Infectious Heart Disease Flashcards
List the common etiological agents infective endocarditis:
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
How do the etiological agents gain access to the endocardium?
Access to endocardium provided by transient bacteremia
How are IE pathogens successful?
- 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)
-
viridans streptococci
How is vegetation beneficial to IE pathogens?
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
How do vegetations impact antibiotic therapy?
Implications for antibiotic therapy:
- Bactericidal activity
- parental administration for sustained activity
- long-term treatment required
What does the cell wall determine for bacteria?
Cell Wall (Peptidoglycan) defines shape
-
spheres (cocci)
- single cells
- pairs (diplococci)
- chains (streptococci)
- tetrads (micrococci)
- grapelike clusters (stapylcocci)
-
rods (bacilli)
- coccobacilli ⇒ long rods
-
spirals
- comma-shaped (Vibrio) ⇒ 4-20 coils (Spirochetes)
Cell wall:
Gram (+) vs. Gram (-) bacteria
- Gram Positive: Thick Peptidoglycan
-
Gram Negative: Thin Peptidoglycan
- Crosslinked to the Outer Membrane
- Outer Membrane:Permeability barrier
- Crosslinked to the Outer Membrane
What is the laboratory delineation of IE pathogens?
- **Blood culture **
-
Gram-stain
- Positive vs. Negative
-
Shape
- Cocci vs. Rods vs. Other
-
Organization
- Chains vs. Clusters
-
Genus
- Streptococcus vs. Staphylococcus
- Other tests
List the cell wall antibacterial agents:
- cefazolin, ceftriaxone, penicillin, nafcillin
- vancomcyin
- daptomycin
List the protein synthesis inhibitors:
gentamicin
List the RNA synthesis inhibitor:
rifampin
Describe the mechanism for β-lactam antibiotics:
block peptidoglycan crosslinking by inhibting PBPs
How do β-lactam antibiotics differ?
Four basic types of β-lactam
- modification at “R” groups alters properties of the antibiotic
How do bacteria resist β-lactam antibiotics?
-
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)
- Most common mechanism of β-lactam resistance found in Gram-positive bacteria:
How does Vancomycin differ from the β-lactam antibiotics?
- 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
What is the mechanism of resistance for Vancomycin? Where are the genes for this found?
- 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
Describe the mechanism for Daptomycin.
What is its spectrum?
- **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
Describe the mechanism of Rifampin.
How is it useful?
- 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
- What do the aminoglycosides target?
- What are adverse side effects?
- How are they resisted?
-
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
Define endocardidtis
inflammatory disease of the endocardium
What is Libman-Sacks endocarditis?
sterile endocarditis
- related to systemic lupus erythematosus
Difference between acute IE and subacute IE:
-
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
What are predisposing factors for IE?
- valvular heart disease (rheumatic heart disease, congenital heart disease)
- prosthetic devices (valves, pacemakers)
- intravenous drug use
What simultaneous events occur that result in IE?
-
Alteration of valvular surface to produce a site suitable for bacterial adherence and colonization
- trauma
- turbulence
- result of congenital heart defect
-
Valvular alterations result in deposition of:
- platelets, fibronectin, fibrin, other matrix ligands
- Non-bacterial thrombotic endocarditis -NBTE
-
Transient bacteremia enables bacteria to reach the site and adhere, resulting in colonization and persistence
- resulting mass ⇒ “vegetation”
Rank the incidence of IE in heart valves (most common to least common):
Mitral > aortic > tricuspid > pulmonary
- mitral and aortic are the most common (left-sided)
- triscupid valve is most often affected in IV drug abusers
What processes contribute to the clinical manifestations of IE?
Contributing factors:
- infectious process on the valve and its complications
- embolization to other organs
- persistent bacteremia, often with metastatic foci of infection
- immunopathologic factors
- As a result, the clinical presentation of IE is highly variable and diagnosis can be delayed
What are some complications that can arise from IE?
- congestive heart failure (CHF)
- conduction defects (heart block)
- major embolic episodes (myocardial infarction, stroke)
- systemic abscesses
- renal failure
- mycotic aneurysm (infection of artery wall)
A definitive clinical diagnosis of IE is made based on the presence of:
Modified Duke Criteria:
- 2 major criteria
or
- 1 major criterion and 3 minor criteria
or
- 5 minor criteria
What are the major microbiologic criteria for IE?
-
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 _
What are the major echocardiographic criteria for IE?
-
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
What are the minor criteria for IE?
- 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
What types of echocardiography can be used to aid in IE diagnosis?
-
Transthoracic echo (TTE)
- ~60% sensitive for detecting vegetations, primarily for right-sided IE
-
Transesophageal echo (TEE)
- ~95% sensitive for detecting vegetations and perivalvular abscesses
- preferred test for evaluation of prosthetic valves
- Indicated in patients with suspected IE
What are the most common G- bacteria that can cause IE?
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
What bacteria are associated with acute IE?
- Staphylococcus aureus
- Coagulase-negative staphylococci
What bacteria are associated with subacute IE?
- Viridians streptococci
- Enterococci
- HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)
What are the most common fungi associated with IE?
Candida
When would surgery be necessary as treatment for IE?
-
Surgical therapy to debride or replace affected valves:
- severe valvular failure occurs
- perivalvular abscess needs drainage
