ANTIBIOTIC PROPHYLAXIS

FOR INFECTIVE
ENDOCARDITIS
Knowledge and Implementation of American Heart
Association guidelines among dentists and dental hygienists
in Alberta, Canada.

• Pankaj Jain, MD, et al

• JADA 146(10) October 2015

CONTENTS

• Infective endocarditis
• The Link to Dentistry
• Discussion of the Journal
• Guidelines for Antibiotic Prophylaxis for Infective Endocarditis
• A change in the NICE Guidelines
• Latest AHA Guidelines in 2017
• Guidelines Confusion
• National Antibiotic Guidelines
CAUSAL ORGANISMS

Organism % of IE cases

Streptococci 55%
viridans grp Streptococci 44% (from oral cavity)

Staphylococci 33%

Enterococci 6%

HACEK 5%

Candida 1%

Culture negative 1%
SYMPTOMS OF INFECTIVE
ENDOCARDITIS

• 5 Classic Signs of IE found in as many as 50% of

patients
• Petechiae
• Subungual haemorrhages
• Osler nodes
• Janeway lesions
• Roth spots
• Signs of Neurologic • Other signs
disease (40%) • Splenomegaly
• Stiff neck
• Embolic stroke with • Delirium
focal neurologic • Paralysis, hemiparesis,
deficits aphasia
• Conjunctival haemorrhage
• Intracerebral • Gallops
haemorrhages • Pallor
• Multiple • Rales
microabscesses • Cardiac arrhythmia
• Pericardial rub
• Pleural effusion rub
DUKE’S DIAGNOSTIC
CRITERIA
RISK OF DEVELOPING IE

• Steckelberg and Wilson estimated the lifetime risk of IE per

100,000 patient years in different groups:
• 5 cases per 100,000 patient years for the general
population with no known cardiac
• 52 for heart murmur or rheumatic fever patients (x10)*
• 383 for patients with a prosthetic valve (x75)*
• 740 for patients with previous history of IE (x150)*
• 2160 for patients with a prosthetic valve + previous history
of IE (x430)*
THE LINK TO DENTISTRY

• The concept that

bacteria released into
the circulation during
invasive dental
procedures might
cause IE was first
suggested by Lewis &
Grant in 1923.
• In 1935, Okell & Elliot demonstrated that 61%
of patients had positive blood cultures for
viridans group of Streptococci following a
dental extraction
• They also showed that oral viridans group
Streptococci could be identified in the
damaged heart tissue of 35-45% of IE cases
• It was assumed that oral bacteria entering the
circulation during invasive dental procedures
• Settled on heart valves of susceptible
individuals
• So the idea developed that giving antibiotic
prophylaxis before procedures might prevent
IE by killing any bacteria that entered the
circulation before they could reach the heart.
LET’S TALK ABOUT THE
STUDY…
AIM OF THE STUDY

• Determine how dentists and dental hygienists

interpret the AHA 2007 guidelines
• One objective of the AHA 2007 guidelines was
to reduce ambiguities and inconsistencies and
to provide greater clarity for patients and
health care providers
MATERIALS AND METHODS

• Study design: Cross-sectional survey

• Study population:
• Inclusion criteria: dentists and dental hygienists
in full- or part-time practice in Alberta, Canada.
• Exclusion: Retired professionals and those in
trainings
• Sampling method: Random number generator
• Sample size: 450 dentists + 450 dental hygienists
• Survey (5 parts):
• Part I: Use of IE prophylaxis by type of dental
procedure
• Part II: Recommendation for prophylaxis by cardiac
lesion
• Part III: factors influencing prophylaxis use, e.g.
patient preference
• Part IV: Demographic information of practitioner
• Part V: Awareness of 2007 AHA guidelines
• Statistical Analysis
• Data entry: REDCap
• Data analysis: IBM SPSS Statistics 20.0 (IBM)
• Computed descriptive statistics and comparisons
between groups with Chi-square test or Fisher exact test,
with P>0.05 as statistically significant
• Logistic regression to assess association between
participant characteristics and correctly recommending
IE prophylaxis
• Benjamini-Hochberg procedure for multiple comparisons
RESULTS

• Response: 149 dental hygienists (33%) and

194 dentists (43%)
IE PROPHYLAXIS BY
DENTAL PROCEDURE
IE PROPHYLAXIS BY CARDIAC
OTHER FACTORS INFLUENCING
AWARENESS OF THE AHA 2007
GUIDELINES
SUMMARY OF UNIVARIATE AND
MULTIVARIATE
LOGISTIC REGRESSION ANALYSES
DISCUSSION

• Much heterogeneity among both dentists and

dental hygienists in terms of dental
procedures for which they recommend
antibiotic prophylaxis
• Dental hygienists, relative to dentists, had
less understanding of cardiac lesions.
However, even among dentists, there was a
substantial proportion that did not
recommend prophylaxis in a manner
consistent with AHA prophylaxis.
• Patients reluctant to stop antibiotic
prophylaxis - patient/caregiver anxiety
• Cardiologists recommendations had an
important influence
• Correctly indicating the needs for antibiotic
prophylaxis for all 4 high-risk lesions was
associated with having to refer the guidelines
when completing the survey
CONCLUSION OF THE
SURVEY

• Heterogeneity in antibiotic prophylaxis

practice among dentists and dental hygienists
• Need for placing greater emphasis on IE
prophylaxis education
• Keep AHA guidelines in readily accessible
place for ease of referring.
CRITICAL APPRAISAL

• An appropriate method (questionnaire) used to conduct survey

• Questionnaire was adequately piloted
• Random sampling method reduced selection bias
• Attempted to reduce volunteer bias by increasing number of volunteers
with incentive and sending reminders
• Conclusion drawn from survey was of significant value
• Limitations:
• answers provided in the survey may not be what has been practiced by
practitioners
• volunteers who responded may have more knowledge regarding the
guidelines compared to those who did not, resulting in inevitable
volunteer bias
GUIDELINES OF ANTIBIOTICS
PROPHYLAXIS FOR IE
• In 1955, AHA produced the first guidelines
recommending antibiotic prophylaxis prior to
dental invasive procedures
• In the UK, British Society for Antimicrobial
Chemotherapy (BSAC) produced similar
guidelines
• As did professional organisations of other
countries
• Antibiotic prophylaxis quickly became the
worldwide standard of care for preventing IE
in ‘at risk’ patients
• However, a RCT has never been performed.
Thus, evidence of efficacy of antibiotic
prophylaxis is lacking.
• Prior to 2007, most countries recommended antibiotic
prophylaxis for
• Patients at ‘Moderate-Risk’ for IE
• History of rheumatic fever
• Native valve disease, e.g. mitral valve prolapse
• Congenital heart valve anomalies, e.g. bicuspid valve
• Patients at ‘High-Risk’ for IE
• Previous history of IE
• Prosthetic or repaired heart valve
• Patients with certain congenital heart conditions
ANTIBIOTIC PROPHYLAXIS
FOR IE IN THE U.K.

• In 2006, BSAC reviewed their guidelines

• Due to the lack of evidence for efficacy in
‘Moderate-Risk’ patients, they recommended
that it’s only restricted to ‘High-Risk’ patients.
• This cause outrage among U.K. cardiologists,
demanding the issue to be re-reviewed
• As a result, it was referred to NICE - National
Institute for Health & Care Excellence
NICE GUIDELINES 2008
• In March 2008
• NICE recommended “the complete cessation antibiotic prophylaxis for
dental, and all other, invasive procedures.”
• Rationale:
• Lack of RCT evidence of antibiotic prophylaxis efficacy
• Results of health-economic analysis concluded that antibiotic prophylaxis
was not cost-effective
• there is no consistent association between having an interventional
procedure, dental or non-dental, and the development of IE
• regular toothbrushing almost certainly presents a greater risk of IE than a
single dental procedure because of repetitive exposure to bacteraemia
with oral flora
• 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
GUIDELINES IN OTHER
COUNTRIES

• In 2007, AHA changed it’s guidelines:

• It recommended that antibiotic prophylaxis
should stop for those at ‘Moderate-Risk’ for
IE but should continue for those at ‘High-
Risk’ undergoing invasive dental
procedures.
• In 2009, the ESC and everyone else in the
world followed suit.
doi:10.1136/openhrt-2016-
000498.
SO WHAT HAPPENS AFTER
THE NICE GUIDELINES 2008?
Incidence of infective 
endocarditis in England, 2000–
13: a secular trend, interrupted 
time­series analysis
Mark J Dayer, Simon Jones, Bernard 
Prendergast, Larry M Baddour, Peter B 
Lockhart, Martin H Thornhill 

doi:10.1016/s0140-
6736(14)62007-9
doi:10.1016/s0140-
6736(14)62007-9
doi:10.1016/s0140-
6736(14)62007-9
doi:10.1016/s0140-
6736(14)62007-9
• Conclusion: Identified temporal association but unable to prove a
causal relation
• Suggests: antibiotic prophylaxis might be beneficial in preventing
infective endocarditis
• However, needs to weighed against potential costs of giving
antibiotic prophylaxis
• Risk of Adverse Drug Reactions to Antibiotic Prophylaxis
• The financial cost of Antibiotic Prophylaxis vs Treating Infectious
Endocarditis
• The risk of encouraging the development of antibiotic resistant
organisms
RISK OF ADVERSE DRUG
REACTIONS TO ANTIBIOTIC
PROPHYLAXIS
• Journal: Incidence and nature of adverse reactions to antibiotics used as
endocarditis prophylaxis
• Methods: Assessing all UK ‘Yellow Card’ for Adverse Drug Reaction (ADR)
reports for the last 45 years
• Results:
• Amoxicillin: 0 deaths & 23 non-fatal ADRs/million Rx
• Clindamycin: 12.6 deaths & 149.1 non-fatal ADRs/million Rx (mainly due
to C. Difficile infections)
• ADR is considerably worse for Clindamycin compared to Amoxicillin, but
still comparatively low in overall terms
• Amoxicillin is very safe in those without a history of amoxicillin allergy
FINANCIAL COST OF ANTIBIOTIC
PROPHYLAXIS VS TREATMENT OF
INFECTIVE ENDOCARDITIS
• Journal: The Cost-Effectiveness of Antibiotic Prophylaxis for Patients
at Risk of Infective Endocarditis
• The analysis demonstrated:
• Antibiotic prophylaxis is cheap but treating is less so
• Amoxicillin as prophylaxis would save NHS UK 5.5-8.2 million
pounds per year
• Clindamycin was also cost-saving but less so if compared to
amoxicillin
• Amoxicillin antibiotic prophylaxis is cheap even if it only prevents
1.4 IE cases/year
• Lancet Data suggests it prevents 419 IE cases/year
RISK OF ENCOURAGING THE
DEVELOPMENT ANTIBIOTIC RESISTANT
ORGANISMS

• Unfortunately, there are no data concerning

the risk of inducing antibiotic resistance
associated with AP.
• However, most concern relates to the use of
lower dose therapeutic antibiotic regimens
over several days and not to the use of a
single high dose of a bactericidal antibiotic,
such as amoxicillin.
THE AUSTRALIAN GUIDELINE FOR PREVENTION,
DIAGNOSIS
AND MANAGEMENT OF ACUTE RHEUMATIC FEVER
AND RHEUMATIC HEART DISEASE (2012)

• Patients indicated for IE

• Patients with prosthetic valves
• Patients with established RHD
• Patients receiving secondary prophylaxis (those already
receiving penicillin should be offered a different antibiotic
for prophylaxis)
• Excluded
• Patients with history of Acute Rheumatic Fever but no
vulvular damage
• Recommends preprocedure use of antiseptic
mouthwash
• recommend the use of an antiseptic mouth rinse
(such as chlorhexidine or povidone–iodine)
immediately before dental procedures to help
reduce the incidence and magnitude of
bacteraemia.
• Rinsing with 7.5% povidone–iodine can reduce the
incidence and magnitude of bacteraemia, and
influences the incidence of streptococcal
bacteraemia.
ESC GUIDELINE REVIEW
OUTCOME

• 1st September 2015

• Concluded that:
• “Antibiotic prophylaxis should be given before invasive
dental procedures to all patients at high-risk of
infective endocarditis”
• Risk assessment done for this recommendation
concluded that:
• “The risk of not giving antibiotic prophylaxis outweighs
any risk of giving it”
RECOMMENDED
PROPHYLAXIS BY ESC
GUIDELINE

• Alternatively, , cephalexin 2 g i.v. for

adults or 50 mg/kg i.v. for children,
cefazolin or ceftriaxone 1 g i.v. for
adults or 50 mg/kg i.v. for children.
NICE GUIDELINE REVIEW
OUTCOME

• “Antibiotic prophylaxis against infective

endocarditis is not recommended for people
undergoing dental procedures”
NICE GUIDELINE REVIEW
OUTCOME

• “Antibiotic prophylaxis against infective

endocarditis is not recommended routinely for
people undergoing dental procedures”
• A small, but significant change
• The ridged assertion that antibiotic
prophylaxis should not be given is replaced
with a recognition that it is appropriate for
some individuals
• As pointed out by the CEO of NICE:
“This amendment should now make clear that
in individual cases antibiotic prophylaxis may
be appropriate”
• However, there was lack of information
regarding:
• Which patients should be considered for
antibiotic prophylaxis
• Which dental procedures should be
considered for antibiotic prophylaxis
• What antibiotic prophylaxis should be used
2017 AHA/ACC FOCUSED UPDATE OF THE 2014 AHA/ACC
FOR THE MANAGEMENT OF PATIENTS WITH VALVULAR
HEART DISEASE
CPG PREVENTION, DIAGNOSIS &
MANAGEMENT OF IE (MALAYSIA)
（ 2017 ）
GUIDELINE CONFUSION
• Most regulatory bodies now require clinicians:
• To make patients aware of all the risks associated with the
treatment
• And the alternative treatment options available
• Patient must then be allowed to decide for themselves what
treatment they want.
• Patients who are at risk of IE must be informed of that risk and the
different views about the role of antibiotic prophylaxis in reducing
that risk
• They should then be allowed to decide for themselves if they wish
to have antibiotic prophylaxis or not
• Ideally, cardiologists should take responsibility for identifying which
patients are at high-risk and inform the patient’s dentist in writing
• Patient advice
• Importance of maintaining good oral health and
hygiene
• The risks of undergoing invasive procedures,
including non-medical procedures such as body
piercing or tattooing
• Educate patients regarding signs and symptoms of
infective endocarditis and when to seek for expert
advice
NATIONAL ANTIBIOTIC
GUIDELINE 2014
CHEMOPROPHYLAXIS
REFERENCE

• J Am Dent Assoc. 2015 Oct;146(10):743-50. doi: 10.1016/j.adaj.2015.03.021

• European Heart Journal, Volume 36, Issue 44, 21 November 2015, Pages 3075–3128,
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Lockhart, M. McGurk, D. Shanson, B. Prendergast & J. B. Chambers, BDJ volume
221,pages112–114 (12 August 2016)
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(2015). Incidence of infective endocarditis in England, 2000–13: a secular trend, interrupted
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disease (2nd edition)
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Endocarditis