Antibiotic resistance. Flashcards
define antibiotic era
time since the widespread availability of antibiotics to treat infection
define antibiotic era
time after widespread antibiotic resistance has reduced the availability of antibiotics to treat infection
what drugs are enterobactericase resistant to
amoxicillin, ciprofloxacin, gentamicin, carbapenems
what drugs are psuedomonas resistant to
ceftazidime, carbapenems
2 types of therapy for infection treatment
empiric- risk of over of under treatment
Targeted- specific but can be expensive, last line drug or toxic.
why do we test sensitivity
treatment can be more targeted
explain treatment failures
provide alternate antibiotics
Solid media - disk susceptibility testing method
- Add organism
- Add antibiotics
- Incubate
- Read and interpretation results
- Clinical interpretation.
• Size of the zone of inhibition is proportionate to sensitivity of the antibiotic.
Liquid media- disk suceptibilty testing method.
- Put same antibiotic in each well across the row but as you go across each one decrease the concentration by 50%.
- Then add the organism.
- If the organism grows more to the left it is more resistant whereas to the right it is more susceptible.
- Used to determine the accurate MIC value.
Limitations of sensitivity testing
- The infection may not be caused by the organism that has been tested- e.g if you test sputum after antibiotic treatment you may find another bacteria.
- The correlation between antimicrobial sensitivity and clinical response is not absolute
resistant genes with are expressed in vivo but not in virgo
AmpC β-lactamase genes in Enterobacteriaceae
six resistance mechanisms
- No target – no effect
- Reduced permeability – drug can’t get in
- Altered target – no effect
- Over-expression of target – effect diluted
- Enzymatic degradation – drug destroyed
- Efflux pump – drug expelled
Examples of absent target for antimicrobial agent
antibacterial agents used for fungi or virus
Examples of reduced permeability of an antimicorbial agent.
Vancomycin for gram-ve bacteria (gram -ve has outer membrane which cannot be penetrated by vancomycin.
Gentamicin used for anaerobic organisms- aminoglycoslides require O2 dependent active transport mechanisms.
Example of target alteration
Flucloxacillin for MRSA- altered penicillin binding protein does not bind B lactams.
vancomycin for vancomycin resistant enterococci- altered sequence in gram +ve peptidoglycan which reduces its binding.
Trimethoprim- gram negative bacilli- mutations of dihyrdofolate reducatase.
Examples of enzyme degradation
Penicillins and cephalosporins: β-lactamases degrade these antibiotics.
Gentamicin: aminoglycoside modifying enzymes degrade these antibiotics
Chloramphenicol: chloramphenicol acetyltransferase (CAT) degrade these antibiotics.
Examples of drug efflux
Multiple antibiotics, specially in Gram-negative organisms
Antifungal triazoles and Candida spp.
Resistance caused by single genes
Antibiotic-modifying enzymes
- Β-lactamases (including ESBL), Penicillins, cephalosporins. Aminoglycoside-modiying enzymes
- Gentamicin
What is vertical transfer of resistance
Between and organism and it’s own progeny. genes transferred to daughter cells on cell division.
What is horizontal transfer of resistance.
Between 2 organisms
Transporon and integrons are DNA sequences within plasmid. They transfer genes between plasmids.
Often contain “cassettes” with multiple resistance genes
How does Gene transfer happen
- Antibiotic resistance gene on plasmid
- Gene may stay on plasmid and or integrate into chromosome
- Plasmid transferred between organism by conjugation
- Gene may stay on plasmid or integrate into chromosome
- New organism is antibiotic resistance.
- Antibiotic resistance transferred upon cell division.
risks of inappropriate antibiotic exposure
RESISTANCE
- Sensitive strains are exposed at sublethal concentrations.
- Chance of survival will be enhanced by development of resistance.
- Resistant strain will out-compete sensitive strain- – Subsequent endogenous infection more likely to be caused by resistant strains.
- Resistance continued by vertical transfer.
