MOR Flashcards
MOR of beta lactams
destruction of beta lactamase enzymes, alteration of PBPs, and decreased permeability of outer cell membrane in gm - bacteria
MOR of vancomycin
VRE and VRSA: due to modification of D-Ala-D-Ala binding site by expression of vanA (to d-lactate), which prevents the binding of vanc to bacteria
VISA: due to thickening of the peptidoglycan layer of the cell wall, restricting access of vanc into its site of activity
MOR of Synercid
alteration of ribosomal binding site, due to picking up the erm gene, which wipes out ALL drugs that bind to the 50S ribosomal subunit
MOR of oxazolidinones
alteration of ribosomal subunit target site (rare) and cross resistance between linezolid and tedizolid
MOR of daptomycin
rarely reported; altered cell membrane binding through loss of a membrane protein
MOR of lipoglycopeptides
same as vanc, except only affects tela and dalbavancin. oritavancin still maintains activity
MOR of FQs
alteration of binding sites lead to decreased binding affinity of the FQs, expression of active efflux, and alteration in cell wall permeability that doesn’t allow FQ to get into the porins and leads to decreased FQ accumulation within the cell (esp pseudomonas!); cross resistance between FQs
MOR of macrolides
active efflux (mef gene): pumps out of cells and confers low level resistance to macrolides; alteration in the binding site: (erm gene) erm codes for methylation of the macrolide 50S binding site, which leads to low-affinity binding of macrolides (high level resistance to ALL macrolides AND clinda and synercid that bind to 50S subunit)
cross resistance between macrolides also occurs
MOR of aminoglycosides
alteration in aminoglycoside uptake: leads to decreased penetration of aminoglycoside inside bacteria
synthesis of aminoglycoside-modifying enzymes: modified aminoglycoside displays poor uptake through the outer membrane and binds poorly to ribosomes (high level resistance)
alteration in ribosomal binding site (rare)
MOR of tetracyclines
- decreased accumulation of tetracycline within bacteria due to altered permeability or the presence of efflux pumps (that pump away from 30S)
- decreased access of the tetracycline to the ribosome due to the presence of ribosomal protection proteins
- enzymatic inactivation of the tetracycline
- cross resistance between tetracyclines (except minocycline)
what tetracycline can maintain susceptibility against organisms of resistance?
minocycline
what lipoglycopeptide can maintain susceptibility against organisms of resistance?
oritavancin
MOR of tetracycline analogues
retain activity against many tetracycline resistant bacteria because they do NOT appear to be affected by the 2 major tetracycline resistance mechanisms (efflux and ribosomal protection); they can still be resisted due to enzymatic inactivation of tetracycline
MOR of Bactrim
- bacterial resistance is mediated by point mutations in dihydropteroate synthase and/or altered production oro sensitivity of bacterial dihydrofolate reductase
- resistance appears more slowly in combo product
- resistance has been reported in ecoli, h flu, staph
MOR of polymyxins
alteration of outer cell membrane: decreased lipopolysaccharide content, reduction in calcium and magnesium content, decreased outer membrane proteins
cross resistance between polymyxin B and colistin!