2. Infective endocarditis (IE) is a peculiar disease for at least three
reasons:
First, neither the incidence nor the mortality of the disease
have decreased in the past 30 years. Despite major advances in
both diagnostic and therapeutic procedures, this disease still
carries a poor prognosis and a high mortality.
Secondly, IE is not a uniform disease, but presents in a variety of
different forms, varying according to the initial clinical
manifestation, the underlying cardiac disease (if any), the
microorganism involved, the presence or absence of
complications, and underlying patient characteristics
Thirdly, guidelines are often based on expert opinion because of
the low incidence of the disease, the absence of randomized trials,
and the limited number of meta-analyses.
3. IE is clearly an evolving disease, with changes in its
microbiological profile, a higher incidence of healthcare-
associated cases,elderly patients,and patients with
intracardiac devices or prostheses.
Conversely, cases related to rheumatic disease have
become less frequent in industrialized nations.
In addition, several new national and international
guidelines or state-of-the-art papers have been published
in recent years.
Unfortunately, their conclusions are not uniform,
particularly in the field of prophylaxis, where conflicting
recommendations have been formulated.
Clearly, an objective for the next few years will be an
attempt to harmonize these recommendations.
4. Infective endocarditis (IE) is a microbial
infection of the endothelial surface of the
heart or iatrogenic foreign bodies like
prosthetic valves or other intracardiac devices
Infective Endarteritis – AV shunts,
Arterioarterial shunts, Coarctation of aorta
5. The prototypic lesion
The vegetation
Variable in size
Amorphous mass of fibrin & platelets
Abundant organisms
Few inflammatory cells
6.
7. NonbacterialThrombotic Endocarditis
Endothelial injury
Hypercoagulable state
Lesions seen at coaptation points of valves
▪ Atrial surface mitral/tricuspid
▪ Ventricular surface aortic/pulmonic
Modes of endothelial injury
▪ High velocity jet
▪ Flow from high pressure to low pressure chamber
▪ Flow across narrow orifice of high velocity
Platelet-fibrin thrombi
8. Transient bacteremia
Traumatization of mucosal surface colonized
with bacteria (oral, GI)
Low grade, cleared in 15-30 minutes
Susceptibility to complement-mediated
bacterial killing
Leads to concept of prophylaxis
9. • Pathology
– NVE infection is largely confined to leaflets
– PVE infection commonly extends beyond valve
ring into annulus/periannular tissue
• Ring abscesses
• Septal abscesses
• Fistulae
• Prosthetic dehiscence
10. • 1.7 to 6.2 cases per 100,000 population per
year in US
• The cumulative rate of prosthetic valve
endocarditis is 1.5 to 3.0% at 1 year after
valve replacement.
• 3 to 6% at 5 years; the risk is greatest during
the first 6 months after valve replacement.
• Men predominate in most case series, with
male-to-female ratios ranging from 2:1 to 9:1
11. The epidemiological profile of IE has changed substantially
over the last few years, especially in industrialized nations.
Once a disease affecting young adults with previously well-
identified (mostly rheumatic) valve disease, IE is now
affecting older patients who more often develop IE as the
result of health care-associated procedures, either in patients
with no previously known valve disease or in patients with
prosthetic valves.
A recent systematic review of 15 population-based
investigations accounting for 2371 IE cases from seven
developed countries (Denmark, France, Italy,The
Netherlands, Sweden, the UK, and the USA) showed an
increasing incidence of IE associated with a prosthetic valve,
an increase in cases with underlying mitral valve prolapse,
and a decrease in those with underlying rheumatic heart
disease.
12. Newer predisposing factors have emerged—valve
prostheses, degenerative valve sclerosis, intravenous drug
abuse—associated with increased use of invasive
procedures at risk for bacteraemia, resulting in health
care-associated IE.
In a pooled analysis of 3784 episodes of IE, it was shown
that oral streptococci had fallen into second place to
staphylococci as the leading cause of IE. However, this
apparent temporal shift from predominantly streptococcal
to predominantly staphylococcal IE may be partly due to
recruitment/referral bias in specialized centres, since this
trend is not evident in population-based epidemiological
surveys of IE.
In developing countries, classical patterns persist.
13. • Structural heart disease
– Rheumatic, congenital, aging
– Prosthetic heart valves
• Injected drug use
• Invasive procedures (Intracardiac pacemaker,
ICD , AV Fistula)
• Indwelling vascular devices
• Other infection with bacteremia (e.g.
pneumonia, meningitis)
• Immunocompromised states
• History of infective endocarditis
14.
15. 30-65% of native valve endocarditis
Normal oral commensals
A group, composed of several species:
S. mitior, S. sanguis, S. mutans,etc.
Alpha-hemolytic, non-typable
Typical agents of classic “SBE”
Strep. viridans
16. • S. bovis
– Lancefield group D
– Gut flora: associated with GI pathology
• S. pneumonia
– 1-3% of cases of IE with predilection for AV
– Usually, in those with immune suppression
• DM and Alcoholism
• Group B Streptococci
– Elderly with chronic disease
17. Normal inhabitant of GI tract.
Frequently encountered in UTIs.
Up to 40% of cases without identified
underlying predisposition to IE.
Difficult to treat due to drug resistance.
18. Coagulase Positive (Staph. aureus)
a major causative agent in all populations of IE
typically produces “acute” IE
▪ fulminant, rapidly progressive with few immunologic
signs.
▪ CNS complications in 30-50%
Coagulase Negative (Staph. Epi)
Major cause of PVE. 3-8% of NVE.
19. • Hemophilus, Actinobacillus, Cardiobacterium,
Eikenella, Kingella
• Gram negative inhabitants of the upper
airways.
• Large vegetations, high likelihood of
embolization.
• Slow growing: hold cultures for 3 weeks.
• Traditionally sensitive to beta lactams, now
some produce beta lactamase.
22. • Blood culture sterile in 31 % (western data)
• Sterile culture in India – 48 to 54 %
• Blood culture is positive only on 67.7% of the
cases in recently published data from India
• Causes
– Antibiotic therapy before blood culture
– Fastidius or atypical organisms do not grow in
routine culture media
– Fungal or viral Endocarditis
23. Accounts for 25% of
cases of IE in US.
5:1 male:female
Pre-existing valvular
diseases uncommon.
Variable
microbiology.
Mortality<10%.
AV
6%
MV
24%
TV
70%
24. Affects 3% of prosthesis patients.
Highest risk in first 6 months post op.
Accounts for 10-20% of all IE cases.
“Early” (<2 months)-Staph epi
“Late” (after 2 months)- mimics NVE
Increased risk in…
Males
Blacks
Multiple valve replacement
26. Year Primary Regimens for Dental Procedures
1955 Aqueous penicillin 600 000U and procaine penicillin
600 000 U in oil containing 2% aluminum monostearate
administered IM 30 minutes before the operative procedure
1957 For 2 days before surgery, penicillin 200 000 to
250000 U by mouth 4 times per day. On day of surgery,
aqueous penicillin 600 000 U with procaine penicillin
600000 U IM 30 to 60 minutes before surgery. For 2 days
after, 200000 to 250000 U by mouth 4 times per day.
1960 Step I: prophylaxis 2 days before surgery with procaine
penicillin 600 000 U IM on each day
Step II: day of surgery: procaine penicillin 600 000 U
IM supplemented by crystalline penicillin 600 000 U
IM 1 hour before surgical procedure
Step III: for 2 days after surgery: procaine penicillin
600000 U IM each day
27. 1965 Day of procedure: procaine penicillin 600 000 U,
supplemented by crystalline penicillin 600 000 U IM 1
to 2 hours before the procedure For 2 days after
procedure: procaine penicillin 600 000 U IM each day
1972 Procaine penicillinG 600 000 U mixed with crystalline
penicillinG 200 000 U IM 1 hour before procedure and once
daily for the 2 days after the procedure
1977 Aqueous crystalline penicillinG (1 000 000 U IM)
mixed with procaine penicillinG (600 000 U IM) 30
minutes to 1 hour before procedure and then penicillin
V 500 mg orally every 6 hours for 8 doses.
1984 PenicillinV 2 g orally 1 hour before, then 1 g 6 hours
after initial dose
1990 Amoxicillin 3 g orally 1 hour before procedure, then
1.5 g 6 hours after initial dose
1997 Amoxicillin 2 g orally 1 hour before procedure
28. Endocarditis Prophylaxis Recommended:
High-risk category
-Prosthetic cardiac valves, including bioprosthetic and homograft
valves
-Previous bacterial endocarditis
-Complex cyanotic congenital heart disease (eg, single ventricle
states, transposition of the great arteries, tetralogy of Fallot)
-Surgically constructed systemic pulmonary shunts or conduits
Moderate-risk category
-Most other congenital cardiac malformations (other than above and
below)
-Acquired valvar dysfunction (eg, rheumatic heart disease)
-Hypertrophic cardiomyopathy
-Mitral valve prolapse with valvar regurgitation and/or thickened
leaflets
29. Endocarditis Prophylaxis Not Recommended:
Negligible-risk category (no greater risk than the general
population)
- Isolated secundum atrial septal defect
-Surgical repair of atrial septal defect, ventricular septal defect, or
patent ductus arteriosus (without residua beyond 6 mo)
-Previous coronary artery bypass graft surgery
-Mitral valve prolapse without valvar regurgitation1
-Physiologic, functional, or innocent heart murmurs1
-Previous Kawasaki disease without valvar dysfunction
-Previous rheumatic fever without valvar dysfunction
-Cardiac pacemakers (intravascular and epicardial) and implanted
defibrillators
30. Assumptions:
Bacteremia with organisms known to cause IE occurs in
assoc. with invasive dental/GI/GU procedures
Antibiotic prophylaxis was proven effective in animals
Antibiotic prophylaxis thought to be effective in human
31. The reported incidence of transient bacteraemia after dental
procedures is highly variable and ranges from 10 to 100%.
In contrast, transient bacteraemia is reported to occur frequently
in the context of daily routine activities such as tooth brushing,
flossing, or chewing. It therefore appears plausible that a large
proportion of IE-causing bacteraemia may derive from these daily
routine activities.
In addition, in patients with poor dental health, bacteraemia can
be observed independently of dental procedures, and rates of
post-procedural bacteraemia are higher in this group.
These findings emphasize the importance of good oral hygiene
and regular dental review to prevent IE.
Risks and benefits of prophylaxisThe following considerations are
critical with respect to the assumption that antibiotic prophylaxis
can efficiently prevent IE in patients who are at increased lifetime
risk of the disease
32. Increased lifetime risk of IE is not an ideal measure of the extent to which a
patient may benefit from antibiotic prophy- laxis for distinct procedures. A
better parameter, the procedure-related risk, ranges from 1:14 000 000 for
dental procedures in the average population to 1:95 000 in patients with
previous IE.These estimations demonstrate the huge number of patients that
will require treatment to prevent one single case of IE.
In the majority of patients, no potential index procedure preceding the
first clinical appearance of IE can be identified. Even if effectiveness and
compliance are assumed to approximate 100%, this observation leads to two
conclusions:
(i) IE prophylaxis can at best only protect a small proportion of patients; and
(ii) the bacteraemia that causes IE in the majority of patients appears to derive
from another source.
Antibiotic administration carries a small risk of anaphylaxis. However, no
case of fatal anaphylaxis has been reported in the literature after oral
amoxicillin administration for prophylaxis of IE.
Widespread and often inappropriate use of antibiotics may result in the
emergence of resistant microorganisms. However, the extent to which
antiobiotic use for IE prophylaxis could be implicated in the general problem of
resistance is unknown.
33. Lack of scientific evidence for the efficacy of infective
endocarditis prophylaxis
Studies reporting on the efficacy of antibiotic prophylaxis to
prevent or alter bacteraemia in humans after dental procedures
are contradictory,and so far there are no data demonstrating that
reduced duration or frequency of bacteraemia after any medical
procedure leads to a reduced procedure-related risk of IE.
Similarly, no sufficient evidence exists from case–control studies
to support the necessity of IE prophylaxis.
Even strict adherence to generally accepted recommendations
for pro- phylaxis might have little impact on the total number
of patients with IE in the community.
Finally, the concept of antibiotic prophylaxis efficacy itself has
never been investigated in a prospective randomized controlled
trial, and assumptions on efficacy are based on non-uniform
expert opinion, data from animal experiments, case reports,
studies on isolated aspects of the hypothesis, and contradictory
observational studies.
34. IE more likely due to frequent exposure to random
bacteremias from daily activities than from
bacteremia during dental/GI/GU procedure
Prophylaxis may prevent only small number of cases
of IE, even if 100% effective
Risk of antibiotic-assoc. adverse events exceeds the
benefit, if any, from prophylaxis
To reduce the risk of bacteremia from dental
procedure: maintaining good oral health and
hygiene is more important than Antibiotic
prophylaxis
36. No prospective, randomized, placebo-
controlled studies exist on efficacy of
Antibiotic prophylaxis in preventing IE after
dental procedure
37. Only patients with the highest risk of adverse
outcomes (heart failure, surgery, death) from
endocarditis:
1. Prosthetic cardiac valve
2. Previous IE
3. Cardiac transplant recipients who develop
cardiac valvulopathy
4. Congenital Heart Disease
38. Unrepaired cyanotic CHD
Tetralogy of Fallot,Transposition of GreatArteries,
including palliative shunts and conduits
Completely repaired congenital heart defect with
prosthetic material or device during 1st 6 months
after surgery
Repaired CHD with residual defects at or near a
prosthetic patch/device (which inhibit
endothelialisation)
40. “If it bleeds, give prophylaxis”
High-risk pts undergoing all dental procedures that
involve manipulation of gingival tissues OR
periapical region of teeth OR perforation of oral
mucosa
i.e. biopsies, suture removal, placing orthodontic bands
NO PROPHYLAXIS:
Xray, anesthetic injections, fluoride treatments
Shedding of deciduous teeth
Placement/adjustment of removable prosthodontic or
orthodontic appliances
41. Goal: cover StrepViridans
Single dose, 30-60 min prior to procedure
42. Quinolones or IVVancomycin not recommended for
prophylaxis due to concern of creating new drug
resistance
43. No published data linking respiratory tract
procedures and IE....
Consider prophylaxis for High-risk pts
undergoing Invasive Procedure in respiratory
tract with incision or biopsy of respiratory
mucosa:
▪ Tonsillectomy
▪ Adenoidectomy
▪ Bronchoscopy WITH biopsy (not for BAL alone)
▪ Respiratory tract procedure to drain abscess or empyema
44. No published data linking GI/GU procedures and
IE....
NO prophylaxis for GI/GU procedures
45. In patients who are HIGH-risk for IE:
The antibiotic regimen given to treat the skin
or musculoskeletal infection should contain
an Anti-staphylococcal Pencillin or
cephalosporin
If unable to take PO or Pencillin-allergic:
Clindamycin orVancomycin
46. Need high-risk patient PLUS high-risk procedure
High-risk pts:
1. Prosthetic cardiac valve
2. Previous IE
3. Cardiac transplants with valvulopathy
4. Congenital Heart Disease
High-risk procedures:
1. Dental: “If it bleeds, give prophylaxis”
2. Respiratory: Consider if pt will be cut or biopsied
3. GI/GU: never
48. If the dosage of antibiotic is inadvertently not
administered before the procedure, the
dosage may be administered up to 2 hours
after the procedure. However, the
administration of the dosage after the
procedure should be considered only when
the patient did not receive the pre-procedure
dose
49. In such cases , due to the likelihood of the
presence of penicillin-resistant bacteria in the
oral flora, the provider should select either
clindamycin, azithromycin, or clarithromycin for
IE prophylaxis for a dental procedure
50.
51. Bacteremia resulting from daily activities is much more likely
to cause IE than bacteremia associated with a dental
procedure.
Only an extremely small number of cases of IE might be
prevented by antibiotic prophylaxis even if prophylaxis is
100% effective.
Antibiotic prophylaxis is not recommended based solely on
an increased lifetime risk of acquisition of IE.
Antibiotic prophylaxis is no longer recommended for any
other form of CHD and otherValvular heart disease except
as mentioned above .
52. Antibiotic prophylaxis is reasonable for all dental
procedures that involve manipulation of gingival tissues
or periapical region of teeth or perforation of oral
mucosa only for patients with underlying high risk
cardiac conditions.
Antibiotic prophylaxis is reasonable for procedures on
respiratory tract or infected skin, skin structures, or
musculoskeletal tissue only for patients with underlying
high risk cardiac conditions.
Antibiotic prophylaxis solely to prevent IE is not
recommended for GU or GI tract procedures.
