60+61 - Antimicrobial Resistance III and IV Flashcards
How is metronidazole targeted to pathogens?
Must be reduced to be activated (nitroreductase).
Anaerobic microbes have a lot of reductases to remove oxygen from environment.
How can disc susceptibility break points be determined?
Have to use MIC from dilution tests to construct a curve.
Curve has diameters of inhibition on one axis, MICs from dilutions on the other.
Worst thing to do when prescribing antimicrobials
Prescribe one when one isn’t needed
Considerations when prescribing antimicrobials empirically (best-guess prescription) 1) 2) 3) 4) 5) 6) 7)
1) Is treatment with an antimicrobial needed?
2) Is it safe and reasonable to wait before treating?
3) Are diagnostic samples needed?
4) If so, have they been collected?
5) What is the likely aetiological agent?
6) What is its antimicrobial susceptibility?
7) Is there evidence that treatment will benefit the patient?
Definition of extensively drug-resistant TB (XDR-TB)
Resistant to all four front-line antimicrobials
What are hypervirulent C. difficile strains?
Increased toxin secreiton, antimicrobial resistance
Antimicrobial that all G- bacteria are resistant to
Vancomycin
Method of horizontal gene transfer that can occur between unrelated bacteria
Conjugation
Do bacteria need to be closely-related for transduction to occur?
Yes
Genome of most bacteriophages
dsDNA
Examples of phage-encoded toxins
DIphtheriatoxin, shigatoxin, choleratoxin
Stages of bacteriophage lifecycle
1)
2)
1) Temperate (lysogenic) - Infected with phage, express new phenotype, but bacterium is unharmed
2) Lytic - Phage begins replicating, lyses host
Most-resistant bacteria known
Commensals (EG: S. epidermitis)
Why is most TB resistance from mutation?
Thick cell wall is an impediment to transduction, conjugation
Example of antagonistic antimicrobial combination
Tetracycline and penicillin.
Penicillin only affects actively-growing bacteria. Tetracycline prevents bacterial growth.
Examples of synergistic antimicrobial combination
Beta lactams and aminoglycosides.
Amoxycillin and clavulanic acid
Sulphonamides and trimethoprim
Mechanisms of synergy
1)
2)
3)
1) Inhibit sequential steps in a metabolic pathway (sulphonamides and trimethoprim)
2) Inhibit enzymatic degradation (amoxycillin and clavulanic acid)
3) Enhance antimicrobial uptake by target cell (beta lactams and aminoglycosides)
Mechanisms of antagonism 1) 2) 3) 4)
1) Inhibition of bactericidal activity by bacteriostatic agent
2) Induction of enzymatic degradation
3) Competition for binding of the same target
4) Inhibition of target
Example of antimicrobial antagonistic induction of enzymatic degradation
Ampicillin and piperacillin.
Ampicillin is a strong inducer of beta lactamases, and piperacillin only weakly induces beta lactamases. If administered together, ampicillin induces beta-lactamases which degrade both antimicrobials.
Example of antimicrobials that are theoretically antagonistic, but are synergistic in practise.
Polyenes and imidazole