Antimicrobial Resistance-Pumerantz

Question 1

What is intrinsic resistance?

Answer 1

Non-enzymatic resistance from nature/genes

Ex: enterococci are intrinsically tolerant to PCN

Question 2

What do G- bacteria have that can block antimicrobials?

Answer 2

Outer membrane, periplasmic space and lipid bilayer

Question 3

Hydrophilic pathway

Answer 3

Only small and hydrophilic molecules can pass thru the porins in the outer membrane
Ex: ampicillin passes thru, vancomycin is too big

Question 4

Hydrophobic pathway

Answer 4

FQs pass directly thru the outer membrane

Question 5

What charge does the periplasmic space carry and why does it matter?

Answer 5

Has negative charge and repels negatively charged antibiotics (cefazolin). Positively charged drugs (aminoglycosides) pass thru

Question 6

What is the inner membrane permeability dictated by and why does it matter?

Answer 6

Transport via electrochemical gradient

Ex: Gentamicin can travel thru membrane in aerobes (Pseudomonas) but not thru anaerobes (bacteroides)

Question 7

What is acquired resistance?

Answer 7

Everything to do with genetics (transmission of modification of genome)

Question 8

What are some enzymatic inactivations?

Answer 8

1. Acetyl-transferases
2. Aminoglycoside-modifying enzymes
3. β-lactamases

Question 9

What is suicidal β-lactam inhibition?

Answer 9

Throw one drug in that will get eaten up by the beta-lactamases while the other drug will produce effect
Ex: Tazobactam and Piperacillin

Question 10

What are Class C β-lactamases?

Answer 10

• Chromosomally induced
• More resistant
• Antibiotic induces formation of peptides that increase transcription of AmpC (cephalosporinase

Question 11

What are Class B β-lactamases?

Answer 11

• Zinc metallo enzyme

* Resistant to PCNS, cephalosporins, carbapenems, aminoglycosides, and FQs

Question 12

Classes of PCNases

Answer 12

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

Question 13

Efflux pumps

Answer 13

Shown in pseudomonas and useful against Tetracyclines

Question 14

Which Tetracycline cannot be pumped out of staph and enterobacteria?

Answer 14

Tigecycline

Question 15

Acinetobacter baumannii

Answer 15

Acquire resistance in big gulps of genes: Efflux pumps, alter PBP, slow Omp channels, β-lactamases and 16s rRNA methylase alteration

Question 16

Bypass inhibited process

Answer 16

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

Question 17

Target alteration

Answer 17

• 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

Question 18

MRSA

Answer 18

• 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

Question 19

Vancomycin

Answer 19

Binds to D-ala-D-ala molecule and blocks the final step in cross-linking

Question 20

Daptomycin

Answer 20

• 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

Question 21

VISA strains

Answer 21

Have gene VanA which makes it resistant to vancomycin and daptomycin

Question 22

Mechanism of Oxacillin resistance

Answer 22

= methicillin resistance

PBP2A conferred by MecA

Question 23

Mechanism of Erythromycin resistance

Answer 23

erm (methylates a ribosome so can’t bind w/macrolide)

Question 24

Mechanism of Tetracycline resistance

Answer 24

Efflux pump (Tigecycline susceptible) OR ribosomal alteration (Tigecycline resistant)

Question 25

Mechanism of PCN resistance

Answer 25

PCNase (oxacillin susceptible) OR PBP2A from MecA (oxacillin resistant)