PHAR 255 - Endocarditis

Question 1

What is Endocarditis?

Answer 1

Infection of the heart valves and other heart tissues
- More often seen in older adults (>50yo) and PWID
- Can occur, but Uncommon in pediatrics

Question 2

What is the Endocardium?

Answer 2

Membrane that lines the chambers of the heart and covers the valves

Question 3

Pathophysiology of Endocarditis

Answer 3

Altered endocardial surface produces a suitable site for bacterial attachment and colonization (trauma, turbulence, previously damage valve) → Formation of platelt-fibrin thrombus on the altered surface (non-bacterial thrombotic endocarditis) → Bacteremia (hematogenous spread and then bacteria adheres and colonizes on the heart) → Formation of vegetation of fibrin, platelts, and bacteria

Question 4

Endocarditis Classifications:

Native Valve Endocarditis (NVE)

Answer 4

Infection of a non-prosthetic heart valve (i.e. original heart valve)

Question 5

Endocarditis Classifications:

Prosthetic Valve Endocarditis (PVE)

Answer 5

Infection of a heart valve that has been replaced (mechanical or bioprosthetic)
- Most severe form of infective endocarditis
- May be more common in bioprosthetic than mechanical valve replacement

Question 6

Endocarditis Classifications:

2 Subclassifications of PVE

Answer 6

Early Onset → within 1 year of surgery
- Organisms introduced at time of surgery
- Usually staphylococcal (S. aureus and S. epidermidis) but also may be gram-negative bacilli or fungal (nosocomial bugs)

Late Onset → 1 year after surgery
- Same organisms as NVE

Question 7

Endocarditis Classifications:

Left-Sided Endocarditis

Answer 7

Mitral and Aortic valves
- More common

Question 8

Endocarditis Classifications:

Right-Sided Endocarditis

Answer 8

Pulmonary and Tricuspid Valves
- Less common
- PWID, immunocompromised

Question 9

Cardiac Risk Factors For Developing Endocarditis

Answer 9

• Previous infective endocarditis
• Valvular heart disease
• Prosthetic heart valve
• Central venous or arterial catheter
• Implanted cardiac device
• Congenital heart disease

Question 10

Non-Cardiac Risk Factors For Developing Endocarditis

Answer 10

• Central venous catheter
• PWID
• Immunosuppression
• Recent dental or surgical procedure
• Recent hispitalization
• Hemodialysis

Question 11

Etiology: Native Valve Endocarditis

Answer 11

• Staphylococcus aureus (skin)
• Viridans streptococci (oral cavity)
• Enterococcus species (gut/urinary tract)

Question 12

Etiology: Prosthetic Valve Endocarditis

Answer 12

• Staphylococcus aureus
• Coagulase negative staphylococcus (CONS, S. epidermis)
• Enterococcus
• Candida

Question 13

Non-Specific Signs and Symptoms of Endocarditis

Answer 13

• Fever 86-96% of cases (low grade fever may also present)
• Heart murmur (new or worsening of old)
• Fatigue, weakness, weight loss, arthralgia, myalgias, night sweats, headache
• Congestive heart failure

Question 14

Specific Signs and Symptoms of Endocarditis

Answer 14

Osler nodes → purple subcutaneous nodules on fingertips/toes, painful or tender, caused by immun complex deposition
Janeway lesions → eryhtmatous, nonpainful macules on palms and soles
Splinter hemorrhages → little hemorrhages in nail bed
Petechiae → small, red, painless hemorrhagic lesions
Vascular embolic event → complications from clots, end target organ damage

Question 15

Specific Signs and Symptoms of Endocarditis in PWID and IV Drug Use

Answer 15

• More often tricuspid valve involvement (right-sided endocarditis)
• If pulmonary valve involved it can lead to → Pulmonary syndrome (fever, cough, hemoptysis, pleuritic chest pain)

Question 16

Lab Markers for Endocarditis

Answer 16

• ↑ WBC
• ↑ ESR or CRP
• ↑ procalcitonin
• Normocytic, normochromic anemia
• Organ-specific blood work changes: creatinine, cardiac troponins, serum lactate

Question 17

Diagnosis:

Importance of Blood Cultures in Endocarditis and How it is Done

Answer 17

Imperative in the diagnosis and selection of therapy based on bacteria found
- If a patient is hemodynamically stable, blood cultures should be taken prior to antibiotic therapy
- Shedding of bacteria from the vegetation
- Samples from 3 sites (2 peripheral pokes (each arm) and if central line is present, one culture needs to be from this line as it could be the source of infection)

Question 18

Diagnosis:

Use of Echocardiography in Endocarditis and the 2 Types

Answer 18

Can visualize vegetation and see cardiac function and abnormalities (typically used for heart function)
1. Transthoracic (TTE)→ first step when endocarditis expected OR when patients have S. aureus bacteremia (sensitivity 60%)
2. Transesophageal (TEE) → more specific for visualizing vegetations (sensitivity 90%)

Question 19

What Criteria is Used to Diagnose Endocarditis?

Answer 19

Modified Duke Criteria

Question 20

Mortality and Complications of Endocarditis

Answer 20

In-hospital mortality rats are very high → 15-30%
Complications:
- recurrent IE
- Destruction of heart valves, fibrosis, and abscess formation
- Heart failure
- Cardiomyopathy
- Septic emboli
- Glomerulonephritis
- Stroke

Question 21

Goals of Therapy for Endocarditis

Answer 21

• Eradicate the organism ASAP
• Identify and manage the primary source of infection ASAP
• Relieve all signs and symptoms within 1 week
• Decrease morbiddity and mortality associated with IE
• Implement appropriate prophylactic antimicrobial regimens to prevent infective endocarditis in individuals at high risk

Question 22

Treatment Principles for Endocarditis

Answer 22

• Antimicrobials and Surgery (when needed) → eradicate organisms and remove infected material
• Bactericidal regimens are more effective than bacteriostatic therapy
• Antibiotic tolerance → some organisms escape drug-induced killing and can continue to grow after treatment is stopped (vegetations and biofilms require prolonged and combination therapy)

Question 23

Empiric Therapy for All Types of Endocarditis

Answer 23

Ceftriaxone + Vancomycin

Question 24

Pathogen Directed Therapy for Endocarditis:

Treatment Duration

Answer 24

4-6 weeks, except for gentamicin which is used only for first 2 weeks (synergy)
- Course duration starts from the first negative blood culture and prolonged if complications or patient requires surgery
- So a key monitoring parameter is serial blood cultures (usually every 2 days)

Question 25

Endocarditis and PWID

Answer 25

- More commonly right-sided endocarditis (tricuspid > pulmonary valve) - Repeat IV injections leads to contaminated particles causing infection - Mortality rates are usually low, despite requiring surgery - Increased rate of IE recurrence

Question 26

What is Gentamicin Synergy

Answer 26

Gentamicin is used in combination with beta-lactams for gram positive infections - AMG → inhibtis protein synthesis - Beta-lactam → Cell-wall inhibitor *Beta-lactam will destroy the cell wall of the organism so gentamicin can get inside and interrupt protein synthesis* **Gentamicin is used for the first 2 weeks, then stopped** - trough monitoring - AEs: nephrotoxicity and ototoxicity

Question 27

What are the 2 Enterococcus that can Cause Endocarditis?

Answer 27

**E. faecalis and E. facecium** - both are from the huma GI tract - E. faecalis tends to be more responsive to antibiotics - Ampicillin + ceftriaxone has evidence for use in E. faecalis IE and cannot be used for E. faecium

Question 28

Monitoring Parameters in Endocarditis

Answer 28

**Symptoms** → daily until resolution **Blood Culture** → q24-48hrs until cutlure negative **Blood Glucose** → daily until normalized **WBC** → daily until normalized **Creatinine** → 2x weekly for duration of therapy **ECHO** → repeat or followup if needed **Side Effects** → dailyfor duration of therapy **TDM (gentamicin, vancomycin)** → per protocol and more frequently (q2-3d) if renal function decreases

Question 29

Endocarditis Prophylaxis

Answer 29

Oral cavity is a large source of infection for those who have risk factors for IE, this includes manipualtion of the gum or periapical region of the teeth, tonsillectomy, and bronchoscopy with biopsy are all high risk procedures - Differing guidelines as to when prophylaxis should be used in dental procedures (SHA says not for routine dental procedures) - Amoxicillin 2g PO once 30-60min prior to procedure (beta-lactam allergy = cefuroxime, doxycycline, azithromycin)

Question 30

Which Patients Have Risk Factors That Indicate Consideration of Prophylaxis?

Answer 30

- Prosthetic heart valve or prosthetic material used for repair - Prior history of IE - Congenital heart disease - Cardiac transplant patient with valvulopathy of the graph