Development of new guidelines for antibiotic prophylaxis for dental procedures in patients at risk of infective endocarditis
Submitting InstitutionUniversity College London
Unit of AssessmentAllied Health Professions, Dentistry, Nursing and Pharmacy
Summary Impact TypeHealth
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Dentistry, Public Health and Health Services
Summary of the impact
Infective endocarditis (IE) is a rare but life-threatening disorder that
may arise as a consequence of bacteraemia following invasive procedures
such as those of dentistry. Research at the UCL Eastman Dental Institute
has detailed the dental causes, prevalence and character of bacteraemia
following dental procedures and demonstrated that everyday oral health
activities are more likely to be a cause of bacteraemia than invasive
dentistry. The research outcomes informed 2008 NICE guidelines that
recommended that antibiotic prophylaxis solely to prevent IE should not be
given to people at risk of IE undergoing dental and non-dental procedures.
This has since caused a 78.6% fall in related antibiotic prescribing, a
cost-saving of approximately £4m to the NHS in England and will reduce the
threats of fatal anaphylaxis and antibiotic resistance.
Infective endocarditis (IE) is a rare disorder but with significant
morbidity and mortality. Oral streptococci may cause approximately 48% of
confirmed cases of endocarditis. Until 2008, it was standard practice to
give antibiotic prophylaxis to at-risk patients prior to certain dental
procedures to reduce the risk of IE. The number of patients affected was
approximately 130,000 per year. However, there was no strong evidence to
support this practice, and some researchers questioned its effectiveness.
This uncertainty led to a programme of research at the UCL Eastman Dental
Institute (UCL EDI) to understand the processes involved.
A review by Roberts  concluded that everyday procedures such
as clenching and tooth-cleaning are more likely to cause IE than single
invasive dental procedures and that the benefit of antibiotic prophylaxis
prior to dental treatment was questionable.
Roberts, Lucas, Spratt and Wilson thus undertook a programme of work from
the late 1990s onwards to understand the events that lead to bacteraemia
and to determine its prevalence and intensity. They established that
simple dental procedures (rubber dam placement, use of fast or slow
drills, placement of simple restorations and orthodontic therapy) induced
bacteraemia [2, 3, 4]. A study subsequently demonstrated that
bacteraemia was as likely to develop as a consequence of tooth brushing at
home as from cleaning or scaling by a dental professional ;
indeed tooth-brushing was found to be an important factor in cumulative
dental bacteraemia and that over one year, bacteraemia due to
tooth-brushing was many millions of times greater than a single dental
extraction . A later study of a cohort of 500 children to
determine the duration, prevalence and intensity of bacteraemia following
dental extractions demonstrated that bacteraemia could be detected after
10 seconds and up to about 11 minutes following extraction and that a rich
microbiota was present in blood with 42 different taxa being
Roberts subsequently co-authored a Cochrane review on antibiotics for the
prophylaxis of bacterial endocarditis in dentistry  in which it
was concluded that there was no evidence as to whether penicillin
prophylaxis is effective or ineffective against bacterial endocarditis in
people at risk of endocarditis who are about to undergo an invasive dental
procedure. Indeed the review demonstrated that there was a lack of
evidence to support the previously published guidelines.
The experimental evidence of the Eastman group and the literature review
subsequently served to underpin the development of NICE guidelines for the
use of antibiotic prophylaxis for invasive dental (and other) procedures.
Researchers at UCL EDI who contributed to this work included: Professor
Graham Roberts (Head of Paediatric Dentistry); Dr Victoria Lucas (Senior
Clinical Lecturer); Professor Mike Wilson (Head of Microbiology); Dr David
Spratt (Reader in Microbial Ecology); Ruth Holt (Senior Lecturer); Dr
Aviva Petrie (Senior Lecturer in Statistics); Roger Davis (Consultant and
Honorary Senior Lecturer in Special Care Dentistry).
References to the research
 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 Sept-Oct;20(5):317-25. Copy available.
 Roberts GJ, Gardner P, Longhurst P, Black A, Lucas VS. Intensity of
bacteraemia associated with conservative dental procedures in children.
BDJ. 2000 Jan;188:95-8. Copy available.
 Roberts GJ, Lucas VS, Omar J. Bacterial endocarditis and
orthodontics. J R Coll Surg Edinb. 2000 Jun;45(3):141-5. Copy available.
 Lucas VS, Omar J, Vieira A, Roberts GJ. The relationship between
odontogenic bacteraemia and orthodontic treatment procedures. Eur J Orth.
 Lucas V, Roberts GJ. Odontogenic bacteremia following tooth cleaning
procedures in children. Pediatr Dent. 2000 Mar-Apr;22(2):96-100. Copy
Details of the impact
The research described above provided substantial evidence to challenge
the existing guidelines on antibiotic prophylaxis (typically in the UK 3g
of amoxicillin or 600mg of clindamycin) prior to a relevant procedure).
Roberts was co-opted onto the NICE Guideline Development Group as adviser
on this topic. In 2008, NICE issued Clinical Guideline 64, Prophylaxis
against infective endocarditis [a]. The work of the Roberts
group was influential in this document and 7 papers were cited at 16
points throughout the document. The guidelines recommended that antibiotic
prophylaxis used solely to prevent IE should not be given to people at
risk of IE undergoing dental and non-dental procedures. Four points were
highlighted that underpinned this recommendation and work by the Roberts
group was used to support 3 of these:
- there is no consistent association between having an interventional
procedure, dental or non-dental, and the development of IE (cites
- regular tooth brushing almost certainly presents a greater risk of IE
than a single dental procedure because of repetitive exposure to
bacteraemia with oral flora (cites references  and )
- the clinical effectiveness of antibiotic prophylaxis is not proven
(cites reference )
- antibiotic prophylaxis against IE for dental procedures may lead to a
greater number of deaths through fatal anaphylaxis than a strategy of no
antibiotic prophylaxis, and is not cost effective.
As a consequence of the NICE guidelines, there has been a demonstrable
change in clinical practice, with a resulting decrease in antibiotic
prescribing for dental procedures and infective endocarditis. A review in
2011 revealed that prescriptions in England reduced by 79% in the two
years after guidelines were issued with no increase in the rate of
infective endocarditis [b]. A review of dental prescribing in
Wales also reported that dental prescriptions for amoxicillin 3g sachets
and clindamycin capsules decreased sharply after the publication of the
NICE guidelines in 2008 [c]. Overall this represents a reduction
of over half a million doses over a five-year period for the two
countries. The reduction of unnecessary antibiotic prescribing has three
key impacts: (i) improved patient safety through reduced adverse reactions
to antibiotics; (ii) a cost-saving to the NHS through lower wastage; (iii)
a reduction in antibiotic use helping to prevent an increase in antibiotic
resistance in the community.
Improved patient safety: The guidelines discuss anaphylaxis as one
of the reasons for their recommendation. It has been estimated that
approximately 20 individuals per million patients who receive a dose of
penicillin suffer a fatal anaphylactic reaction [d]. Approximately
500,000 doses have been avoided and an estimated 10 lives likely to have
been saved and countless episodes of anaphylaxis avoided (in the UK
Cost-savings to the NHS: Prior to the guidelines, approximately
129,000 doses were prescribed per year and this reduced to 27,504 doses
per year in the two years after the guidelines were issued. This
represents a reduction of over half a million doses over the five years
and a consequent saving of approximately £4m in prescription fees
(calculated from data in [b]).
A reduction in antibiotic use: As detailed above, approximately
500,000 fewer doses of antibiotics were prescribed to patients in the
period. The inappropriate and overuse of antibiotics in the past has
provided an extremely strong selective pressure for bacteria to evolve and
acquire a myriad of different resistance mechanisms. As highlighted by the
Chief Medical Officer of England, bacterial resistance to antimicrobials
now represents one of the most urgent problems facing public health and
modern healthcare. Once antibiotics become ineffective, increases in
morbidity and premature mortality will follow.
Changes in international guidelines: The research described above
has also had an impact on guidelines around the world, which have been
reviewed and modified using evidence generated by the UCL EDI team.
Roberts was acknowledged as an international expert by the American Heart
Association in 2007 prior to his work with NICE and six papers by the
Roberts group were used to support their recommendations. The research
also informed the 2008 American Academy of Pediatric Dentistry guidelines
for antibiotic prophylaxis for dental patients at risk of infection [e]
and the 2009 European Society of Cardiology Guidelines on the prevention,
diagnosis, and treatment of infective endocarditis [f] leading to
a change in their clinical recommendations. Other international bodies
have used the above guidelines to inform their own national
recommendations. For example, in Australia, national guidelines twice
reference work by Roberts and colleagues [g].
Sources to corroborate the impact
[a] NICE guidance. CG064 c against infective endocarditis. 2008:
(Appendices, including references, here: http://guidance.nice.org.uk/index.jsp?action=download&o=40042)
[b] Thornhill MH, Dayer MJ, Forde JM, Corey GR Corey, Hock G, Chu VH,
Couper DJ, Lockhart PB. Impact of the NICE guideline recommending
cessation of antibiotic prophylaxis for prevention of infective
endocarditis: before and after study. BMJ 2011; 342 doi: http://dx.doi.org/10.1136/bmj.d2392.
[c] Karki AJ, Holyfield G, Thomas D. Dental prescribing in Wales and
associated public health issues. Br Dent J. 2011 Jan 8;210(1):E21. http://dx.doi.org/10.1038/sj.bdj.2010.1179
[d] Prevalence data taken from: Gould FK, Elliott TSJ, Foweraker J, et
al. Guidelines for the prevention of endocarditis: report of the Working
Party of The British Society for Antimicrobial Chemotherapy—authors'
response. J Antimicrob Chemother 2006;58:896-8. http://dx.doi.org/10.1093/jac/dkl299
[e] American Academy on Pediatric Dentistry Clinical Affairs Committee;
American Academy on Pediatric Dentistry Council on Clinical Affairs.
Guideline on antibiotic prophylaxis for dental patients at risk for
infection. Pediatr Dent. 2008-2009;30(7 Suppl):215-8. http://www.guideline.gov/content.aspx?id=34766
[f] Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I,
Moreillon P, de Jesus Antunes M, Thilen U, Lekakis J, Lengyel M, Müller L,
Naber CK, Nihoyannopoulos P, Moritz A, Zamorano JL; 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 Oct;30(19):2369-413. http://dx.doi.org/10.1093/eurheartj/ehp285
[g] Daly CG, Currie BJ, Jeyasingham MS, Moulds RF, Smith JA, Strathmore
NF, Street AC, Goss AN. A change of heart: the new infective endocarditis
prophylaxis guidelines. Aust Dent J. 2008 Sep;53(3):196-200; quiz 297.