Infectious Heart Disease

Question 1

List the common etiological agents infective endocarditis:

Answer 1

Most are part of the normal microbiota

• Gram (+) bacteria:
  
  • Staphylococcus aureus – anterior nares
  • Coagulase-negative staphylococci (e.g. S. epidermidis) – skin
  • viridans streptococci (e.g. S. sanguis, S. mutans, S. mitis) – oral cavity
  • enterococci (E. faecalis, E. faecium) – GI tract

Question 2

How do the etiological agents gain access to the endocardium?

Answer 2

Access to endocardium provided by transient bacteremia

Question 3

How are IE pathogens successful?

Answer 3

• able to survive antimicrobial components of serum
• able to adhere avidly to endocardium
  
  • viridans streptococci
    
    • dextran (exopolysaccharide)
    • adhesins (surface proteins; FimA, GspB, PblA, PblB) that mediate attachment to platelets and fibrin
  • S. aureus
    
    • fibrinogen-binding adhesins (ClfA, coagulase)

Question 4

How is vegetation beneficial to IE pathogens?

Answer 4

Life in a vegetation:

• heterogeneous matrix of deposited bacteria, platelets, fibrin, other matrix ligands
• protection from immune cells
• bacteria can achieve high densities
• limitations on nutrient exchange, high cell density – bacteria are not growing rapidly

Question 5

How do vegetations impact antibiotic therapy?

Answer 5

Implications for antibiotic therapy:

• Bactericidal activity
• parental administration for sustained activity
• long-term treatment required

Question 6

What does the cell wall determine for bacteria?

Answer 6

Cell Wall (Peptidoglycan) defines shape

1. spheres (cocci)
   
   • single cells
   • pairs (diplococci)
   • chains (streptococci)
   • tetrads (micrococci)
   • grapelike clusters (stapylcocci)
2. rods (bacilli)
   
   • coccobacilli ⇒ long rods
3. spirals
   
   • comma-shaped (Vibrio) ⇒ 4-20 coils (Spirochetes)

Question 7

Cell wall:

Gram (+) vs. Gram (-) bacteria

Answer 7

• Gram Positive: Thick Peptidoglycan
• Gram Negative: Thin Peptidoglycan
  
  • Crosslinked to the Outer Membrane
    
    • Outer Membrane:Permeability barrier

Question 8

What is the laboratory delineation of IE pathogens?

Answer 8

1. **Blood culture **
2. Gram-stain
   
   • Positive vs. Negative
3. Shape
   
   • Cocci vs. Rods vs. Other
4. Organization
   
   • Chains vs. Clusters
5. Genus
   
   • Streptococcus vs. Staphylococcus
6. Other tests

Question 9

List the cell wall antibacterial agents:

Answer 9

• cefazolin, ceftriaxone, penicillin, nafcillin
• vancomcyin
• daptomycin

Question 10

List the protein synthesis inhibitors:

Answer 10

gentamicin

Question 11

List the RNA synthesis inhibitor:

Answer 11

rifampin

Question 12

Describe the mechanism for β-lactam antibiotics:

Answer 12

block peptidoglycan crosslinking by inhibting PBPs

Question 13

How do β-lactam antibiotics differ?

Answer 13

Four basic types of β-lactam

• modification at “R” groups alters properties of the antibiotic

Question 14

How do bacteria resist β-lactam antibiotics?

Answer 14

• Mutations in PBPs that prevent binding of β-lactam antibiotics (modification of antibiotic target)
  
  • Most common mechanism of β-lactam resistance found in Gram-positive bacteria:
    
    • Streptococcus
    • methicillin-resistant Staphylococcus aureus (MRSA)

Question 15

How does Vancomycin differ from the β-lactam antibiotics?

Answer 15

• Glycopepetide antibiotic
• Mechanism: binds to D-Ala-D-Ala
  
  • Blocks PBPs from transglycosylation/transpeptidation
• Not effective against G (-) due to outer membrane (permeability barrier)
• Used for β-lactam resistant infections (e.g. MRSA) or in patients w/ β -lactam hypersensitivity

Question 16

What is the mechanism of resistance for Vancomycin? Where are the genes for this found?

Answer 16

• Mechanism of resistance: Modification of antibiotic target
• Bacteria acquire genes encoding machinery to produce altered peptidoglycan structure that lacks D-Ala-D-Ala groups
  
  • contain D-Ala-D-Lac
• Vancomycin is unable to bind efficiently to these modified precursors
• Genes encoding vancomycin resistance are usually found on plasmids or transposons

Question 17

Describe the mechanism for Daptomycin.

What is its spectrum?

Answer 17

• **Lipopeptide **
• Bactericidal, narrow spectrum (Gram+ bacteria)
• Mechanism of action:
  
  • thought to bind to and disrupt the cytoplasmic membrane
  • possibly via loss of membrane potential
  • leading to death

Question 18

Describe the mechanism of Rifampin.

How is it useful?

Answer 18

• Bactericidal, narrow spectrum (G+ bacteria)
• Mechanism of action:
  
  • binds to and inhibits RNA polymerase to prevent gene expression (inhibits transcription of DNA into RNA)
  • Resistant mutants arise due to point mutations in the target of the drug
    
    • RpoB subunit of RNA polymerase
• Not generally used as monotherapy – use in combinations for synergy

Question 19

• What do the aminoglycosides target?
• What are adverse side effects?
• How are they resisted?

Answer 19

• Mechanism of action: bind irreversibly to 30S ribosomal subunit and cause misreading and premature release of ribosome from mRNA
  
  • incorporation of incorrect amino acid into growing protein
• Not good for monotherapy:
  
  • do not penetrate many Gram-positives well
  • usually used in combination with a cell-wall-active agent to enhance penetration
• Adverse effects: Ototoxic and nephrotoxic
• Mechanism of resistance: Enzymatic modification of the antibiotic to prevent aminoglycoside binding to the ribosome

Question 20

Define endocardidtis

Answer 20

inflammatory disease of the endocardium

Question 21

What is Libman-Sacks endocarditis?

Answer 21

sterile endocarditis

• related to systemic lupus erythematosus

Question 22

Difference between acute IE and subacute IE:

Answer 22

• Acute IE:
  
  • invasive, caused by pathogenic organisms that give rise to a toxic course of disease
  • characterized by a more severe and sudden onset than subacute IE
• Subacute IE:
  
  • more indolent course of disease caused by less pathogenic bacteria

Question 23

What are predisposing factors for IE?

Answer 23

• valvular heart disease (rheumatic heart disease, congenital heart disease)
• prosthetic devices (valves, pacemakers)
• intravenous drug use

Question 24

What simultaneous events occur that result in IE?

Answer 24

1. Alteration of valvular surface to produce a site suitable for bacterial adherence and colonization
   
   • trauma
   • turbulence
   • result of congenital heart defect
2. Valvular alterations result in deposition of:
   
   • platelets, fibronectin, fibrin, other matrix ligands
   • Non-bacterial thrombotic endocarditis -NBTE
3. Transient bacteremia enables bacteria to reach the site and adhere, resulting in colonization and persistence
   
   • resulting mass ⇒ “vegetation”

Question 25

**Rank the incidence of IE in heart valves** (most common to least common):

Answer 25

**Mitral \> aortic** **\>** tricuspid **\>** pulmonary * **mitral and aortic are the most common** (left-sided) * **triscupid valve** is most often affected in **IV drug abusers**

Question 26

What processes contribute to the clinical manifestations of IE?

Answer 26

**Contributing factors:** 1. _infectious process on the valve_ and its complications 2. _embolization_ to other organs 3. _persistent bacteremia_, often with metastatic foci of infection 4. _immunopathologic factors_ * As a result, the _clinical presentation of IE is highly variable_ and diagnosis can be delayed

Question 27

What are some complications that can arise from IE?

Answer 27

* **congestive heart failure** (CHF) * _conduction defects_ (heart block) * _major embolic episodes_ (myocardial infarction, stroke) * _systemic abscesses_ * **renal failure** * _mycotic aneurysm_ (infection of artery wall)

Question 28

A definitive clinical diagnosis of IE is made based on the presence of:

Answer 28

**Modified Duke Criteria:** * 2 major criteria **or** * 1 major criterion and 3 minor criteria **or** * 5 minor criteria

Question 29

What are the **major microbiologic criteria** for IE?

Answer 29

* _Two blood cultures positive for organisms typically found in patients with IE in the absence of an alternative primary focus_ * staphylococci, streptococci, enterococci, HACEK * _Blood cultures persistently positive_ from cultures drawn more than _12 hours apart_ * _3+ separate blood cultures_ drawn at least _1 hour apart_ * _Positive serology for Coxiella burnetti _

Question 30

What are the **major echocardiographic criteria** for IE?

Answer 30

* _Echocardiogram positive for IE_ * documented by an oscillating intracardiac mass on a valve or on supporting structures in the path of regurgitant jets * on implanted material in the absence of an alternative anatomical explanation * _Myocardial abscess_ * _Development of partial dehiscence of a prosthetic valve_ * _New-onset valvular regurgitation_

Question 31

What are the minor criteria for IE?

Answer 31

* _Predisposing heart condition or intravenous drug use_ * _Fever_ of 38°C (100.4°F) or higher * _Vascular phenomena_, including major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, or Janeway lesions * _Immunological phenomenon_ such as glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor * _Positive blood culture results not meeting major criteria or serologic evidence of active infection with an organism consistent with IE_ * Brucella, Legionella

Question 32

What **types of echocardiography** can be used to aid in IE diagnosis?

Answer 32

1. **Transthoracic echo (TTE)** * _~60% sensitive_ for detecting vegetations, primarily for **right-sided IE** 2. **Transesophageal echo (TEE)** * _~95% sensitive_ for detecting vegetations and _perivalvular abscesses_ * **preferred test for evaluation of prosthetic valves** * Indicated in patients with suspected IE

Question 33

What are the **most common G- bacteria** that can cause IE?

Answer 33

***HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)*** * normal flora of the _oropharynx_ * generally fastidious _Gram-negative rods_ that require _special culture media_ and _prolonged periods of culture_ for isolation

Question 34

What **bacteria** are associated with **acute IE**?

Answer 34

* **Staphylococcus aureus** * **Coagulase-negative staphylococci**

Question 35

What **bacteria** are associated with **subacute IE**?

Answer 35

* **Viridians streptococci** * **Enterococci** * **HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)**

Question 36

What are the **most common fungi** associated with IE?

Answer 36

***Candida***

Question 37

When would surgery be necessary as treatment for IE?

Answer 37

* **Surgical therapy to debride or replace affected valves:** * _severe valvular failure_ occurs * _perivalvular abscess_ needs drainage