What are implications for antibiotic therapy when trying to treat a person with vegetations?
(*Infectious Endocarditis*)1) Bactericidal activity (no immune access)
2) Parental administration for sustained activity
3) Prolonged therapy requiredWhat are different shapes of bacteria?Peptidoglycan defines shape of bacteriaWhat is the difference between Gram positive and Gram negative bacteria?What are the most common cell wall agents to treat *Infectious Endocarditis*1) Cefazolin
2) Ceftriaxone
3) Penicillin
4) Nafcillin
5) Vancomycin
6) DaptomycinWhat are the most common protein synthesis inhibitors to treat *Infectious Endocarditis*GentamicinWhat are the most common RNA synthesis inhibitors to treat *Infectious Endocarditis*RifampicinWhat are mechanisms of Resistance to Beta-lactam antibiotics?1) Altered PBPs that prevent binding of Beta-lactam antibiotics (mecA binding cassette)
2) Production of inactivating enzymes (beta-lactamases
3) Modification of porins (permeability barrier)T/F: If MRSA is resistant to oxacillin, then effectively resistant to all beta-lactamsTrueEnterococci are naturally tolerant to beta-lactams and require combination therapy. What does the combination therapy consist of?Cell well agent such as
1) Cefazolin OR
2) Ceftriaxone OR
3) Penicillin OR
4) Nafcillin OR
5) Vancomycin OR
6) Daptomycin
AND
GentamicinWhat is the MOA of *Vancomycin*?Vancomycin binds to D-Ala-D-Ala at the end of peptide side chain in peptidoglycan precursors, blocking PBPs from catalyzing transglycosylation/ transpeptidation steps of peptidoglycan synthesisT/F: *Vancomycin* is effective on many grams positive organisms, but not effective on Gram-negative organisms due to permeability barrier of gram negative outer membraneTrueWhat is the mechanism of resistance to *Vancomycin*?Modification of antibiotic target
1) Bacteria acquire encoding machinery to produce altered peptidoglycan structure that lacks D-Ala-D-Ala groups
2) Vancomycin is unable to bind efficiently to these modified precursors
3) Genes encoding vancomycin resistance are usually found on plasmids or transposons that can be easily transferred to other bacteriaWhat is the MOA of *Daptomycin*?Thought to bind to and disrupt the cytoplasmic membrane, possibly via loss of membrane potential, leading to deathWhat is the therapeutic indication for *Daptomycin*?Used for infections caused by antibiotic-resistant bacteria because it employs a novel mechanism of action that retains activity against resistant bacteriaWhat is the MOA of *Rifampin*?Binds beta subunit of bacteria RNA polymerase to inhibit polymerase activity, thereby preventing RNA synthesis
*RAPID SELECTION FOR RESISTANT MUTANTS*What is the Mechanism of resistance of *Rifampin*?Acquisition of mutations in Beta sub-unit of RNA polymerase that prevent antibiotic from binding
*Not generally used as monotherapy- use in combinations for synergy*What is the MOA of *Gentamicin*?Bind irreversibly to 30S ribosomal subunit; stops initiation of protein synthesis, cause misreading (incorporation of incorrect AA into growing protein) and premature release of ribosome from mRNA.Is *Gentamicin* effective for monotherapy?No
Does not penetrate many Gram-positives wellWhat are the adverse effects of *Gentamicin*?Ototoxic and nephrotoxicWhat is the mechanism of resistance for *Gentamicin*?Enzymatic modification of the antibiotic (transferases catalyze addition of adenyl, acetyl, or phosphoryl group) to prevent aminoglycoside binding to the ribosome
*Genes encoding transferases are often located on mobile genetic elements (plasmids, transposons) that facilitate transfer to other bacteria*T/F: The most common etiological agents of infectious endocarditis are Gram-positive members of normal microbiotia that gain access via transient bacteremiasTrue
