2 - Mechanisms of antibiotic resistance Flashcards
Empiric therapy definition
A decision made based on experience in the absence of complete data
Targeted therapy definition
Specific drugs for specific problems
Reasons for sensitivity testing
Transition for empiric to targeted
Explains treatment failures
Provides alternate antibiotics in case of failure/adverse effects
Allows oral vs IV
How does a sensitivity test work basically
- Culture microorganism with anti microbe agent (in little wells)
- Determine whether MIC is above breakpoint level
- Seen by how far the antimicrobe agent spreads from well (size of zone of inhibition)
So high enough conc and is present for enough time
Problems with sensitivity test
Infection may not be caused by the tested organism
The correlation is not absolute - to do with likeliness
How do bacteria resist drugs
No target - no effect Reduce their permeability Altered target Over-expression of target (dilutes the effect) Enzymatic degradation (destroys drug) Efflux pump (expels drug)
Examples of reduced permeability
Gram–ve bacilli resist vancomycin because the outer membrane is impermeable
Anaerobic organisms resist gentamicin because aminoglycosides require O2 dependent transport mechanisms
Target alteration
Flucloxacillin - MRSA changed binding proteins
Mostly changing peptide sequences
Enzymatic degration
Penicillins and cephalosporins release B-lactamases
Gentamicin - aminoglycoside modifying enzymes
Drug efflux
Multiple antibiotics especially in gram–ve organisms
Antifungal triazoles and candida
How does antibiotic resistance build
Most resistance from single genes. Can: Makes enzymes Alters antibiotic targets Resistance genes in plasmids (conjugation) Horizontal transfer of resistance Vertical transfer of resistance
Making enzyme for resistance examples:
B-lactamases (from penicillins, cephalosporins)
Aminoglycoside-modifying enzymes (from gentamicin)
Altering antibiotic target examples
(penicillin binding protein in MRSA).
Peptide sequence in VRE peptidoglycan
Resistance gene encoded in plasmids - what are they, what do
Circular DNA sequences transferring within species and, rarely, between species, via conjugation
Horizontal transfer of resistance
Enabled by transposons and integrons
DNA sequences designed to transferred plasmid to plasmid or to chromosomes
Contain cassettes within multiple resistance genes
