Pharm - Glycopeptides & MISC Flashcards by amanda kastel

name 3 glycopeptide antibiotics

vancomycin
telavancin
dalbavancin

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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 +

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explain the MOA of vancomycin

binds D-ala D-ala to prevent transglycosylation and transpeptidation

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true or false

unlike B lactams, vancomycin does NOT structurally mimic D-ala D-ala

true

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through which bonds does vancomycin bond D-ala D-ala

FIVE HYDROGEN BONDS

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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

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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

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intermediate vancomycin resistance is due to……

too many D-Ala-D-Ala on thickened cell wall – serves as dead end targets for vanco

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vanco is a _______ dependent _____ agent

time dependent bactericidal

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explain the antimicrobial spectrum of vancomycin

GRAM POSITIVE BACTERIA, staph producing b lactamases, and for many gram positive anaerobes like C DIFF

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vancomycin is synergistic in vivo with…..

gentamicin and streptomycin (aminoglycosides)

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name some clinical uses for vanco

pneumonia treatment for MRSA

C diff

osteomyelitis, endocarditis, SSTI, bone/joint infections

CNS inf like community aquired meningitis

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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

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vanco is administered by ______ for serious infections

IV infusion

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true or false

vanco is widely distributed

TRUE

gets to CSF - can treat meningitis

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how is vanco mainly excreted

through KIDNEYS - watch renal function

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vanco has clinically relevant __________

PAE (post antibiotic effect)
can be 2-6.5 hrs

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important consideration when giving vanco

serum concentrations should be monitored

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name some AE of vanco

ototoxicity (ear) and nephrotoxicity (kidney)

also infusion reactions like flushing (redness) bc of histamine

GIVE SLOWLY, AND GIVE ANTIHISTAMINES

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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

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disadvantage of telavancin vs vancomycin

telavancin is teratogenic and not used in pregnant women

(not a concern for vanco)

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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!!!

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ADVANTAGE of dalbivancin and oritavancin over vanco

does NOT require dose adjustment based on renal or hepatic impairment

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spectrum of telavancin

gram positive bacteria

active against many strains with reduced susceptibility to vanco

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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