Intro to infectious Agents HD Flashcards
Most common agents that cause infectious endocarditis are:
members of normal microbiota
• 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
Access to endocardium provided by
transient bacteremia
Properties of successful IE pathogens:
- able to survive antimicrobial components of serum
* able to adhere avidly to endocardium
How does viridans streptococci mediate adeherance in the endocardium?
• dextran (exopolysaccharide)
• adhesins (surface proteins; FimA, GspB, PblA, PblB) that
mediate attachment to platelets and fibrin
How does S.aureus mediate adherance in endocardium
• fibrinogen-binding adhesins (ClfA, coagulase)
What does it mean when we say infectious endocarditis bacteria ‘live in a vegitation’
heterogeneous matrix of deposited bacteria, platelets, fibrin, other matrix ligands
bacteria can achieve high densities
Why are infectious endocarditis bacterial concerning and difficult to erradicate?
protection from immune cells
*limitations on nutrient exchange, high cell density – bacteria are not growing rapidly; most antibiotics attack rapidly growing bacteria
Implications for antibiotic therapy in IE?
- Bactericidal activity
- parental administration for sustained activity
- long-term treatment required
Thick peptidoglycan, stains purple d/t iodine and not saffron red
Gram + bacteria
Thin peptidoglycan wall, crosslinked to outer membrane; outer membrane has permeability layer and stains saffron red
Gram - bacteria
Stain/shape/ organization for streptococcus
Gram +
in Cocci
in chain
= streptococcus
stain/shape/organization for staphlococcus
Gram +
Cocci
Clusters
Antibiotics that block peptidoglycan crosslinking
B-lactams;
inhibit the L-ala–D-ala linkage
B lactams are bacteriostatic or bacteriocidal
bacteriostatic
Four basic types of β-lactam – modification at______alters properties of the
antibiotic
“R” groups
nafcillin, peniclillin and cefazolin and ceftriaxone
How do bacteria develope resistance to B-lactams?
Mutations in PBPs that prevent binding of β-lactam antibiotics
(modification of antibiotic target)
Most common mechanism of B- lactam resistance found in
Gram-positive bacteria, such as Streptococcus and methicillin-resistant Staphylococcus
aureus (MRSA)
Vancomycin is a ________
What’s its mechanism?
glycopeptide
binds to D-ala-D-ala at end of peptide chain in peptidoglycan precursors… blocks PBPs from catalyzing transfer
Vancomycin is effective in what type of bacteria?
Gram + and in patients with bacterias resistant to (not Gram - d/t permeability barrier of Gram - outer membrane)
Mechanism of resistance against vancomyocin
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 in place of D-Ala-D-Ala); vancomycin is unable to bind
efficiently to these modified precursors
How do bacteria acquire resistance to vanocmyocin?
Genes encoding vancomycin resistance are usually found on plasmids or transposons that
can be easily transferred to other bacteria
VRE is most common in:
hospital settings
thought to bind to and disrupt the cytoplasmic
membrane, possibly via loss of membrane potential, leading to death
Daptomyocin
Daptomycin is:
bacteriacidal/static
broad or narrow spectrum
bacteriacidal
narrow (G+)
used for infections caused by antibiotic-resistant bacteria because it employs a novel mechanism of action that retains activity against
resistant bacteria
Daptomycin
Mech of action of Rifampin
binds to and inhibits RNA polymerase to prevent gene expression (stops transcription of DNA into RNA)
How does bacterial develop resistance to Rifampin?
due to point mutations in the target of the drug
RpoB subunit of RNA polymerase
How do you administer Rifampin?
in synergy with other antibiotics
bind irreversibly to 30S ribosomal subunit and cause
misreading (incorporation of incorrect amino acid into growing protein) and
premature release of ribosome from mRNA
Aminoglycosides
Gentamicin is a
aminoglycoside
Why do we not use aminoglycosides on G+
because they don’t penetrate well so give them with another antibiotic, such as a cell-wall active agent
adverse effects of aminoglycosides (gentamicin)
ototoxic and nephrotoxic
Mech of resistance of bacteria to aminoglycosides
Enzymatic modification of the antibiotic (transferases
catalyze addition of adenyl, acetyl, or phosphoryl group) to prevent aminoglycoside binding to the ribosome
important virulence determinants in infectious endocarditis
factors that promote adherence to heart valves (dextran, cell surface proteins)
