Mechanism of Antibiotic Resistance Flashcards
What are problems with empiric therapy?
- Risk of under-treatment
- Risk of excessively broad-spectrum treatment
What are problems with target therapy?
- Expensive
- Last line
- Toxic
What are the reasons for sensitivity testing?
- Explain treatment failures
- Provide alternative antibiotics in case of intolerance/adverse effects, failure
- Provide alternative oral antibiotics when IV therapy no longer required
- Enable transition from empiric to targeted antibiotic therapy
What is the basic principle of sensitivity testing?
- Culture micro-organism in presence of antimicrobial agent
- Determine whether MIC is above predetermined breakpoint level
What are the uses & limitations of sensitivity testing?
- Infection may not be caused by the organism being tested
- Correlation b/ween antimicrobial sensitivity & clinical response is not absolute
- Certain organisms clinically resistant to antimicrobial agents
What are the principles of antibiotic resistance?
- No target
- Reduced permeability
- Altered target
- Over-expression of target
- Enzymatic degradation
- Efflux pump
What antibacterial agents are likely to show an absent target?
-Fungi
-Viruses
(infection which is non-bacterial)
Which bacterial agents are likely to show reduced permeability?
- Gram -ve bacilli (outer layer impermeable to vancomycin)
- Anaerobic organisms (uptake of amino glycoside requires O2 dependent active transport mechanism)
Which bacterial agents are likely to show an alteration in their target?
- MRSA (altered penicillin-binding protein, doesn’t bind B-lactams-flucloxacillin)
- VRE (altered peptide sequence in gram +ve peptidoglycan, vancomycin not effective)
- Gram -ve bacilli (mutations in dhr gene, trimethoprim ineffective)
Which antibiotics are likely to be ineffective with enzymatic degradation?
- Penicillins & cephalosporins by B-lactamases
- Gentamicin by amino glycoside modifying enzyme
- Chloramphenicol by chloramphenicol acetyltransferase (CAT)
Which antibiotics and by what is drug efflux most likely?
- Multiple antibiotics
- Specially by gram -ve organisms
- Antifungal triazoles & candida
What are resistance genes?
- Mechanisms encoded by single genes
- Antibiotic-modifying enzymes (B-lactamases, aminoglycoside modifying enzyme)
- Altered antibiotic target (penicillin-binding protein 2, peptide sequence in peptidoglycan)
Describe resistance genes in plasmids
Circular DNA sequences transmitted within/between species mainly by conjugation
Describe horizontal transfer of resistance
- Enabled by transposons & interns
- DNA sequence designed to be transferred from plasmid to plasmid and/or to chromosome
- Cassettes with multiple resistance genes
Describe vertical transfer of resistance
Chromosomal/plasmid-borne resistance genes transferred to daughter cells on bacterial cell-division
