Polymyxins Flashcards
Polymyxins include 5 different chemical compounds but only 2 are used clinically:
B and E (colistin)
Polymyxin structure
cationic polypeptide
Polymyxin is an _____
amphiphilic molecule
Polymyxin has a hydrophilic ____ and a hydrophobic ____
peptide ring; tail
Polymyxin MOA
positively charge amino groups (L-Dab) align with lipopolysaccharide of Gram - and then hydrophobic tail interacts with bacterial cell membrane this causes increase in permeability of the cell wall and inner membrane allowing leakage of contents
PolymyxinB oral absorption
nominal
PolymyxinB 1/2 life
6 hours (long)
PolymyxinB elimination
not renal
Colistin oral absorption
nominal
Colistin 1/2 life
1-3 hours; shorter
Colistin elimination
renal
Polymyxins are ____ dependent
concentration
Polymyxins are bactericidal/bacteriostatic
bactericidal
Colistin tissue penetration
poor into lung, pericardial fluid, and CSF
inhaled colistin is used to optimize
lung exposure
Conversion of CMS to colistin in kidneys causes
high urine concentrations
Colistin is administered as
inactive prodrug (CMS)
CMS is cleared by
renal excretion or converted to colistin (active agent)
In patients with good renal function, CMS clearance is ____ than coversion leading to ____
faster; low serum concentrations
Variables affecting colistin concentrations
batch to batch variability in composition of CMS
variability based on renal function
Polymyxin B is administered
active form
Polymyxin B has improved _____ over colistin
serum concentrations
Polymyxin B is reabsorbed in the kidneys resulting in
low urinary concentrations of the agent
CMS goes through mostly renal clearance and a small amount of other clearance this results in
high concentration of CMS and colistin in urine
Left over CMS (that didn’t get renally cleared) conversion to colistin results in
largely Colistin clearance by other means and small % of colistin renally cleared
Polymyxin B primary goes through
other clearance and small amount of renal clearance which results in low concentrations of it in the urine
Polymyxins spectrum coverage
GRAM - ONLY
dark red: h. influenzae, E. coli, klebsiella, enterobacter, citrobacter, p. aeruginosa, acinetobacter
light red: m. cattarhalis
Misc: mycobacterium, not active against steno
Polymyxins mechanisms of resistance
alterations of LPS
increase production of capsule polysaccharide
efflux pumps
increased levels of H1
Polymyxins adverse effects
nephrotoxicity onset within 1 week and dose dependent (coadministration with other nephrotoxins may increase risk)
neuromuscular blockade
- dose dependent and reversible
- blocks release of acterylcholine
- weakness, paresthesia, ataxia
Polymyxin B is considered _____ than colistin since
more reliable; administered in its active form
Polymyxin B does/does not need renal adjustment
does not
Colistin is preferred in treating
lower UTI
Polymyxin B is preferred in treating
systemic use in invasive infections
Polymyxin B are better used as
combination therapy
