Abx Mechanism of Resistance Flashcards
Beta-lactams
Production of beta-lactamase (enzyme that inactivates beta-lactams)
-Acquired by plasmid transfer and present in many bacteria (except streptococcus spp.)
-Susceptibility to beta-lactamase varies among each beta-lactam drug, and may possible be overcome by combining a beta-lactam with a beta-lactamase inhibitor.
Alteration of PBPs such that beta-lactams can no longer bind to their target effectively; this form of resistance is d/t mutation of bacterial DNA and may be overcome in some cases by increasing the concentration of the beta-lactam at the site of infection.
MRSA is resistant to most beta-lactams d/t acquisition of both of these forms of resistance.
Fluoroquinolones
Mutation of target site (DNA gyrase), preventing fluoroquinolones from binding to target.
Decreased permeability of outer cell wall membrane of G- bacteri.
Production of efflux proteins that actively transport fluoroquinolones out of bacteria.
Macrolides and Ketolides
Alteration of macrolide target (50S ribosomal subunit) by bacterial enzymes or drug efflux by an active pump
Aminoglycosides
Inactivation of aminoglycosides due to metabolism by enzymes produced in bacteria
Glycopeptides
Mutation of D-ala-D-ala binding site such that vanc. can no longer bind to cell wall precursors
Cyclic lipopeptides
Not well defined.
Likely d/t alteration of membrane potential, which causes reduced binding of daptomycin
Oxazolidinones
Mutation in the 23S subunit
Streptogramins
Mutation of the 50S subunit
Tetracyclines and Glycylcyclines
Modification of the 30S subunit and efflux pump
Nitroimidazoles
Lack of nitroreductase
Lincosamides
Methylation of the 50S subunit
Folate antagonists
TMP: mutation of dihydrofolate reductase (DHFR)
SMX: overproduction of dihydropteroate synthetase; active efflux of sulfonamides out of bacteria
