Antibiotic prophylaxis of endocarditis:
the rest of the world and NICE
John B Chambers1, David Shanson2, Roger Hall3, John Pepper4, Graham Venn1
On behalf of the British Valve Group
1 Cardiothoracic Centre, Guy’s and St Thomas’ Hospitals, London, UK
3 Department of Cardiology, University of East Anglia, UK
2 Department of Medical Microbiology, Great Ormond Street
4 Cardiac Surgery, Royal Brompton Hospital, London, UK
Previous guidelines1,2 recommended antibiotic prophylaxis
an inconsistent relationship between bacterial load and the
for the majority of patients with congenital and heart valve
likelihood of IE depending on the strain of alpha-haemolytic
disease. Almost all current national or international guide-
streptococcus. There may also be genetic differences in
lines including those from the USA3,4, Europe5, and
susceptibility16. These possibilities may help to explain vari-
Australia6,7, have narrowed these recommendations radical-
ly, but still recommend prophylaxis for certain dental proce-dures in high risk cardiac patients (Table 1). NICE8 is alone
The NICE committee correctly stated that, in the absence of
in recommending no antibiotic prophylaxis for any cardiac
a prospective randomised clinical trial, the clinical effective-
patients undergoing dental or non-dental procedures
ness of antibiotic prophylaxis is not proven. However a
except for manipulations at an infected non-dental site.
number of studies suggest a benefit. A Dutch case-con-
Most cardiologists and cardiac surgeons still follow
trolled study13, which was also the only study found eligible
International guidelines rather than NICE. Is this justified?
for a Cochrane review17, suggested a reduction in risk ofonly 49%. This was based on 48 cases with endocarditis
The NICE committee8 based their advice on the
after a dental or non-dental procedure, but, importantly,
excluded high-risk patients with prosthetic valves. In astudy specifically of prosthetic valves12 there were 6 cases
(1) there is no consistent association between having an
of IE in 304 who were unprotected by antibiotics, but no
interventional procedure, dental or non-dental, and the
cases in 229 protected patients. A French study18 estimated
development of infective endocarditis (IE). Regular
an incidence of IE in patients with valve disease of 1 case
toothbrushing almost certainly represents a greater risk
per 46,000 unprotected dental procedures compared with
1 case per 149,000 protected procedures. The protectiveeffect of antibiotics has been estimated at 46%11, 49%13,
(2) the clinical effectiveness of antibiotic prophylaxis is not
70%18 and 91%19. These clinical observations suggests
that animal work showing the effectiveness of a single doseof amoxicillin in preventing streptococcal endocarditis20,21
(3) antibiotic prophylaxis for dental procedures may lead
to a greater number of deaths through fatal anaphylaxisthan a strategy of no antibiotic prophylaxis and is not
The NICE8 committee considered, but decided against,
defining a high risk group, to include patients with pros-thetic valves, because it felt that this would be confusing.
Although NICE dismissed an association between a dental
Patients with prosthetic valves have a 5-fold higher risk of
procedure and the development of endocarditis, many of
developing IE than those with native valve disease17. The
the studies cited (para 2.3.2) suggest a link. A case-
mortality is substantially higher, about 25% during the
matched study9 of 273 patients with IE found no associa-
acute event22, and up to 41% at 30 days23. Long-term sur-
tion with dental work in general, but extractions occurred
vival rates are only 55% at 5 years and 38% at 10 years24.
in 6 patients with IE and in no case-controls (p= 0.03).
This is largely because 10-35% of survivors need further
However, only about a third had IE as a result of mouth
cardiac surgery which is at markedly increased risk24,25.
organisms and the extractions were not performed in
International guideline groups3-7, clinical studies11,18 and a
patients with valve disease. A Dutch study showed that a
study modelling cost-effectiveness26 conclude, differently
combination of a heart lesion, natural dentition and a den-
from NICE, that antibiotic prophylaxis, while no longer
tal procedure gave a relative risk for IE of 4.910. A French
generally advisable, should be focused on such high-risk
case-controlled study11 showed a significant association
between IE and repeated scaling and canal treatmentalthough not for all dentistry. Other studies12-14 have also
The NICE committee quoted a risk of fatal anaphylaxis of
found an association between IE and extraction or, less
approximately 20 per million administrations of penicillin.
frequently, with root canal work. Animal models15 suggest
This figure is based mainly on data published in the 1960s
few patients at high risk of endocarditis (Table 1) compared
when most of the subjects dying received parenteral
to those with native valve disease. The cost saved by
penicillin27, often to treat syphilis. There is little published
adopting the NICE guidelines would therefore be relatively
information on the risks of oral amoxicillin, but yellow card
small. We suspect it would be offset by unnecessary deaths
returns in the UK suggest that fatal anaphylaxis is extremely
since there is good reason to think that antibiotic prophy-
rare and the figures quoted by NICE may be an over esti-
laxis may be effective in high-risk groups before high risk
mate28. In the world literature there have been no reports
of fatal anaphylaxis after oral amoxicillin prophylaxis forendocarditis. Patients with prosthetic valves who have
There is no national surveillance programme for endocarditis
received amoxicillin prophylaxis in the past without any
to alert us to any potential increase in the incidence of
problems are unlikely to develop anaphylaxis. Testing for
prosthetic endocarditis as a result of the NICE guidelines.
In our current state of knowledge, International guidelinesthat continue to recommend antibiotic prophylaxis for high
All guidelines agree that the main measure for preventing
risk cardiac patients, particularly those with prosthetic
IE is the maintenance of excellent oral hygiene. There are
heart valves, remain preferable to NICE.
14. Starkbaum M, Durack D, Beeson P. The incubation period of subacute
1. Dajani AS, Taubert KA, Wilson W et al. Prevention of bacterial endocardi-
bacterial endocarditis. Yale J Biol Med
1977; 50: 49–58.
tis. Recommendations of the American Heart Association. Circulation
1997; 96: 358–66.
15. Malinverni R, Glauser MP. The value of experimental models in the pro-
phylaxis of bacterial endocarditis. Europ Heart J
1987; 8 (Suppl J): 357-9.
2. Working Party of the British Society for Antimicrobial Chemotherapy,
Antibiotic Prophylaxis of Infective Endocarditis. Lancet
1990; 335: 88–89.
16. Duval X, Leport C. Prophylaxis of infective endocarditis: current tenden-
cies, continuing controversies. Lancet Infect Dis
3. Wilson W, Taubert KA, Gewitz M et al. Prevention of infective endocardi-
tis. Guidelines from the American Heart Association, Rheumatic Fever,
17. Oliver R, Roberts GJ, Hooper L, Worthington HV. Antibiotics for the pro-
Endocarditis, and Kawasaki Disease Committee, Council on
phylaxis of bacterial endocarditis in dentistry (Review). The Cochrane
Cardiovascular Disease in the Young, and the Council on Clinical
Cardiology, Council on Cardiovascular Surgery and Anaesthesia, and the
18. Duval X, Alla F, Hoen B et al. Estimated risk of endocarditis in adults with
Quality of Care and Outcomes Research Interdisciplinary Working Group.
predisposing cardiac conditions undergoing dental procedures with or
2007; 116: 1736–54.
without antibiotic prophylaxis. Clin Infectious Dis
2006; 42: e102-7.
4. Nishimura RA, Carabello BA, Faxon DP et al. ACC/AHA guideline update
19. Imperiale TF, Horwitz RI. Does prophylaxis prevent postdental infective
on valvular heart disease: focused update on infective endocarditis.
endocarditis? A controlled evaluation of protective efficacy. Am J Med
2008; 118: 887-96.
5. Habib G, Hoen B, Tornos P et al. Guidelines on the prevention, diagnosis,
20. Glauser M, Bernard J, Moreillon P et al. Succesful single–dose amoxycillin
and treatment of infective endocarditis (new version 2009). The Task
prophylaxis against experimental streptococcal endocarditis: evidence
Force on the Prevention , Diagnosis and Treatment of Infective
for two mechanisms of protection. J Infect Dis
1983; 147: 568–75.
Endocarditis of the European Society of Cardiology. European Heart J
21. Berney P, Francioli P. Successful prophylaxis of experimental streptococcal
endoacarditis with single-dose amoxicillin administered after bacterial
6. Infective Endocarditis Prophylaxis Expert Group. Prevention of
challenge. J Infect Dis
1990; 161: 281-5.
Endocarditis 2008 update from Therapeutic Guidelines: Antibiotic
22. Wang A, Athan E, Pappas PA et al. Contemporary clinical profile and out-
Version 13, and Therapeutic Guidelines: Oral and Dental Version 1,
come of prosthetic valve endocarditis. JAMA
2007; 297: 1354-61.
Melbourne: Therapeutic Guidelines Limited 2008.
23. Habib G, Tribouilloy C, Thuny F et al. Prosthetic valve endocarditis: who
7. Daly CG, Currie BJ, Jeyasingham MS et al. A change of heart: the new
needs surgery? A multicentre study of 104 cases. Heart
2005; 91: 954-9.
infective endocarditis prophylaxis guidelines. Australian Dental J
24. Edwards MB, Ratnatunga CP, Dore CJ, Taylor KM. Thirty-day mortality and
long-term survival following surgery for prosthetic endocarditis: a study
8. National Institute for Health and Clinical Excellence. Prophylaxis against
from the UK heart valve registry. Eur J Cardiothoracic Surg
1998; 14: 156-64.
infective endocarditis. Antimicrobial prophylaxis against infective endo-carditis in adults and children undergoing interventional procedures. UR
25. Farina G, Vitale N, Piazza L, De Vivo F, de Luca L, Cotrufo M. Long-term
http: // www.nice.org.uk/CG064 . March 2008.
results of surgery for prosthetic valve endocarditis . J Heart Valve Dis
1994; 3: 165-71.
9. Strom BL, Abrutyn E, Berlin JA et al. Dental and cardiac risk factors for
infective endocarditis. A population–based, case–control study. Ann
26. Agha Z, Lofgren RP, vanRuiswyk JV. Is antibiotic prophylaxis for bacterial
1998; 12: 761–9.
endocarditis cost-effective. Med Decis Making
2005; 25: 308-20.
10. Van der Meer JT, Thompson J, Valkenburg HA et al. Epidemiology of bac-
27. Idsoe O, Guthe T, Willcox RR et al. Nature and extent of penicillin side –
terial endocarditis in the Netherlands II. Antecedent procedures and use
reactions , with particular reference to fatalities from anaphylactic shock.
of prophylaxis. Arch Intern Med
1992; 152: 1869–73.
Bull World Health Organ
1968; 38: 159–88.
11. Lacassin F, Hoen B, Leport C et al. Procedures associated with infective
28. Lee P and Shanson D . Results of a UK survey of fatal anaphylaxis after
endocarditis in adults. A case control study. Europ Heart J
1995; 16: 1968-74.
oral amoxycillin. J Antimicrob Chemother
2007; 60: 1172–3.
12. Horstkotte D, Rosin H, Friedrichs W, Loogen F. Contribution for choosing
the optimal prophylaxis of bacterial endocarditis. Europ Heart J
1987; 8(Suppl J): 379-81.
13. Van der Meer JTM, van Wijk W, Thompson J et al. Efficacy of antibiotic
prophylaxis for prevention of native-valve endocarditis. Lancet
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