Pharm - Glycopeptides & MISC Flashcards
name 3 glycopeptide antibiotics
vancomycin
telavancin
dalbavancin
just from looking at the structure of glycopeptides, what can you say about their activity
they are very bulky - cannot cross the membrane and not given orally - given by IV.
also, so many peptide bonds - will be very susceptible to rapid hydrolysis if given orally.
also, active for GRAM POSITIVE bacteria bc for gram negative they must cross a membrane to get to the cell wall, but not for +
explain the MOA of vancomycin
binds D-ala D-ala to prevent transglycosylation and transpeptidation
true or false
unlike B lactams, vancomycin does NOT structurally mimic D-ala D-ala
true
through which bonds does vancomycin bond D-ala D-ala
FIVE HYDROGEN BONDS
name and explain 2 methods of vancomycin resistance
Van-A: vancomycin resistant staph aureus. happens when D-Ala-D-Ala is converted to D-Ala-D-LACTATE. This decreases the number of hydrogen bonds formed from 5->4 which reducess binding by more than 100 fold
Van B: The cell wall is thickened with INCREASED NUMBERS of D-Ala-D-Ala residues - serve as dead end binding sites for vanco. Vancomycin-intermediate resistance strains of staph aureus
differentiate and explain the significance of the MIC of Van-A resistance vs Van-B resistance
Van-A: MIC is greater than 16mcg/mL
Van-B: MIC is between 4-8mcg/mL
therefore, Van-A resistance is much more significant
intermediate vancomycin resistance is due to……
too many D-Ala-D-Ala on thickened cell wall – serves as dead end targets for vanco
vanco is a _______ dependent _____ agent
time dependent bactericidal
explain the antimicrobial spectrum of vancomycin
GRAM POSITIVE BACTERIA, staph producing b lactamases, and for many gram positive anaerobes like C DIFF
vancomycin is synergistic in vivo with…..
gentamicin and streptomycin (aminoglycosides)
name some clinical uses for vanco
pneumonia treatment for MRSA
C diff
osteomyelitis, endocarditis, SSTI, bone/joint infections
CNS inf like community aquired meningitis
when is the only time vanco is given orally?
explain why
for C difficile
bc the bacteria is in the intestines. while most of the drug will be destroyed, whatever is left can kill the c diff in the intestines
vanco is administered by ______ for serious infections
IV infusion
true or false
vanco is widely distributed
TRUE
gets to CSF - can treat meningitis
how is vanco mainly excreted
through KIDNEYS - watch renal function
vanco has clinically relevant __________
PAE (post antibiotic effect)
can be 2-6.5 hrs
important consideration when giving vanco
serum concentrations should be monitored
name some AE of vanco
ototoxicity (ear) and nephrotoxicity (kidney)
also infusion reactions like flushing (redness) bc of histamine
GIVE SLOWLY, AND GIVE ANTIHISTAMINES
differentiate between the structures of vancomycin and telavancin and what this means about telavancin’s activity
telavancin is a LIPOglycopeptide - not just a glycopeptide
therefore, it has the same MOA as vanco (D-Ala-D-ala binding) + an additional mechanism of disrupting the bacterial cell membrane potential by increasing its permeability
its lipophilic portion allows it to interact with the membrane
disadvantage of telavancin vs vancomycin
telavancin is teratogenic and not used in pregnant women
(not a concern for vanco)
dalbavancin and oritavancin MOA
also a lipoglycopeptide
has THREE MOAs
- bind D-Ala-D-Ala
- Bind membrane to affect potential and permeability
- INHIBIT RNA SYNTHESIS!!!
ADVANTAGE of dalbivancin and oritavancin over vanco
does NOT require dose adjustment based on renal or hepatic impairment
spectrum of telavancin
gram positive bacteria
active against many strains with reduced susceptibility to vanco
telavancin is a ____ derivative of vancomycin
semisynthetic
dalbavancin and oritavancin are NOT used for ________ infections
VRE
(vanco resistant enterococci)
briefly explain structure of daptomycin
cyclic lipopeptide
does NOT contain sugar
why is daptomycin clinically important
can be used for vanco resistant strains
daptomycin has _________- dependent ________- activity
concentration dependent bactericidal
explain the MOA of daptomycin
it’s a surfactant - has hydrophilic head and hydrophobic tail
CALCIUM DEPENDENT - binds to membrane of bacteria and forms a PORE - which causes removal of electrolytes and ultimate death of the bacteria
explain how daptomycin resistance can happen
by mutations in the mprF gene that regulates the cell membrane charge
what kind of bacteria is dapto used for
ALL GRAM POSITIVE
cant get thru membrane of negative
explain the spectrum of vanco vs dapto
similar, but dapto is active against vanco-resistant dtrains of staph aureus and enterococci
name something daptomycin CANNOT be used for and why
CAP (community acquired pneumonia)
bc the alveoli make their own surfactant which neutralizes dapto (a surfactant)
how is daptomycin administered
IV route
name some AE of daptomycin
damage to MUSCULOSKELETAL SYSTEM – rhabdomyolysis, esp when combined with statins or aminoglycosides
also risk of nephro and hepatic toxicity
just by the name “fosfomycin” what can you say about the structure
contains a phosphate group
what structure does fosfomycin mimic
phosphoenol pyruvate (PEP)
explain the mechanism of fosfomycin
acts on sugar polymerization of the bacterial cell wall
NORMALLY:
PEP + NAG, through enolpyruvate transferase, will form UDP-NAM which forms NAM
NAM is essential sugar for the bacterial cell wall. not enough sugars = not good cell wall
fosfomycin inhibits enolpyruvate transferase (by mimicing PEP), the enzyme that produces NAM
what is the spectrum of fosfomycin and how is it able to do this
both gram (+) and (-)!!!!
because unlike vanco and its derivatives - it’s a very small molecule - able to get through the membrane of gram (-) into where the sugars are being synthesized for the cell wall
how can resistance to fosfomycin happen
normally, the drug is transported in by glycerophosphate or glucose-6-phosphate transport system.
if mutation in these transporters, not enough of the drug will get into the cell
fosfomycin has narrow or broad spectrum
broas - both gram pos and neg
is fosfomycin cidal or static
cidal
2 main uses fosfomycin
-uncomplicated UTI in women
-abdominal infections
main AE of fosfomycin and why
c diff diarrhea
bc it’s broad spectrum - kills lot of good bacteria and c diff can take over
fosfomycin has synergy with what 3 other antibiotics
beta lactams
aminoglycosides
fluoroquinolones
explain the MOA of bacitracin
interferes with the lipid carrier system of bacteria
normally, the lipid carrier carries peptidoglycan subunits from within the bacteria and goes up to the membrane to deliver the units
in order for the carrier to go ack down and get more “building blocks”, it must be dephosphorylated. however, bacitracin prevents this dephosphorylation by binding.
therefore, the carrier can’t get back in to get more subunits for the cell wall and the bacteria can’t survive
why is bacitracin not used systemically
not well absorbed and also highly nephrotoxic
only time bacitracin is used orally
for c diff diarrhea
what is bacitracin used for
used topically for surface lesions of the skin - on wounds or on mucous membranes
preparations of bacitracin
can have neomycin and polymyxin as topical OTC product
polymyxin MOA
interacts with phospholipids - disrupts the structure of bacterial cell membrane.
binds lipid A portion of LPS (endotoxin) on the outer layer of gram (-) bacteria and inactivates it
resistance to polymyxin
some bacteria way prevent access to their cell wall
spectrum of polymyxin
gram (-) bacteria (binds LPS!)
lot of nosocomial infection coverage like pseudomonas
name 3 things in polymyxin group of antibiotics
polymyxin B (parenteral)
colistin (topical and oral)
colistimethate (oral)
chemically, what do the polymyxins look like and what does this say about their activity
cationic detergents - like surfactants - have head and tail = therefore, must interact with membrane
true or false
polymyxin is NOT well absorbed orally
TRUE
given parenterally
only given oral for c diff diarrhea
AE polymyxin
nephrotixicity (renally excreted also - need adjustment)
neuromuscular blockade - muscular weakness
systemic uses of the polymyxins
for multi-drug resistant gram negative organisms
used systemically as like a last resort
name of the polymyxin used topically otic and ophthalmic
polymyxin B sulfate
chemically, what is fidaxomicin
a macrolide
true or false
fidaxomide is NOT a cell wall synthesis inhibitor
TRUE
uses of fidaxomicin
bactericidal against c diff
MOA fidaxomicin
bactericidal
inhibits RNA synthesis by RNA polymerases
true or false
fidaxomicin is bacteriostatic
false - bactericidal
fidaxomicin has broad or narrow spectrum
narrow
how does resistance to fidaxomicin happen
mutations in bacterial RNA polymerase
only treatment fidaxomicin
clostridium difficile associated diarrhea
MOA bezlotoxumab and clinical use
how can you remember
bezloTOXumab
binds to the toxin B or c. diff — NOT C DIFF ITSELF
by binding toxin, reduces the recurrence of C diff infection. NOT USED TO TREAT C DIFF AND NOT AN ANTIBIOTIC
only used in conjunction with AB to treat c diff infection
how is bezlotoxumab administered
IV infusion over 60 mins (SLOWLY)
AE of bezlotoxumab
incidence of heart failure in CHF patients and potential for immunogenecity
bacterial target of vanco*****
a dipeptide
D-ala-D-ala
