protein synthesis inhibitors Flashcards
MOA clindamycin
inhibit protein synthesis by binding only to 50S
clindamycin: bacteriostatic or bactericidal?
bacteriostatic
MOR clindamycin
presence of erm gene, which alters the 50S binding site
no activity of mef gene against clindamycin
main area of use for clindamycin
anaerobic infections peptostreptococcus actinomyces bacteriodes (use metronidazole instead) prevotella fusobacterium clostridium spp. (excluding C. difficile)
best way to test for CA MRSA resistance to clindamycin?
SSSI infections due to MRSA, give clindamycin to see if theyre susceptible or not
clindomycin have to be givenIV or PO?
no, completely and rapidly absorbed (90%)
CSF distribution clindomycin?
poor distribution
clindomycin eliminated by hemodialysis?
no
elimination mechanism for clindomycin?
primarily by liver
primary clinical use clindomycin
anaerobic infections outside of the CNS, SSSI infections due to CA MRSA
the one major adverse effect clindomycin
one of the worst inducers of C. difficile colitis
3 macrolides in clinical use
erythromycin, clarithromycin, azithromycin
improvements due to purifying erythromycin into azithromycin and clarithromycin
better bioavailability
better tissue penetration
prolonged half lives
improved tolerability
MOA macrolides
inhibit protein synthesis by binding the 50S subunit to suppress protein synthesis
macrolides: bacteriostatic or bactericidal
bacteriostatic
MOR macrolides in the US
mef gene encoding active efflux which confers a low level of resistance to macrolides
MOR macrolides in Europe
erm gene encoding altered target sites on 50S which confers a high level of resistance to macrolides
spectrum of activity for macrolides in G- aerobes (including macrolides rankings)
H. influenzae (not erythromycin)
M. catarrhalis
Neisseria
azithromycin > clarithromycin > erythromycin
G- bacteria group that macrolides have NO activity against
enterobacteriacieae
spectrum of activity for macrolides in G+ aerobes (including macrolides rankings)
MSSA PSSP Group and viridans streptococci bacillus corynebacteria
activity macrolides against atypical bacteria
macrolides are the main mechanism of treatment for atypical bacteria
legionella pneumonia (water fountain infections)
chlamydia
mycoplasma
Treatment of mycobacterium avid complex with these macrolides…
only azithromycin and clarithromycin
absorption of erythromycin PO
variable absorption that is enhanced by giving with enteric coating or in ester salt formulations (destroyed by gastric acid)
absorption of clarithromycin PO
well absorbed (55%) and acid tolerable unchanged by the presence of food
macrolides used in respiratory tract infections
azithromycin is best if H. influenza is suspected
mainstay treatment that macrocodes are used for
CA pneumonia together with ceftriaxone
macrolide used to treat STIs
single, 1 g dose of azithromycin
macrolide used for treatment of MAC
clarithromycin or azithromycin
macrolide use for prophylaxis for MAC
azithromycin
most important adverse effect of using macrolides
prolonged QT interval, contraindicated in patients already on anti arrhythmic medications
drug drug interactions of macrolides
erythromycin and clarithromycin interact with CYP450 enzymes and alter the metabolism of drugs utilizing this system
MOA streptogramins
both quinpristin and daltopristine bind the 50S subunit to inhibit bacterial protein synthesis
MOR streptogramins
alteration of the ribosomal binding site (erm) and enzymatic inactivation
spectrum of activity streptogramins
MRSA
PRSP
VRE
streptogramins: bactericidal or bacteriostatic?
bacteriostatic
streptogramins: time or concentration dependent?
time
absorption of streptogramins PO
only available IV
distribution streptogramins to the CSF
does not penetrate the CSF
clinical uses streptogramins
VRE (faecium) only
major adverse effect streptogramins
venous irritation when administered through peripheral vein.
