Infective Endocarditis

Question 1

List the types of endocarditis

Answer 1

• Classic Subacute bacterial endocarditis (SBE)
• Classic Acute bacterial endocarditis (ABE)
• Right-Sided endocarditis
• Prosthetic valve endocarditis (PVE)
• Pacemaker-associated endocarditis
• Healthcare-associated endocarditis
• Injection drug use-associated endocarditis
• Culture-negative endocarditis

Question 2

Subacute bacterial endocarditis

Answer 2

o Subactue illness (several weeks duration)
o Low-grade fever (90%)
o Generalized problems: weight loss, malaise, anorexia, night sweats
o Heart murmur in 85%
o Peripheral stigmata of endocarditis:
• Splinter hemorrhages of nail beds (15%)
• Petechiae in skin, conjunctiva, oral mucoas (20-40%)
• Osler’s nodes on pads of fingers and toes (10-20%)
• Janeways lesions on palms and soles (50%)
o Mycotic aneurysms in cerebral circulation (20%)
o Neurologic symptoms (20-40%)
o Most common cause: viridans strep, enterococci, other strep, Staph aureus

Question 3

Acute bacterial endocarditis

Answer 3

o High fever
o Toxic appearance
o Less likely to have audible murmur
o More likely to have embolic complications
o May have evidence of mechanical valve dysfunction (CHF)
o Much fewer immunologic complications and peripheral stigmata
o Most common cause: Staph aureus, group B strep, group A strep, pneumococcus, aerobic Gram-negative bacilli

Question 4

Right-Sided endocarditis

Answer 4

o May lead to pulmonary complications

Question 5

Prosthetic valve endocarditis (PVE)

Answer 5

o Indolent or acute presentation
o Classified based on time since valve replacement

Early PVE
• < 60 days since surgery
• Source = intraoperative contamination
• Organisms = coagulase-negative Staph, S. aureus, GNR, enterococci, candida

Late PVE
• > 60 days
• Source = bacteremia (like in native valve endocarditis)
• Organisms = viridans strep, coagulase-negative Staph, enterococci, S. aureus, other strep
• Pathogens are more “community” type

Question 6

Pacemaker-associated endocarditis

Answer 6

o Organisms: Staphylococci (Staph aureus and coagulase-negative)
o Often requires removal of device
o Can also occur with other devices (ex: implantable defibrillators)

Question 7

Healthcare-associated endocarditis

Answer 7

o Predisposing factors: IV catheters, central lines, hemodialysis catheters
o Lead to bacteremia, subsequent endocarditis
o Organisms: S. aureus, coagulase negative staph, candida

Question 8

Injection drug use-associated endocarditis

Answer 8

o Most = without underlying cardiac disease
o Tricuspid > aortic or mitral valves
o Organisms: S. aureus (including MRSA), pseudomonas aeruginosa, candida
o Right-sided IE has good prognosis to medical therapy

Question 9

Culture-negative endocarditis

Answer 9

Most common cause = recent antibiotic therapy
• Suppressed bacterial growth in blood culture systems
• Results in false negatives
• Important to get pre-antibiotic blood cultures

Also from fastidious organisms
• Hard to grow in lab
• Include anaerobes, HACEK, Brucella

Also from rare organisms
• Not show up in conventional blood cultures
• Need PCR or serology for diagnosis
• Includes: fungi (Histoplasma, Aspergillus), Ligionella, Mycoplasma, Rickettsia, Chlamydia

Protocol for culture negative result:
• Prolonged incubation
• Variety of serologies, PCRs, and cultures to look for rare organisms

Question 10

Name the common organisms that cause the different types of endocarditis

Answer 10

Streptococci:
Viridans Streptococci (S. mutans)
• Common cause of SBE
• Most common cause in children
• Dental source common (especially if produce dextran because adheres to NBTE)
S. bovis:
• Associated with increased risk of colon cancer
S. pneumoniae:
• Common cause of SBE
• Can be part of Osler’s triad (IE, meningitis, pneumonia)
o Others: group B or A, etc.

Enterococci
o	Common cause of SBE
o	Difficult to treat
o	Need combination antibiotic therapy 
o	Often come from GI tract, sometimes GU tract

Staph aureus
o	Common cause of ABE, PVE, healthcare-associated, injection drug use associated IE
o	Most common cause of IE in adults 
o	Attacks normal valves
o	Highly virulent 
o	Often has fulminant course 
o	Metatstatic complications in 40% of cases 
o	Non-addicts
•	Usually left-sided disease 
•	Mortality rates: 25-40%
o	Injection-drug associated IE:
•	Often involves tricuspid valve
•	High cure rates: >85%
•	Relatively short courses of therapy 

Coagulase negative Staphylococci
o Common cause of PVE and pacemaker-associated IE
o Unusual cause of community-acquired IE
o Typically low virulence, indolent pathogens
o Particular species = S. lugdunensis
• High incidence of valve destruction and metastatic infection
• Often requires surgery

Gram-negative bacilli
o Seen in PVE and injection drug associated IV
o Overall, cause less than 10% of all IE
o Commonly have valve destruction and CHF
o High mortality (60-80%)
o Most common enterobacteriaceae = Salmonella and Klebsiella
o High mortality with Pseudomonas aeruginosa
• Often needs early surgery

HACEK organisms
o Group of fastidious Gram-negative organisms
o Have prolonged (>2 weeks) incubation time
o Account for 5-10% of community acquired SBE
o Include:
• Haemophilus
• Actinobacillus
• Cardiobacterium
• Eikenella
• Kingella

Fungi
o Most common = candida species
o Associated with central venous catheter candidemia and PVE
o Generally poor cure rate with medical therapy
o Most cases require surgery

Question 11

Describe the portal of entry of endocarditis

Answer 11

• Dental: viridans streptococci
• GU: secondary to UTI; entrance for Enterococci or Gram-negative aerobes
• GI: enterococci or Streptococci from GI tract
o Streptococcus bovis = strong association with underlying colon cancer
• Skin: S. aureus and S. epidermidis
• IV catheters: Staphylococci and Candida

Question 12

Describe the risk factors of endocarditis

Answer 12

• Prosthetic cardiac valve
• Previous IE
• Certain congenital heart conditions
• Certain post-cardiac transplantation conditions

Question 13

Describe the pathophysiology of endocarditis

Answer 13

Predisposing cardiac condition
o Rheumatic heart disease
o Congenital heart disease (mitral valve prolapse, bicuspid aortic valve, VSD, PDA, aortic coarctation, tetralogy of Fallot, pulmonary stenosis)
o Degenerative valve disease with age
o Prosthetic valves
o NOTE: no predisposing cardiac condition with most cases of acute bacterial endocarditis

Alteration of valve surface
o Valve disease leads to turbulent flow → alteration of valve surface
o Fibrin and platelets deposit
o Forms sterile vegetation: nonbacterial thrombotic endocarditis (NBTE)

Transient bacteremia
o Organisms gain entry to bloodstream
o See abnormal valve structure

Fibrin and platelet deposition
o Strep and Staph = potent platelet aggregators
o Result = increased size of vegetations

Organism growth beneath vegetation surface
o Minimal phagocytic penetration into vegetation
o Result: large bacterial colony
o Bacteria shed from vegetation → continuous bacteremia

Stimulation of Humoral and Cellular Immune systems
o But: avascular vegetations and poor phagocytic penetration
o Result: stimulated host defense, but essentially out of action
o Clinically:
• Hypergammaglobinemia
• Splenomegaly
• Immune-complex formation (glomerulonephritis, Osler’s nodes)

Complications:
o	Emobolic
o	Bacetermic 
o	Immunologic
o	Cardiac

Question 14

Describe the common clinical presentations of endocarditis

Answer 14

Variable

Ranges:
o Indolent illness (low grade fever, weight loss, malaise, anorexia)
o Rapid onset fulminant illness (high grade fever, severe HF due to acute valve destruction)
• Host defenses do not play much of a role

Question 15

Describe the common complications of endocarditis

Answer 15

Cardiac complications
o	Valve destruction
o	Myocardial abscess
o	Fistula between chambers
o	Conduction abnormalities
o	CHF (leading cause of death in IE)
o	MI
o	Pericarditis 

Embolic complications (highest risk = mitral valve endocarditis and large vegetations) 
o	Stroke
o	Renal infarcts
o	Splenic infarcts
o	Petechiae
o	Janeway’s lesions (painless flat lesions on palms and soles)
o	Splinter hemorrhages (nailbeds)
o	Pulmonary emboli (from right-sided IE)
o	Roth’s spots (retinal hemorrhages) 

Bacteremic complications
o	Sepsis
o	Mycotic aneurysm 
•	Septic emboli destroy muscular layer of an artery → dilation and aneurysm
•	Risk of bleeding
•	Most commonly in cerebral circulation and distal extremities 
o	Meningitis 
o	Brain abscess
o	Renal abscess
o	Splenic abscess
o	Osteomyelitis (bone infection) 
o	Septic arthritis 

Immunologic complications
o	Glomerulonephritis 
o	Vasculitis 
o	Osler’s nodes (painful, red swollen lesions on pads of fingers and toes)
o	Arthralgia/myalgia

Question 16

Describe the key features that allow the diagnosis of endocarditis to be made

Answer 16

Clinical clues
Murmur 
•	Most pateints with IE have a murmur 
•	85% SBE
•	Less often with other forms
•	Newly discovered or changing murmur can be important, but is relatively rare finding 
Exam/history to determine portal of entry:
•	Odontogenic source
•	Recent dental procedure
•	Poor dentition 
•	GI tract
•	Bleeding, pain, diarrhea, change in bowl habits
•	GU tract
•	UTI symptoms, bleeding, procedures 
•	Skin and soft tissue
•	Cuts, boils, infections 

Laboratory 
Blood cultures to determine the cause 
•	Most important lab test 
•	3 sets should be obtained to avoid false negatives or positives 
•	95%-100% have one of two sets positive
•	2/3 of cases have all 3 sets positive 
Routine labs = nonspecific 
•	Anemia is common (70-90%)
•	Leukocytosis (25%)
•	High sedimentation rate (ESR) and CRP
•	Hematuria 
Immunologic tests 
•	Often abnormal
•	Postivie ANA, rheumatoid factor, RPR, decreased complement 
ECG
•	May show new AV block or dysrhythmia 
Echocardiography
o	Find the vegetation 
o	Transesophageal echocardiogram (TEE)
•	Better assessment than transthoracic (TTE)
o	Sensitivity for detecting vegetations:
•	TTE: 60-70%
•	TEE: 75-95%

OVERALL:
o	Diagnosis requires integration of clinical, laboratory, and echo data
o	Duke criteria
•	1 major criteria and 1 minor
•	3 minor criteria

Question 17

Describe the concepts that underlie the management and prevention of endocarditis

Answer 17

• Establish clinical diagnosis
• Establish microbiologic diagnosis (blood cultures)
• Use MIC data to ensure antimicrobial susceptibility
Select antibiotic regimen:
o Bactericidal
o High-dose (to get high serum concentrations)
o Prolonged duration (weeks)
o Synergistic combinations when appropriate (Ex: penicillin and gentamicin for enterococcus)
• Monitor cardiac function, hemodynamics, renal, CNS, and vascular status
• Daily exam (in acute care hospital setting) = look for emboli and CHF
• Repeat blood cultures (make sure bloodstream has cleared)
• Search for portal of entry

Surgical therapy major indications:
o	CHF
o	Emboli
o	Resistant organisms
o	Uncontrolled infections
o	Prosthetic valve endocarditis 
o	Note: Do not delay surgery to sterilize valve first (persistent infection in new valve is uncommon) 

Prevention:
o Antibiotic prophylaxis before dental procedures, respiratory tract and other procedures with high risk cardiac conditions