1. Infective Endocarditis: Epidemiology, Diagnosis and Management Holger P. Salazar, MD, FACC Stern Cardiovascular Foundation No financial relation to disclose

2. Epidemiology of Infective Endocarditis

3. Epidemiology of Infective Endocarditis
Annual incidence in USA 10,000-20,000 new cases, stable over past 30 years
Prosthetic valve endocarditis accounts for 15% of cases
Mortality is about 20%, due to CHF, valvular dysfunction, or uncontrolled infection
50% over the age of 50

4. Valvular Involvement in Infective Endocarditis
Valve Percent of Cases
Mitral %
Aortic %
Aortic + Mitral %
Tricuspid %
Combined right and left %

5. Most Common Underlying Cardiac Lesions In Infective Endocarditis
Mitral valve prolapse
Degenerative valvular lesions
Calcified mitral annulus
Valve nodules
Bicuspid Aortic Valve
Prosthetic Valve

6. Risk of Infective Endocarditis for Selected Groups
Risk Factor Incidence*
Injection Drug Use
Rheumatic heart disease 440
Bioprosthesis
Prior endocarditis
Mechanical prosthesis
VSD (Medical therapy)
*Cases per 105 patient-years

7. Classification of Infective Endocarditis

8. Infective Endocarditis: Classification
Native Valve (75-90% of cases)
Acute -- ˃ 1 to 2 weeks
Subacute-- >2 week
Prosthetic Valve (10-25% of cases)
Early Onset-- ˃ 12 months
Late Onset-- > 12 months

9. Two Flavors of Infective Endocarditis: Native and Prosthetic Valves

10. Clinical Manifestations of Endocarditis

11. Infective Endocarditis: Symptoms (%)
Fever 80
Chills 40
Weakness 40
Dyspnea 40
Sweats 25
Weight loss 25
Malaise 25
Stroke 20
Skin lesions 20
Headache 20
Achiness 20
Chest pain 15
Altered mental
status 10-15
Back pain 10

12. Native Valve Endocarditis: Signs (%)
Fever 90
Murmur New Changing
Emboli 50+
Splenomegaly
Metastatic 20 infection
Retinal lesions
Skin manifestations 18-50
Petechiae
Splinters
Osler’s nodes
Janeway lesions <10

13. Cutaneous Findings of Endocarditis
Janeway lesions are nontender
macular lesions most
commonly involving the
palms and soles and are caused
by septic emboli
Osler’s nodes are small
raised, swollen, painful
erythematous lesions
the size of a pea,
on pads of fingers or toes
Splinter hemorrhages

14. Roth’s Spots and Endocarditis
Round or oval retinal
hemorrhages with white
spots seen in the retina
early in the course of IE,
caused by complex
mediated vasculitis

15. Microbiology of Endocarditis

16. Microbiology of Native Valve Endocarditis
Organism Percent of Cases
Viridans streptococci %
Other streptococci %
Staphylococcus aureus %
Enterococcus species %
Gram negative bacilli %

17. Microbiology of Prosthetic-Valve Endocarditis
Organism Percentage of Cases Early Onset Late Onset (> 12 m)
Coagulase negative staph 30-35% 15%
Staphylococcus aureus % 20%
Gram negative bacilli 10% 5%
Streptococci % 33%
Fungi 10% 2%

18. Causes of Culture-Negative Endocarditis
Coxiella burnetti (Q fever)
Bartonella species (cat scratch disease)
HACEK organisms*
Legionella species
Aspergillus species
Lactobacillus species
* Haemophilus species; Actinobacillus actinomycetemcomitans;
Cardiobacteriumhominis; Eikenella corrodens; and Kingella kingae

19. Echocardiography and Diagnosis of Endocarditis

20. Transthoracic Echocardiography and Endocarditis
No technological advance has had as much impact on approach to patients with IE
Rapid, non-invasive and specific for vegetations (98%)
May be inadequate in 20% of patients because of obesity, COPD, or chest-wall deformities
TTE should be used in the evaluation of those with suspected native valve IE who are good candidates for imaging

21. Transesophageal Echocardiography and Endocarditis
More costly and invasive but increases the sensitivty (from 75% to 95%) while maintaining specificity (85-98%)
More sensitive for defining perivalvular extension, perforation of valves, and myocardial abscess
A negative TEE has a negative predictive value for IE of > 92%

22. TTE or TEE or Both?
Recent guidelines suggest that among patients with suspected endocarditis appropriate use of echocardiography depends on prior probability of IE
If this probability is < 4% , a negative TTE is cost effective and satisfactory in ruling out IE
If this probability is 4 to 60%, initial use of TEE is more cost effective and efficient than initial TTE followed by TEE (if former negative)
Mylonakis & Calderwood NEJM 2001;345:1318

23. Limitations of Echocardiography in the Diagnosis of Endocarditis
Falsely negative early in disease
False positive diagnosis with thickened valve leaflets, valve nodules or tumors
Inability to distinguish healed from active vegetations
Lower sensitivity in those with mechanical prostheses
Blood cultures remain the test of choice for patients with suspected endocarditis

24. Duke Criteria for Diagnosis of Endocarditis

25. Duke Criteria for Diagnosis of Infective Endocarditis: Major Criteria
Positive blood culture for typical organism (from 2 separate cultures or Staphylococcus aureus or enterococcal bacteremia without a primary focus) or
Persistent bacteremia for any organism > 12 hrs apart or
All of 3 or majority of 4 BC positive drawn > 1 hr apart
Echocardiographic criteria
- Oscillating mass, abscess or new dehiscence of prosthesis
- New valvular regurgitation

26. Duke Criteria for Diagnosis of Infective Endocarditis: Minor Criteria
Predisposing heart condition or injection drug use
Fever greater than or equal to 38o C
Immunologic phenomena: GN, Osler’s nodes, Roth Spots, RF
Echo consistent, but not meeting major criteria
Vascular phenomena: arterial embolism, septic PE, mycotic aneurysm, intracranial hemorrhage, Janeway lesions
Microbiologic evidence: positive BC not meeting major criteria or serology indicating active infection with consistent organism

27. Duke Criteria for Diagnosis of Infective Endocarditis
Definite endocarditis: Pathologic criteria
Organisms by culture or histology in vegetation, embolus, or cardiac abscess or
Pathologic lesion such as vegetation or cardiac abscess
Clinical criteria
2 major, or 1 major plus 3 minor, or 5 minor criteria

28. Right Sided Endocarditis in Injection Drug Users

29. Right-sided Endocarditis in Injection Drug Users
46 y/o man injection drug user (heroin)
with fevers, sweats and right sided pleuritic
chest pain. Blood cultures grew penicillin-
susceptible S. aureus and echocardiogram
showed 1 mm Tricuspid valve vegetation.
HIV negative and in hospital for 7 days
with oxacillin and gentamicin followed by
21 days of outpatient ceftriaxone (2 gms/
day).
Multiple peripheral septic emboli with cavitation

30. Right-Sided Endocarditis in Injection Drug Users
Common complication with overall favorable prognosis
Vegetations > 2 cm associated with higher mortality (33% vs 1.3%)
S. aureus most common pathogen (>80%) than Viridans streptococci
>50% with septic emboli on chest radiographs
Hecht SR and Berger M Ann Int Med 1992;117:560

31. Right Sided Endocarditis in Injection Drug Users: Treatment
Two week regimen (nafcillin or oxacillin + gentamicin) for susceptible isolates
Oral therapies still controversial
Exclusion to “short-course” protocol:
Extracardiac complications of IE
Fever for > 7 days
HIV infection
Vegetation > 1-2 cm
Chambers HF Ann Intern Med 1988;109:619

32. AHA Guidelines for Treatment of Endocarditis

33. Aortic Versus Mitral Valve Endocarditis
Overall incidence
Surgical Patients
Aortic ~55% ~75%
Mitral ~85% ~40%
Pulmonary ~1%
Tricuspid ~20%
Acute aortic regurgitation is poorly tolerated because the LV is less compliant than the LA resulting higher LV wall stress! Watch out for abrupt deterioration!

34. AHA Guidelines for Antibiotic Therapy in Native Valve Endocarditis
Organism Regimen Weeks
PCN-sensitive PCN G MI qd or 4 Ceftriaxone 2 g qd or Ceftriaxone 2 g qd Gentamicin 3 mg/kg qd or Vancomycin 1 g bid 4
PCN-insensitive PCN G 18 MI qd Gentamicin 1 mg/kg tid 2 or Vancomycin 1 g bid 4
Doses assume normal renal function

35. AHA Guidelines for Antibiotic Therapy in Native Valve Endocarditis
Organism Regimen Weeks
MSSA Oxacillin or Nafcillin 2 g q4h or Cefazolin 2 g tid both +/- Gentamicin 1 mg/kg tid 3-5d
or Vancomycin 1 g bid +/- Gent
MRSA Vancomycin 1 g bid /- Gentamicin 1 mg/kg tid Doses assume normal renal function

36. AHA Guidelines for Antibiotic Therapy in Native Valve Endocarditis
Organism Regimen Weeks
Enterococci (VSE) PCN + Gentamicin or Vancomycin + Gentamicin as above
HACEK Ceftriaxone 2 g qd or Ampicillin 2 g q4h Gentamicin 1 mg/kg tid 4
Doses assume normal renal function

37. AHA Guidelines for Antibiotic Therapy in Prosthetic Valve Endocarditis
Organism Regimen Weeks
MSSA or MSSE Oxacillin or Nafcillin 2 g q4h Gentamicin 1 mg/kg tid Rifampin 300 mg tid 6+
MRSA or MRSE Vancomycin 1 g bid Gentamicin 1 mg/kg tid Rifampin 300 mg tid Doses assume normal renal function

38. Steel: Often the Best Antimicrobial Agent In Treating Infective Endocarditis

39. Medical versus Surgical therapy
Surgery is always in addition to medical therapy
The vast majority of the operated patients would die if not operated
Some medically treated patients are “inoperable”

40. Surgical Indications in Endocarditis
Refractory CHF
> 1 serious embolic event
Uncontrolled infection
Physiologically significant valve dysfunction by echo
Fungal endocarditis
Ineffective antimicrobial therapy
Mycotic aneurysm
Most cases of PVE due to antibiotic resistant pathogens
Local cardiac suppurative complications

41. Echocardiographic Features Predicting Need for Surgery in Endocarditis
Persistent vegetations after a major embolus
Large (> 1 cm) mitral valve vegetation
Increasing vegetation size after 4 weeks of antimicrobial therapy
Acute mitral insufficiency
Valve perforation or rupture
Periannular extension of infection
AHA Committee on Endocarditis

42. Homograft or Prosthetic Valve Replacement for Aortic Valve IE
There are no and probably will be no randomized studies!
Good results are possible to obtain with either
However, an increasing number of publications favor homografts
Technically easier and safer
Lower risk of heart block
Lower infection and re-infection rate
Homograft does not require anticoagulation
Limited supply of homografts
Limited durability of homograft

43. Timing of Surgery 30% require surgery in the acute phase
another 20-40% will require surgery later
Main principle: Don’t postpone an indicated operation, however:
Pts with strokes: Postpone surgery, if possible 1-3 weeks, particularly if evidence of hemorrhage
If valve repair is planned: 1 week of preop antibiotic treatment
Re-infection rate is lower after surgery for healed endocarditis

44. Early Surgery Versus Conventional Treatment for IE
Kaplan–Meier Curves for Cumulative Probabilities of Death and Composite End Point at 6 Months
Figure 2. Kaplan–Meier Curves for the Cumulative Probabilities of Death and of the Composite End Point at 6 Months, According to Treatment Group. There was no significant between-group difference in all-cause mortality at 6 months (Panel A). The rate of the composite end point of death from any cause, embolic events, recurrence of infective endocarditis, or repeat hospitalization due to the development of congestive heart failure was 3% in the early-surgery group versus 28% in the conventional-treatment group (hazard ratio, 0.08; 95% CI, 0.01 to 0.65; P=0.02) (Panel B).
Kang DH, et al: NEJM 2012; 366:2466

45. Early Surgery Versus Conventional Treatment for IE Clinical End Points
Early Surgery Versus Conventional Treatment for Infective Endocarditis
Kang D et al. N Engl J Med 2012;366:
Kang DH, et al: NEJM 2012; 366:2466

46. Special Surgical Considerations Related to Location
Aortic valve IE: Be aggressive!
Acute aortic regurgitation is poorly tolerated
Mitral valve IE: Repair whenever possible, consider risk of embolism
Right-sided IE: Be conservative!
Repair, excision, (replacement)
Pulmonary valve IE is very uncommon

47. Aortic Root Endocarditis With Vegetation and Fistula to Right Atrium

48. The infection penetrates through to the floor of the
Right atrium just about to destroy the A-V node

49. Ventricular Assist Device Associated Endocarditis

50. LVAD and Endocarditis

51. Endocarditis and Ventricular Assist Devices
Patients with VADs are at high risk for nosocomial bloodstream infections
Incidence of VAD associated IE may be as high as 13% (relapsing bacteremia/fungemia common)
At least 24 cases in literature (33% Candida 20% Enterococcus) with 50% associated mortality
Difficult to visualize inflow and outflow conduits by echocardiography
Treatment: tranplantation! Device exchange high rate of failure/death
Gordon and McCarthy in Advanced Therapy Cardiac Surgery 2002

52. Pacemaker Associated Endocarditis

53. Pacemaker-Associated Endocarditis
>2 million people (including 1 million Americans) use pacemakers
Infections uncommon but difficult to eradicate without device removal (generator + leads via laser extraction if possible)
Pacemaker endocarditis can be difficult diagnosis to make on clinical grounds
TEE sensitive in finding suspicious lesions on pacemaker
Chua J et al Ann Int Med 2000;133:644

54. Pacemaker-Associated Endocarditis

55. Prophylaxis to Prevent Endocarditis

56. Endocarditis Prophylaxis
Class I: No class I indications.
Class IIa: Reasonable for pts at highest risk for adverse outcomes from IE having dental procedures that involve manipulation of either gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
- Pts with prosthetic cardiac valves or prosthetic
material used for valve repair
- Pts with previous IE
- Pts with CHD: unrepaired cianotic CHD including
paliative shunts and conduits
ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676

57. Endocarditis Prophylaxis
Class IIa (cont):
- Complete repaired CHD fixed with prosthetic material
or device, whether placed surgically or by catheter
intervention, during first 6 months after procedure
- Repaired CHD with residual defects at the site or
adjacent to the site of a prosthetic patch or device
- Cardiac transplant pts with valve regurgitation due
to structurally abnormal valve
Class III: Prophylaxis not recommended against nondental procedures: TEE, EGD or colonoscopy
ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676

58. Endocarditis Prophylaxis
Prophylaxis accepted in high risk pts:
- Incision of the respiratory tract mucosa, such
as tonsillectomy and adenoidectomy
- Infections of the GI or GU tract
- Pts undergoing elective cistoscopy or other
urinary tract manipulation who have
enterococcal UTI
ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676

59. Procedures Not Requiring Prophylaxis in At Risk Patients
Dental restoration
Adjustment of braces
Flexible bronchoscopy
GI endoscopy
C-section deliveries
Cardiac catheterization
Urethral catheterization (sterile urine)

60. ACC/AHA Guidelines for Prevention of Bacterial Endocarditis
Oral: Amoxicillin 2g min before oral procedure
Unable to take PO: Ampicillin 2g IM or IV, or cefazolin or
ceftriaxome IV 1g IM or IV min before procedure
Allergic to PCN – oral: clindamycin 600mg,
azithromycin or clarithromycin 500mg min before
procedure
Allergic to PCN and unable to take PO: clindamycin 600mg IM or IV or cefazolin or ceftriaxone 1g IM or IV (do not use if anaphylaxis, angioedema, urticaria with PCN
ACC/AHA 2008 Guideline Update on Valvular Heart Disease: JACC 2008; 676