Antimicrobial Resistance-Pumerantz Flashcards
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What is intrinsic resistance?
Non-enzymatic resistance from nature/genes
Ex: enterococci are intrinsically tolerant to PCN
What do G- bacteria have that can block antimicrobials?
Outer membrane, periplasmic space and lipid bilayer
Hydrophilic pathway
Only small and hydrophilic molecules can pass thru the porins in the outer membrane
Ex: ampicillin passes thru, vancomycin is too big
Hydrophobic pathway
FQs pass directly thru the outer membrane
What charge does the periplasmic space carry and why does it matter?
Has negative charge and repels negatively charged antibiotics (cefazolin). Positively charged drugs (aminoglycosides) pass thru
What is the inner membrane permeability dictated by and why does it matter?
Transport via electrochemical gradient
Ex: Gentamicin can travel thru membrane in aerobes (Pseudomonas) but not thru anaerobes (bacteroides)
What is acquired resistance?
Everything to do with genetics (transmission of modification of genome)
What are some enzymatic inactivations?
- Acetyl-transferases
- Aminoglycoside-modifying enzymes
- β-lactamases
What is suicidal β-lactam inhibition?
Throw one drug in that will get eaten up by the beta-lactamases while the other drug will produce effect
Ex: Tazobactam and Piperacillin
What are Class C β-lactamases?
- Chromosomally induced
- More resistant
- Antibiotic induces formation of peptides that increase transcription of AmpC (cephalosporinase
What are Class B β-lactamases?
- Zinc metallo enzyme
* Resistant to PCNS, cephalosporins, carbapenems, aminoglycosides, and FQs
Classes of PCNases
TEM-1 and SHV-1
• Originally passed on by plasmids. Have a serine active site that hydrolyzes the β-lactam ring
• Modify the antibiotic w/ a bulky oximino-side chain close to the β-lactam ring
Efflux pumps
Shown in pseudomonas and useful against Tetracyclines
Which Tetracycline cannot be pumped out of staph and enterobacteria?
Tigecycline
Acinetobacter baumannii
Acquire resistance in big gulps of genes: Efflux pumps, alter PBP, slow Omp channels, β-lactamases and 16s rRNA methylase alteration
Bypass inhibited process
S. aureus can bypass a process that would be inhibited by antibiotics (production of thymidine) and take up free thymidine from dead cells in the surrounding environment
Ex: Trimethoprim and sulfamethoxazole inhibited thymidine production
Target alteration
- Ribosomal methylation which renders macrolides inert
- Inducible erm gene adds 1-2 methyl groups to peptidyl transferase center of 23S rRNA subunit
- If you suspect that the bacteria has this gene, do a D-test
MRSA
- Carried by mecA gene and mediates β-lactam resistance
- Sensor on membrane that senses a β-lactam by mecR1 (homolog of blaR1)
- Ceftaroline has MRSA activity
Vancomycin
Binds to D-ala-D-ala molecule and blocks the final step in cross-linking
Daptomycin
- Has a tail that it inserts into a bacterial cell membrane, causes it to depolarize and die
- VISA continues to thicken their cell wall as the amount of Daptomycin is increased
VISA strains
Have gene VanA which makes it resistant to vancomycin and daptomycin
Mechanism of Oxacillin resistance
= methicillin resistance
PBP2A conferred by MecA
Mechanism of Erythromycin resistance
erm (methylates a ribosome so can’t bind w/macrolide)
Mechanism of Tetracycline resistance
Efflux pump (Tigecycline susceptible) OR ribosomal alteration (Tigecycline resistant)
Mechanism of PCN resistance
PCNase (oxacillin susceptible) OR PBP2A from MecA (oxacillin resistant)
