Infective endocarditis is an infection of the heart valves or endocardium. It can involve one or more valves or the inner lining of the heart. This document provides definitions and classifications of infective endocarditis and discusses its epidemiology, microbiology, pathophysiology, clinical features, diagnosis, and treatment. Treatment involves antimicrobial therapy targeting the likely causative pathogens, with combinations of drugs preferred over monotherapy to achieve bactericidal concentrations and potentially shorten treatment duration. Surgery may also be required to treat sequelae of intracardiac lesions.

1. INFECTIVE ENDOCARDITIS
Dr. Basil Tumaini
Dr. Shamsherali Ebrahim
Residents Internal medicine, 11/01/2017
1

2. Outline
• Definition
• Classification
• Epidemiology and Microbiology
• Pathophysiology
• Clinical features
• Diagnosis
• Treatment
• Prophylaxis
• Complications
• Conclusion
• References
2

3. Definition
• Infective endocarditis is the infection of the
cardiac endothelium, most commonly the
valves
• It may involve:
– One or more valves
– Mural endocardium
– A septal defect
3

4. Classification
MODE OF ONSET
ACUTE
SUB ACUTE
NATURE OF VALVE
NATIVE VALVE
PROSTHETIC VALVE
SIDE OF THE HEART
RIGHT-SIDED
LEFT-SIDED
4

5. Active Endocarditis
 IE with fever and
positive blood cultures
or
 Active inflammatory
morphology at surgery
or
 Patient still under
antibiotic therapy or
 Histopathologic
evidence of active IE
Recurrence
 Relapse – repeat episode
caused by the same
organism < 6 mo from initial
episode
 Reinfection – Infection with
a different microorganism
or same organism > 6 mo
from initial episode
5

6. Epidemiology
• M:F ratio 3:1
• No racial predilection
• Case rate may vary between 2-3 cases
/100,000 to as high as 15-30/100,000
depending on incidence of I.V. drug abuse and
age of the population
6

7. Predisposing conditions
High risk
 Prosthetic cardiac valve
 Previous IE
 Congenital heart disease (unrepaired, repaired
within 6 mo, repaired with defects)
 cardiac transplant with valve disease
(surgically constructed systemic-to-pulmonary
shunts or conduits)
7

8. Predisposing conditions ...
Moderate risk
 Other congenital cardiac defects
 Acquired valvular dysfunction
 Hypertrophic cardiomyopathy
8

9. Predisposing conditions ...
Low/no risk
 Secundum ASD or surgically repaired ASD<VSD
 PDA
 MV prolapse
 Ischemic heart disease
 Previous CABG
9

10. Predisposing conditions ...
Opportunity for bacteremia
 IVDU
 Indwelling venous catheter
 Hemodialysis
 Poor dentition
 DM
 HIV
10

11. Frequency of valve involvement
• MV >> AV > TV > PV
• ƒBut in 50% of IVDU-related IE the tricuspid
valve is involved
11

12.  55-75% of patients with native valve endocarditis
(NVE) have underlying valve abnormalities
MVP
Rheumatic
Congenital
I.V drug abuse
 7-25% of cases involve prosthetic valves
 25-45% of cases predisposing condition can not be
identified
12

13. Adult population
• MVP
-prominent predisposing factor(7-20%)
-Accounts for 7 – 30% NVE in cases
• Rheumatic Heart Disease
-7 – 18% of cases in recent reported series
-Mitral site >women
-Aortic site >in men
• Congenital Heart Disease
-10 – 20% of cases in young adults
- 8% of cases in adults(PDA, VSD, bicuspid aortic valve)
Etiology: Strep (viridans, bovis, enterococci), Staph
13

14. • Intravenous Drug Abuse
– Risk is 2 – 5% per pt./year
– Tendency to involve right-sided valves
• Distribution in clinical series
–46 – 78% tricuspid
–24 – 32% mitral
– 8 – 19% aortic
– Underlying valve normal in 75 – 93%
– S. aureus predominant organism (>50%, 60-70%
of tricuspid cases), others strep, pseudomonas,
HACEK
14

15. • Prosthetic Valve Endocarditis (PVE)
– 10 – 30% of all cases in developed nations
– Cumulative incidence
• 1.4 – 3.1% at 12 months
• 3.2 – 5.7% at 5 years
– Mechanical valves more likely to be infected < 3 mo after
implantation
– Bioprosthetic valves > 1 year
– Early PVE (<60 days)
• Nosocomial (s. epi predominates)
– Late PVE (>60 days)
• Community (same organisms as NVE – strepto, staph)
• Others: Corynebacteria, HACEK, Fungal
15

16. Pediatric population
• The majority (75-90%) of cases after the
neonatal period are associated with an
underlying congenital abnormality
-Aortic valve
-VSD
-Tetralogy of Fallot
• Risk of post-op infection in children with IE is
50%
16

17. Organisms
Young
 S. aureus
 Coagulase negative staphylococci
 group B streptococci
Older
 Streptococci
17

18. 18

19. Pathophysiology
 Leaflet vegetations consist of platelet-fibrin
thrombi, WBCs, and bacteria
19
Microbial
pathogens
Valve
endothelium
Portal of entry Transient bacteremia
Host defences

20. Clinical Features
Systemic
• ƒfever (80-90%)
• chills
• weakness
• rigors
• night sweats
• weight loss
• anorexia
20

21. Clinical Features ...
Cardiac
• ƒDyspnea
• Chest pain
• Clubbing (subacute)
• ƒRegurgitant murmur (new onset or increased
intensity)
• ƒSigns of CHF (secondary to acute MR, AR)
21

22. Clinical Features ...
Embolic/Vascular
• ƒPetechiae over legs, splinter hemorrhages
(linear, reddish-brown lesion within nail bed)
• ƒJaneway lesions (painless, 5 mm, erythematous,
hemorrhagic pustular lesions on soles/palms)
• ƒFocal neurological signs (CNS emboli), headache
(mycotic aneurysm)
• ƒSplenomegaly (subacute)
• ƒMicroscopic hematuria, flank pain (renal emboli)
― active sediment
22

23. SPLINTER HEMORRHAGES IN NAIL BED
23

24. 24
JANEWAY LESIONS

25. Clinical Features ...
Immune complex
• ƒOsler’s nodes (painful, raised, red/brown, 3-
15 mm on digits)
• ƒglomerulonephritis
• ƒarthritis
• ƒRoth’s spots (retinal hemorrhage with pale
center)
25

26. OSLER’S NODE
26

27. ROTH SPOT
27

28. Diagnosis
• High index of suspicion in patients with
predisposing anatomy or behavior
• Increased predisposition
– Clinical Features
– Blood cultures
– Echocardiography
• TTE – 60% sensitivity
• TEE – 80 – 95% sensitive
– Modified Duke’s Criteria
• Sensitivity and Specificity – 80%

29. Major criteria include:
1. Positive blood culture with typical IE microorganism, defined as one of the
following:
– Typical microorganism consistent with IE from 2 separate blood cultures, as noted below:
• Viridans-group streptococci, or
• Streptococcus bovis including nutritional variant strains, or
• HACEK group, or
• Staphylococcus aureus, or
• Community-acquired Enterococci, in the absence of a primary focus
– Microorganisms consistent with IE from persistently positive blood cultures defined as:
• Two positive cultures of blood samples drawn >12 hours apart, or
• All of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart)
• Coxiella burnetii detected by at least one positive blood culture or antiphase I IgG antibody titer
>1:800
2. Evidence of endocardial involvement with positive echocardiogram defined as
– Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets,
or on implanted material in the absence of an alternative anatomic explanation, or
– Abscess, or
– New partial dehiscence of prosthetic valve or new valvular regurgitation (worsening or
changing of preexisting murmur not sufficient)
Minor criteria include:
1. Predisposing factor: known cardiac lesion, recreational drug injection
2. Fever >38°C
3. Evidence of embolism: arterial emboli, pulmonary infarcts, Janeway
lesions, conjunctival hemorrhage
4. Immunological problems: glomerulonephritis, Osler's nodes
5. Positive blood culture (that doesn't meet a major criterion) or serologic evidence of
infection with organism consistent with IE but not satisfying major criterion

30. 30

31. Culture
• Take the specimen correctly
– Avoid skin contaminants
– Adequate volume 20mls
• Label and package the specimen correctly
• Patient particulars
• Relevant medical history/suspected diagnosis
• Relevant clinician details
• Return address for results
• Date and time
• Appropriate transport and storage of specimen
– Avoid delay
– Appropriate storage media
• Timely performance of the test and feedback of results

32. 32

33. Treatment
• Multidisciplinary
• Antimicrobial therapy remains the
cornerstone of treatment
• Aims
– Eradicate infection
– Definitively treat sequelae of destructive intra-
cardiac and extra-cardiac lesions

34. • However, Bacterial eradication may be very
difficult
– High conc of organisms in the vegetation (10-100
billion bacteria per gram of tissue)
– Position deep within the thrombus
– Reduced metabolic and reproductive state
– Interference of fibrin and white cells to antibiotics

35. Antimicrobial therapy
• General Principles
– Successful eradication by antimicrobials
– Bactericidal regimes should be used
– Combinations preferred to monotherapy
• Synergistic drugs enable bactericidal concentrations and may
shorten duration of Rx
– Duration
• PVE – atleast 6 weeks
• NVE – 2-6 weeks
– Organism
• Eg. Enterococci - 6 weeks

36. – For acutely ill patients with signs and symptoms
strongly suggestive of IE, empirical therapy may be
necessary
– The choice should take into consideration the
most likely pathogens and generally empirical
therapy should cover staphylococci, streptococci
and enterococci

37. Empirical Antibiotic Treatment of Infective
Endocarditis
Regimen Dose and Route Duration,
wk
Native Valve:
Amp-Sulbactam
+Genta
or
Vanc+Genta+Cipro
12g/d IV/IM 4dose
3mg/kg/day in 2 or 3
doses
4-6weeks
Prosthetic Valve <12 mo:
Vanco
+Genta
+Rifa
30mg/kg/day in 2 doses
3mg/kg/day in 2 or 3
doses
1200mg/d PO in 2 doses
6 weeks
2 weeks
Prosthetic valve > 12 mo
Rx same as for Native
Valve

38. NVE - Highly Penicillin-Susceptible Viridans Group
Streptococci and Streptococcus bovis
Regimen Dose and Route Duration,
wk
Aq penG sod 12–18 million U/24
h IV
Cont/4-6 doses
4weeks
Ceftriaxone sodium 2 g/24 h IV/IM
1dose
4weeks
Cef/PenG+Gentamy
cin
Genta:3mg/kg 2weeks
Vancomycin HCL 30mg/kg:2 doses
40mg/kg:2doses
4weeks

39. NVE – Relatively Resistant Viridans Group Streptococci
and Streptococcus bovis to Penicillin
Regimen Dose and Route Duration,
wk
Aq penG sod
+Genta
12–18 million U/24
h IV
Cont/4-6 doses
4weeks
2weeks Genta
Ceftriaxone sodium
+Genta
2 g/24 h IV/IM
1dose
4weeks
2weeks Genta
Vancomycin HCL 30mg/kg:2 doses
40mg/kg:2doses
4weeks

40. NVE- Staph spp.
Regimen Dose and Route Duration,
wk
Methicillin-susceptible
(flu)cloxacillin or
oxacillin
+ Genta
12 g/24 h IV in 4–6
doses
3mg/kg/day in 2 or 3
doses
6weeks
3-5 days
Methicillin-resistant
strains/Allergy
Vancomycin
+ Genta
30mg/kg:2 doses
40mg/kg:2doses
6weeks
3-5 days

41. PVE - Highly Penicillin-Susceptible Viridans Group
Streptococci and Streptococcus bovis
Regimen Dose and Route Duration,
wk
Aq penG sod 24M U/24 h IV
Cont/4-6 doses
6weeks
Ceftriaxone sodium 2 g/24 h IV/IM
1dose
6weeks
±Gentamycin Genta:3mg/kg For first 2weeks
Vancomycin HCL 30mg/kg IV :2 doses
40mg/kg:2doses
6weeks

42. PVE - Relatively Penicillin-Susceptible Viridans
Group Streptococci and Streptococcus bovis
Regimen Dose and Route Duration,
wk
Aq penG sod
+Gentamycin
24M U/24 h IV
Cont/4-6 doses
6weeks
Ceftriaxone+Genta
mycin
2 g/24 h IV/IM
1dose
6weeks
2 weeks Genta
Vancomycin HCL 30mg/kg IV :2 doses
40mg/kg:2doses
6weeks

43. PVE – Staph spp.
Regimen Dose and Route Duration,
wk
Methicillin-susceptible
(Flu)cloxacillin
+Genta
+Rifampin
12 g/24 h IV in 4–6 doses
3mg/kg/day in 2 or 3 doses
1200mg/24h in 2 doses
≥6weeks
2 weeks
≥6 weeks
Methicillin-resistant
strains/Allergy
Vancomycin HCL
+Genta
+Rifampin
30mg/kg:2 doses
40mg/kg:2doses
3mg/kg/day in 2 or 3 doses
1200mg/24h in 2 doses
≥6weeks
2 weeks
≥6 weeks

44. NVE or PVE – Susceptible strains of
Enterococcus spp
Regimen Dose and Route Duration,
wk
Ampicillin sodium 12g/24 h IV in 6
doses
4-6weeks
PenG+Gentamycin 18-30MU/24 IV 6
doses
4-6weeks
Vancomycin
HCL+Genta
30mg/kg:2 doses
40mg/kg:2doses
6weeks

45. NVE or PVE – Enterococci Susceptible to
Penicillin, Streptomycin, and Vancomycin and
Resistant to Gentamicin
Regimen Dose and Route Duration,
wk
Ampicillin sodium 12g/24 h IV in 6
doses
4-6weeks
PenG+Streptomycin 18-30MU/24 IV 6
doses
4-6weeks
Vancomycin
HCL+Streptomycin
Streptomycin
15mg/kg 24h 2
doses
6weeks

46. NVE or PVE – Enterococci Susceptible to
Aminoglycosides and Vancomycin and Resistant
to Penicillins
Regimen Dose and Route Duration,
wk
Ampicillin-
Sulbact+Gent
12g/24 h IV in 6
doses
6weeks
Vancomycin
HCL+Genta
Same doses as
above
6weeks

47. NVE or PVE – Enterococci Caused by Strains Resistant to
Penicillin, Aminoglycoside, and Vancomycin
Regimen Dose and Route Duration,
wk
E.Faecium
Linezolid 1200mg/24 h IV 2
doses
8weeks
E. Fecalis
Imepen+Ampicillin
Ceft+Ampicillin
Imepen 2g/24 h 4
doses
Cef 4g/24h in 2
doses
8weeks

48. Therapy of Endocarditis Caused by HACEK
Regimen Dose and Route Duration,
wk
Ceftriaxone sodium 2g/24h IV/IM 1 dose 4weeks
Ampicillin-
Sulbactam
12 g/24 h IV in 4
doses
4weeks
Ciprofloxacin 800mg/24h in 2
doses
4weeks

49. Fungal endocarditis
• Amphotericin B 0.7-1mg/kg/d for 6 weeks
• + or – Azoles
• Caspofungin
• Surgical excision

50. Culture Negative IE
Pathogens Therapy Proposed Outcome
Brucella spp Doxy+Septrin+Rifam
pin
Titre <1:60
Coxiella burnetti (Q
fever)
Doxy+OhCQ or
Doxy/Quinolone
IgG <1:200
IgM <1:50
Bartonella spp Ceftriaxone or Ampi
Or
Doxy + Genta
Success expected in
>90%
Legionella Erythrom + Rifampin
or Quinolone
Unknown
Mycoplasma Newer FQ’s Unknown

51. Suitability for Outpatient antibiotic
therapy (OPAT) for Endocarditis
Phase Guidelines
Critical Phase (<2weeks) Complications during this phase
Inpatient Rx is preferred
Consider OPAT: oral strepto, patient
stable and no complications
Continuation Phase (> 2 weeks) Consider OPAT if medically stable
Do NOT consider OPAT if Heart
failure, concerning echo features,
neuro signs, renal insuff
Essential for OPAT success Educate patient and staff
Regular post discharge evaluation
Prefer Physicial directed model – not
home infusion model

52. Prophylaxis
• Only for
– Patients with the Highest risk
– Undergoing Highest risk procedures

53. • Patients with Highest risk
– Patients with a prosthetic valve or a prosthetic
material used for cardiac valve repair
– Patients with previous IE
– Patients with congenital heart disease (CHD), in
particular those with complex cyanotic heart
disease and those who have post-operative
palliative shunts, conduits, or other prostheses

54. • Highest Risk Procedures
– Procedures at risk involve the manipulation of the
gingival or periapical region of teeth or perforation
of the oral mucosa (including scaling and root
canal procedures)
No compelling evidence that bacteraemia
resulting from either respiratory tract
procedures, gastrointestinal or genitorurinary
procedures, dermatological or musculoskeletal
procedures causes IE

55. Recommended regime for Prophylaxis
Situation Regime Dose (30 to 60 mins
before procedure)
No Penicillin allergy Amoxy or Ampi 2g PO or IV
Penicillin allergy Clindamycin 600mg PO or IV

56. Complications
• Heart failure
• Uncontrolled infections
• Systemic embolism
• Neurological complications (CVE, TIA)
• Infectious aneurysms
• Splenic complications (splenic infarcts)
• Myocarditis, pericarditis, arrhythmia
• Musculoskeletal complications
• Acute renal failure
56

57. Conclusion
• Where do we stand?
– Increasing no of
• Cardiac surgeries
• Intra vascular accesses
– High no of IVDU
– Diagnostic Limitations
– Inadequate availability of drugs
– Poor affordability of drugs
– No therapeutic drug monitoring

58. Reference
• ESC guidelines for IE 2015
58