Transcript Infective Endocarditis

Infective Endocarditis:
Epidemiology, Diagnosis and
Management
Holger P. Salazar, MD, FACC
Stern Cardiovascular Foundation
No financial relation to disclose
Epidemiology of Infective Endocarditis
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
Valvular Involvement in Infective
Endocarditis
Valve
Percent of Cases
Mitral
28-45%
Aortic
5-36%
Aortic + Mitral
0-35%
Tricuspid
5%
Combined right and left 0-4%
Most Common Underlying Cardiac
Lesions In Infective Endocarditis
 Mitral valve prolapse
 Degenerative valvular
lesions
 Calcified mitral annulus
 Valve nodules
 Bicuspid Aortic Valve
 Prosthetic Valve
Risk of Infective Endocarditis for
Selected Groups
Risk Factor
Incidence*
Injection Drug Use
150-2000
Rheumatic heart disease
440
Bioprosthesis
383
Prior endocarditis
340-740
Mechanical prosthesis
308
VSD (Medical therapy)
220
*Cases per 105 patient-years
Classification of Infective Endocarditis
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
Two Flavors of Infective Endocarditis:
Native and Prosthetic Valves
Clinical Manifestations of Endocarditis
Infective Endocarditis:
Symptoms (%)
Fever
80
Stroke
20
Chills
40
Skin lesions
20
Weakness
40
Headache
20
Dyspnea
40
Achiness
20
Sweats
25
Chest pain
15
Weight loss
25
Altered mental
Malaise
25
status
10-15
Back pain
10
Native Valve Endocarditis:
Signs (%)
Fever
90
Retinal lesions
Murmur
85
Skin manifestations 18-50
New
Changing
3-5
5-10
Emboli
50+
Splenomegaly
20-57
Metastatic
infection
20
20
Petechiae
20-40
Splinters
15
Osler’s nodes
10-23
Janeway lesions
<10
Cutaneous Findings of Endocarditis
Osler’s nodes are small
Splinter hemorrhages
raised, swollen, painful
erythematous lesions
the size of a pea,
on pads of fingers or toes
Janeway lesions are nontender
macular lesions most
commonly involving the
palms and soles and are caused
by septic emboli
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
Microbiology of Endocarditis
Microbiology of Native Valve
Endocarditis
Organism
Percent of
Cases
Viridans streptococci
30-40%
Other streptococci
15-25%
Staphylococcus aureus
10-27%
Enterococcus species
5-18%
Gram negative bacilli
2-13%
Microbiology of Prosthetic-Valve
Endocarditis
Organism
Percentage of Cases
Early Onset
Late Onset (> 12 m)
Coagulase negative staph
30-35%
15%
Staphylococcus aureus
17-23%
20%
Gram negative bacilli
10%
5%
Streptococci
5-10%
33%
Fungi
10%
2%
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
Echocardiography and Diagnosis of
Endocarditis
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
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%
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
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
Duke Criteria for Diagnosis of
Endocarditis
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
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
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
Right Sided Endocarditis in Injection
Drug Users
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 penicillinsusceptible 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
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
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
AHA Guidelines for Treatment of
Endocarditis
Aortic Versus Mitral Valve
Endocarditis
Overall
incidence
Surgical
Patients
Aortic
~55%
~75%
Mitral
~85%
~40%
Pulmonary
Tricuspid
~1%
~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!
AHA Guidelines for Antibiotic Therapy in
Native Valve Endocarditis
Organism
Regimen
PCN-sensitive
PCN G 12-18 MI qd or
Ceftriaxone 2 g qd or
Ceftriaxone 2 g qd +
Gentamicin 3 mg/kg qd
or Vancomycin 1 g bid
4
4
2
PCN-insensitive PCN G 18 MI qd +
Gentamicin 1 mg/kg tid
or Vancomycin 1 g bid
4
2
4
Doses assume normal renal function
Weeks
4
AHA Guidelines for Antibiotic Therapy in
Native Valve Endocarditis
Organism
Regimen
Weeks
MSSA
Oxacillin or Nafcillin 2 g q4h
4-6
or Cefazolin 2 g tid
4-6
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
4-6
4-6
AHA Guidelines for Antibiotic Therapy in
Native Valve Endocarditis
Organism
Regimen
Weeks
Enterococci (VSE) PCN + Gentamicin or
Vancomycin + Gentamicin
as above
6
6
HACEK
4
4
4
Ceftriaxone 2 g qd or
Ampicillin 2 g q4h +
Gentamicin 1 mg/kg tid
Doses assume normal renal function
AHA Guidelines for Antibiotic Therapy in
Prosthetic Valve Endocarditis
Organism
Regimen
Weeks
MSSA or MSSE Oxacillin or Nafcillin 2 g q4h 6+
+ Gentamicin 1 mg/kg tid
2
+ 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
6+
2
6+
Steel: Often the Best Antimicrobial
Agent In Treating Infective Endocarditis
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”
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
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
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
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
Early Surgery Versus Conventional Treatment for IE
Kaplan–Meier Curves for Cumulative Probabilities of Death
and Composite End Point at 6 Months
Kang DH, et al: NEJM 2012; 366:2466
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;366:2466-2473.
Kang DH, et al: NEJM 2012; 366:2466
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
Aortic Root Endocarditis With
Vegetation and Fistula to Right Atrium
The infection penetrates through to the floor of the
Right atrium just about to destroy the A-V node
Ventricular Assist Device Associated
Endocarditis
LVAD and Endocarditis
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
Pacemaker Associated Endocarditis
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
Pacemaker-Associated Endocarditis
Prophylaxis to Prevent Endocarditis
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
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
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
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)
ACC/AHA Guidelines for Prevention of
Bacterial Endocarditis
 Oral: Amoxicillin 2g 30-60 min before oral procedure
 Unable to take PO: Ampicillin 2g IM or IV, or cefazolin or
ceftriaxome IV 1g IM or IV 30-60 min before procedure
 Allergic to PCN – oral: clindamycin 600mg,
azithromycin or clarithromycin 500mg 30-60 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