Infective

Endocarditis
Amir Eslami, DO
Learning Objectives
• Overview
• Risk factors
• Pathophysiology
• Clinical Presentation
• Diagnosis Criteria
• Treatment overview
• High-risk patients
• Complications
• Indications for surgery 
• Prophylaxis
Overview
Acute Disease Subacute Disease
• High fevers • Slower and more
• Elevated WBC counts subtle presentation
• Systemic toxicity • Low-grade fevers
• Night sweats
Fulminant, usually presents • Fatigue
with rapidly progressive
symptoms with complications Can be vague. Sometimes
of endocarditis such as acute with constitutional symptoms
heart failure or embolic or occasional fevers or chills.
events or heart block Or just unwell feelings. Or
none!
Risk Factors
• Presence of a prosthetic • Healthcare-related exposure
valve (highest risk) • Dental disease and manipulation
• Extracardiac infection, lungs, UTI, skin, bone
• Previous endocarditis • Instrumentation for other procedures
(highest risk)
• Acquired valvular
• Congenital heart disease dysfunction
(CHD)
• Cardiac implantable devices
• Chronic IV access
• Chronic heart failure
• Diabetes mellitus
• Mitral valve prolapse with
regurgitation
• IV drug abuse
Where and what valves?
• Any endocardial surface infection more valve
involvement
• 38% aortic valve, 34% mitral valve, 8% both aortic
and mitral valves, 4% tricuspid valve
• Congenital heart disease: 3.5%
• Rare in PS, MS, ASD, HCM

• More virulent pathogens can affect normal valves

• Abnormal valves are prone to infective endocarditis
Pathophysiology
• Hematogenous spread is the most common
pathway
• Endothelial surface of the heart must be damaged
• Platelet and fibrin depositions occur on the damaged
epithelial surface
• Bacteremia gives organisms access to and results in
colonization of the endocardial surface
• After the colonization of the endothelial surface, a
“vegetation” of fibrin, platelets, and bacteria forms
• Implantation of prosthetic values or other cardiac
hardware that has been contaminated with
pathogens is another pathway for endocarditis
Most Common Pathogens
Agent Percentage of Cases
Staphylococci 30–70
•Coagulase positive 20–68
•Coagulase negative 3–26
Streptococci 9–38
Streptococcus Bovis endocarditis is often
•Viridans streptococci associated with malignancy of the 10–28
•Other streptococci gastrointestinal tract. 3–14
Enterococci 5–18
Gram-negative aerobic bacilli 1.5–13
Fungi 1–9
Miscellaneous bacteria <5
Mixed infections 1–2
“Culture negative” <5–17
Clinical Presentation
Symptoms Signs
• Chills • Fever
• Night Sweats • Shock
• Weakness • New or changing heart
• Dyspnea murmur
• Weight Loss • Embolic Phenomena
• Myalgia or arthralgia • Skin manifestations
• Janeway lesions (septic emboli, painless)
• Constitutional symptoms • Osler’s nodes (immune complexes; painful)
• Splinter hemorrhages (septic emboli)
• More in subacute** • Roth spot (retinal hemorrhages)

• Clubbing of extremities
Clinical Presentation
Laboratory Tests Diagnostic Tests
• WBC count normal or elevated • Electrocardiogram
• Anemia • Chest radiograph
• Elevated C-reactive protein • Echocardiogram
(CRP) • Transthoracic (TTE)
• Elevated erythrocyte • Transesophogeal (TEE)
sedimentation rate (ESR)
• Blood Cultures
Clinical Presentation
• The signs and symptoms of infective endocarditis are
not specific, and the diagnosis is often unclear
• The Duke Criteria integrate clinical, laboratory, and
echocardiographic findings to identify the likelihood a
patient has endocarditis
• Patients are grouped into one of three categories
• Definite infective endocarditis
• Possible infective endocarditis
• Infective endocarditis rejected
Modified Duke Criteria:
• Definite Infective Endocarditis
• Pathological criteria
• Microorganisms demonstrated by culture or histological
examination of a vegetation, a vegetation that has embolized, or an
intracardiac abscess specimen
• Pathological lesions; vegetation or intracardiac abscess confirmed by
histological examination showing active endocarditis
• Clinical criteria
• 2 major criteria
• 1 major criterion and 3 minor criteria
• 5 minor criteria
Modified Duke Criteria:
• Possible IE
• 1 major criterion and 1 minor criterion
• 3 minor criteria
• Rejected
• Firm alternative diagnosis explaining evidence of IE; or
• Resolution of IE syndrome with antibiotic therapy for 4 days; or
• No pathological evidence of IE at surgery or autopsy, with antibiotic
therapy for 4 days; or
• Does not meet criteria for possible IE as above
Treatment Overview
• Empiric antibiotic treatment until an infecting pathogen is isolated
• High dose, parenteral, bactericidal pathogen-specific antibiotics
for an extended period
• A minimum of 4 to 6 weeks of antibiotic therapy is generally
required
• β-Lactam antibiotics, such as penicillin G (or ceftriaxone), nafcillin,
and ampicillin, remain the drugs of choice
• The use of synergistic antimicrobial combinations may be required
for certain pathogens to obtain a bactericidal effect
• Once the infecting pathogen is identified, there are detailed
guidelines for the treatment of each specific bacteria
Native Valve Endocarditis caused by highly penicillin- susceptible
(MIC≤ 0.12 mcg/mL) viridans group streptococci and Streptococcus
gallolyticus (bovis)
Regimen Duration Adult Dose
(weeks)
Aqueous crystalline penicillin G sodium 4 12-18 million units/24 hours

Ceftriaxone 4 2 grams/24 hours

Vancomycin 4 Trough goal 10-15

Aqueous crystalline penicillin G sodium 2 12-18 million units/24 hours

plus
Gentamicin (traditional dosing peak of 3-4 mcg/ml)
Ceftriaxone 2 2 grams/24 hours
plus
Gentamicin (traditional dosing peak of 3-4 mcg/ml)
Native Valve Endocarditis caused by Streptococcus
gallolyticus (bovis) and viridans group streptococci
relatively resistant to penicillin (MIC> 0.12 mcg/mL)

Regimen Duration Adult Dose

(weeks)
Aqueous crystalline penicillin G sodium 4 24 million units/24 hours

Plus
Gentamicin (traditional dosing peak of 3-4 mcg/ml) 2

Vancomycin 4 Trough goal 10-15

Prosthetic Valve Endocarditis caused by highly penicillin- susceptible (MIC≤ 0.12
mcg/mL) viridans group streptococci and Streptococcus gallolyticus (bovis)
Regimen Duration Adult Dose
(weeks)
Aqueous crystalline penicillin G sodium 6 12-18 million units/24 hours

Ceftriaxone 6 2 grams/24 hours

Vancomycin 6 Trough goal 10-15

Aqueous crystalline penicillin G sodium 6 12-18 million units/24 hours

plus
Gentamicin (traditional dosing peak of 3-4 mcg/ml) 2

Ceftriaxone 6 2 grams/24 hours

plus
Gentamicin (traditional dosing peak of 3-4 mcg/ml) 2
Prosthetic Valve Endocarditis caused by Streptococcus
gallolyticus (bovis) and viridans group streptococci
relatively resistant to penicillin (MIC> 0.12 mcg/mL)
Regimen Duration Adult Dose
(weeks)
Aqueous crystalline penicillin G sodium 6 24 million units/24 hours

Plus
Gentamicin (traditional dosing peak of 3-4 mcg/ml) 2

Ceftriaxone 6 2 grams/24 hours

Plus
Gentamicin (traditional dosing peak of 3-4 mcg/ml) 2

Vancomycin 4 Trough goal 10-15

Native Valve Endocarditis caused by Staphylococci
Regimen Duration Adult Dose
(weeks)
MSSA
Oxacillin or Nafcillin 6 12g/24 hours

Cefazolin 6 6 gm/24 hours

MRSA
Vancomycin 6 Trough goal 10-20

Daptomycin 6 ≥ 8 mg/kg/dose
Prosthetic Valve Endocarditis caused by Staphylococci
Regimen Duration Adult Dose
(weeks)
MSSA
Oxacillin or Nafcillin 6+ 12g/24 hours
Plus Rifampin 6+ 900 mg/24 hours
Plus gentamicin 2 Traditional dosing Peak goal
3-4 mcg/ml

MRSA
Vancomycin 6+ Trough goal 10-20
Plus Rifampin 6+ 900 mg/24 hours
Plus gentamicin 2 Traditional dosing Peak goal
3-4 mcg/ml
 Prosthetic or Native Valve Endocarditis caused by Enterococci
Regimen Duration Adult Dose
(weeks)
Ampicillin 4-6 12g/24 hours
Plus gentamicin 4-6 Traditional dosing Peak goal 3-4 mcg/ml

OR
Aqueous crystalline penicillin G sodium 4-6 18-30 million units/24 hours
Plus gentamicin 4-6 Traditional dosing Peak goal 3-4 mcg/ml
OR

Ampicillin 4-6 12g/24 hours

Plus Ceftriaxone 4-6 2 gm IV Q 12H
OR
Vancomycin 4-6 Trough goal 10-15
Plus gentamicin 4-6 Traditional dosing Peak goal 3-4 mcg/ml
Native and Prosthetic Valve Endocarditis caused by
HACEK Microorganisms
Regimen Duration Adult Dose
(weeks)
Ceftriaxone 4-6 12g/24 hours

Ampicillin 4-6 6 gm/24 hours

Ciprofloxacin 4-6 400 mg IV Q12H

Endocarditis Culture Negative
Therapies
• A patient with an acute clinical presentation of native
valve infection should be started on antibiotic coverage
for S aureus, β-hemolytic streptococci, and aerobic
Gram-negative bacilli
• A patient with a subacute clinical presentation of native
valve infection should be started on antibiotic coverage
for S aureus, viridans group streptococci, HACEK, and
enterococci
Monitoring of Infective Endocarditis
• Fever usually subsides within 1 week of initiating
therapy
• Echocardiography should be completed after completion
of antibiotic therapy to establish a new baseline heart
function
• Blood cultures should be negative within a few days of
starting antibiotic therapy
Highest Risk Patients for
Endocarditis
• Prosthetic cardiac valve or prosthetic material used for cardiac valve
repair
• Previous infective endocarditis
• Congenital heart disease (CHD)
• Unrepaired cyanotic CHD, including palliative shunts and conduits
• Completely repaired congenital heart defect with prosthetic material or device,
whether placed by surgery or by catheter intervention, during the first 6
months after the procedure
• Repaired CHD with residual defects at the site or adjacent to the site of a
prosthetic patch or prosthetic device (which inhibits endothelialization)
• Cardiac transplantation recipients who develop cardiac valvulopathy
Complications
• Heart failure
• Sudden significant valve regurgitation due to
• Perforated leaflet of the native valve or bioprosthetic valve
• Chordal rupture
• Prosthetic valve dehiscence
• Fistula creating a shunt
• Bulky vegetation obstructing a valve (rarely)

• IE progressing to CHF occurs most frequently in aortic valve infections, and

CHF due to acute aortic regurgitation is poorly tolerated
• Afterload reduction (nitrates/nitroprusside)
CHF is the most common
indication for early surgery in IE
• (Class I indication)
• Medical therapy to surgical intervention in patients with IE and CHF
showed a clear superiority with surgery; surgical treatment was
associated with a 23% mortality rate, compared with a 71% mortality
rate with medical therapy
• Elevated left ventricular diastolic pressure (including premature mitral
valve closure in acute aortic regurgitation) should prompt the decision
for urgent surgery
Surgical Indication
Recap surgical intervention…one
more time!
• Fungal and many cases of staphylococcal and gram-negative endocarditis,
whether NVE or PVE, almost always require surgical intervention.
• Class I indications for surgery include
• Valve dysfunction causing heart failure
• Resistant organism (e.g., fungi)
• Heart block or abscess
• Persistent infection (positive surveillance cultures)
• Relapsing PVE
• Early valve surgery has been reported to be beneficial in terms of survival
and prognosis, despite a slight increase in early postoperative mortality.
 Prophylaxis of Infective Endocarditis
Highest Risk Cardiac Conditions Presence of a prosthetic heart valve
Prior diagnosis of infective endocarditis
Cardiac transplantation with subsequent valvulopathy
Congenital heart disease (CHD)
Types of procedures Any that requires perforation of the oral mucosa or manipulation of the periapical region of the
teeth of gingival tissue

Antimicrobial Options Adult Doses Pediatric Doses (mg/kg)

Oral amoxicillin 2g 50
IM or IV ampicillinc 2g 50
IM or IV cefazolin or ceftriaxonec,d,e 1g 50
Oral cephalexind,e,f 2g 50
Oral clindamycine 600 mg 20
Oral azithromycin or clarithromycine 500 mg 15
IV or IM clindamycinc,e 600 mg 20
Summary
• Endocarditis typically presents as fever and toxic
appearance
• Early recognition and treatment are critical
• Antibiotic treatment durations differ when treating
native vs. prosthetic valve infections
• There are specific guidelines for each pathogen causing
endocarditis – talk to your friendly ID and pharmacist
• Patients at the highest risk of infective endocarditis
should receive prophylactic antibiotic therapy
• Any questions?