IE (per 100 000 patient-years) Reference General population Mitral valve prolapse Congenital heart disease Rheumatic heart disease Native valve PCC Previous IE Valvular replacement for native valve endocarditis Valvular replacement for prosthetic valve endocarditis

Estimated absolute IE risk resulting from a dental procedure (per number of procedures) Pallasch 11 1 in 14 000 000 1 in 1 100 000 1 in 475 000 1 in 142 000 1 in 114 000 1 in 95 000 Duval and Leport 12 1 in 54 300 1 in 10 700 -

Steckelberg and Wilson 10 5 4.6-52 145-271* 380-440 308-383 740 630 2160

Prosthetic heart valve

* Estimates for congenital aortic stenosis and ventricular septic defect 13 PCC denotes predisposing cardiac conditions

cardiomyopathy. Since these changed recommendations represent a broad consensus among the working groups rather than hard scientific evidence, several groups have expressed disagreement 14-16. For this reason, the ADA recommends that dentists use their independent professional judgment when applying the AHA or any other appropriate guidelines in any clinical situation. Patients may present with a recommendation from a
50 Hong Kong Dent J Vol 5 No 1 June 2008

treating physician with which the dentist disagrees. If the treating physician and dentist cannot reach a consensus on treatment, the answer may lie with informed consent 17. As part of good clinical practice, the dentist should carefully record all communications regarding treatment options. In a review of 83 IE legal cases which successfully established a link with dental treatment, most of the clinicians involved had failed to follow recognized

Antibiotic prophylaxis of infective endocarditis

Table 3 Antibiotic prophylaxis regimens for dental procedures * Situation Oral General Allergic to penicillins or ampicillin Amoxicillin Clindamycin Azithromycin Clarithromycin Cephalexin Unable to take oral medication General Ampicillin Cefazolin Allergic to penicillins or ampicillin Ceftriaxone Clindamycin Cefazolin

Agent

AHA guidelines Adults 2 g 600 mg 500 mg 500 mg 2 g 2g iv or im 1g iv or im 1g iv or im 600 mg iv or im 1g iv or im 1g iv or im Children 50 mg/kg 20 mg/kg 15 mg/kg 15 mg/kg 50 mg/kg 50 mg/kg iv or im 50 mg/kg iv or im 50 mg/kg iv or im 20 mg/kg iv or im 50 mg/kg iv or im 50 mg/kg iv or im 10 years 3 g 600 mg 500 mg 1g iv II 300 mg iv -

BSAC guidelines 5 to <10 years 1.5 g 300 mg 300 mg 500 mg iv II 150 mg iv <5 years 750 mg 150 mg 200 mg 250 mg iv II 75 mg iv -

Ceftriaxone

* AHA denotes American Heart Association, BSAC British Society for Antimicrobial Chemotherapy, iv intravenous, and im intramuscular Single dose 30 minutes to 1 hour before the procedure Single dose 1 hour before the procedure for an oral regimen and just before the procedure or at the induction of anesthesia for intravenous regimens Because of possible cross-reactions, cephalosporins should not be used in an individual with a history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin II Amoxicillin was recommended

guidelines or to keep adequate clinical notes 18. The dental procedures associated with such cases included scaling (n=29), exodontia (n=28), endodontics (n=12), and minor oral surgery (n=11). In all the cases, either no antibiotic prophylaxis was given or non-recommended antibiotics were used. Although the cases were judged before publication of the new guidelines, it is important to note that only one patient was considered to be at high risk. The 83 cases had coarctation of the aorta (n=54), mitral valve disease (n=16), a history of a murmur (n=11), a history of rheumatic fever (n=1), and previous IE (n=1). It has also been argued that a distinction should be made between total bacteremia and streptococcal bacteremia because it is the latter which has been associated with IE 16,19. The existing data show that streptococcal bacteremia rates are higher after extractions than endodontic treatment, chewing, and toothbrushing 16. In addition, it has been shown that post-extraction streptococcal bacteremia persists for at least 1 hour in as many as 20% of individuals, independently of their grade of oral health 20. Hence, until more data able to definitively

inform a change of practice are available, it may be reasonable to continue antibiotic cover for patients with moderate-risk heart lesions undergoing dental extractions or oral surgery 16. Streptococcal endocarditis has a mortality rate of about 10% 1. From this mortality rate and the one in 54 300 unprotected procedural risk of IE, the risk of death from IE during unprotected procedures can be estimated at approximately two per million 12. This risk is lower than that of fatal anaphylactic reactions to penicillin, which ranges from 15 to 25 per million doses of penicillin 21,22. Nevertheless, it is possible that a single dose of oral amoxicillin is less likely to cause fatal anaphylaxis. As noted by the AHA guidelines, there have been no reports of fatal anaphylaxis resulting from the use of amoxicillin for IE prophylaxis in the last 50 years. Changes have also been made to the antibiotic prophylaxis regimens recommended for dental procedures but the AHA and BSAC guidelines continue to diverge on details such as dosage and alternatives to amoxicillin for patients with histories of allergy (Table 3). The AHA
Hong Kong Dent J Vol 5 No 1 June 2008 51

Ho and Wu

Table 4 Recommendations on maintenance of dental care and oral hygiene * AHA guidelines 1. There should be a change in emphasis from antibiotic prophylaxis towards improved access to dental care and oral health in patients with PCC BSAC guidelines 1. Access to high-quality dental care should be facilitated in susceptible individuals

2. Once a patient is diagnosed to have a PCC, the patient should be referred to have their dental hygiene optimized 2. For patients scheduled for dental or other treatment, alert to the possibility of coincidental IE when patient has fever or 3. A patient who has received an intracardiac prosthesis (e.g. other manifestations of systemic infection valve, conduit, and aortic graft) should be referred for dental assessment 3. A careful preoperative dental evaluation is recommended before cardiac valve surgery, replacement or repair of 4. Dental interventions ideally should be performed at least 14 congenital heart disease days prior to cardiac surgery to allow mucosal healing 5. Patients who have emergency valve replacement should have a dental assessment as soon as practicable after surgery, and a risk assessment performed to determine the most appropriate plan for remedial dental treatment

* AHA denotes American Heart Association, BSAC British Society for Antimicrobial Chemotherapy, PCC predisposing cardiac conditions, and IE infective endocarditis

guidelines continue to recommend cephalosporins and clarithromycin as potential alternatives to amoxicillin 1,23 but the BSAC guidelines make no recommendation on the use of these agents 3. A recent literature review concluded that amoxicillin is highly effective for preventing bacteremia following dental procedures but that the efficacy of other recommended antibiotics remains unconfirmed 24. The two guidelines also differ on the utility of antiseptic mouthwash before dental procedures. The BSAC guidelines recommend a preoperative mouthwash with 0.2% chlorhexidine gluconate and say that this should be held in the mouth for 1 minute, but the AHA guidelines consider such use controversial. In a recent randomized controlled trial, preoperative use of 0.2% chlorhexidine mouthwash reduced the prevalence of bacteremia after dental extraction from 64% to 30% at 15 minutes, and from 20% to 2% at 1 hour 25. Since the present guidelines are largely consensusbased, several aspects continue to be controversial. In both, the focus is on limiting prophylaxis to the procedures and the populations at highest risk. So far, the new guidelines seem to have generated more confusion and problems for practicing dentists than solutions. In the UK, the latest guidelines from the National Institute for Health and Clinical Excellence (NICE) group is the most radical in that it recommends abandoning prophylactic antibiotics and chlorhexidine mouthwashes for patients at risk because there is insufficient evidence that they reduce IE 26,27 . In the NICE guidelines, antibiotic prophylaxis against IE is not recommended for patients undergoing dental procedures, even those traditionally
52 Hong Kong Dent J Vol 5 No 1 June 2008

considered to be at high risk. Not surprisingly, there was immediate criticism 28. The ADAs legal position is that when treatment consensus among treating professionals is absent, it is prudent also to disclose that the treatment recommendations differ and to encourage the patient to discuss treatment options with the physician before making a decision regarding treatment 17. Since the presence of dental disease and cumulative bacteremia from daily activities may pose a greater risk of IE, it is now time for greater emphasis on improved access to dental care and oral health in patients with PCC (Table 4). Indeed, this is the only consensus in all the new guidelines on prophylaxis against IE.

References
1. 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. Erratum in: Circulation 2007;116:e376-7. 2. 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. J Am Dent Assoc 2008;139 Suppl:S3-24. Erratum in: J Am Dent Assoc 2008;139:253. 3. Gould FK, Elliott TS, Foweraker J, et al. Guidelines for the prevention of endocarditis: report of the Working Party of the

Antibiotic prophylaxis of infective endocarditis

British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2006;57:1035-42. 4. Guntheroth WG. How important are dental procedures as a cause of infective endocarditis? Am J Cardiol 1984;54:797-801. 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. 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:e102-7. 7. Van der Meer JT, Van Wijk W, Thompson J, Vandenbroucke JP, Valkenburg HA, Michel MF. Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis. Lancet 1992;339:135-9. 8. 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;129:761-9. 9. van der Meer JT, Thompson J, Valkenburg HA, Michel MF. Epidemiology of bacterial endocarditis in The Netherlands. II. Antecedent procedures and use of prophylaxis. Arch Intern Med 1992;152:1869-73. 10. Steckelberg JM, Wilson WR. Risk factors for infective endocarditis. Infect Dis Clin North Am 1993;7:9-19. 11. Pallasch TJ. Antibiotic prophylaxis: problems in paradise. Dent Clin North Am 2003;47:665-79. 12. Duval X, Leport C. Prophylaxis of infective endocarditis: current tendencies, continuing controversies. Lancet Infect Dis 2008;8:22532. 13. Gersony WM, Hayes CJ, Driscoll DJ, et al. Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation 1993;87(2 Suppl):I121-6. 14. Gibbs JL, Cowie M, Brooks N. Comment on: guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2006;58:896-8. 15. Ramsdale DR, Morrison L, Palmer MD, Fabri B. Lethal consequences. Br Dent J 2006;201:187. 16. Shanson D. New British and American guidelines for the antibiotic

prophylaxis of infective endocarditis: do the changes make sense? A critical review. Curr Opin Infect Dis 2008;21:191-9. 17. American Dental Association Division of legal affairs. An updated legal perspective on antibiotic prophylaxis: American Dental Association Division of Legal Affairs. J Am Dent Assoc 2008;139 Suppl:S10. 18. Martin MV, Longman LP, Forde MP, Butterworth ML. Infective endocarditis and dentistry: the legal basis for an association. Br Dent J 2007;203:E1. 19. Shanson D. Comment on: guidelines for the prevention of endocarditis: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J Antimicrob Chemother 2006;58:895. 20. Toms I, Alvarez M, Limeres J, Potel C, Medina J, Diz P. Prevalence, duration and aetiology of bacteraemia following dental extractions. Oral Dis 2007;13:56-62. 21. Ahlstedt S. Penicillin allergycan the incidence be reduced? Allergy 1984;39:151-64. 22. Idsoe O, Guthe T, Willcox RR, de Weck AL. Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock. Bull World Health Organ 1968;38:15988. 23. Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis: recommendations by the American Heart Association. Clin Infect Dis 1997;25:1448-58. 24. Toms Carmona I, Diz Dios P, Scully C. Efficacy of antibiotic prophylactic regimens for the prevention of bacterial endocarditis of oral origin. J Dent Res 2007;86:1142-59. 25. Toms I, Alvarez M, Limeres J, et al. Effect of a chlorhexidine mouthwash on the risk of postextraction bacteremia. Infect Control Hosp Epidemiol 2007;28:577-82. 26. National Institute for Health and Clinical Excellence. Prophylaxis against infective endocarditis. NICE Clinical Guideline No. 64 2008. NICE website: http://www.nice.org.uk/. Accessed April 20, 2008. 27. Richey R, Wray D, Stokes T; Guideline Development Group. Prophylaxis against infective endocarditis: summary of NICE guidance. BMJ 2008;336:770-1. 28. Connaughton M. Commentary: Controversies in NICE guidance on infective endocarditis. BMJ 2008;336:771.

Hong Kong Dent J Vol 5 No 1 June 2008

53