AST and bacterial mechanisms of resistance

Question 1

Discuss the difference in cell structure of gram positives vs gram negatives

Answer 1

Gram positive - PBPs in plasma membrane
Gram negative - ABs need to reach periplasmic space

Question 2

What are the broad mechanisms of action of antibiotics?

Answer 2

1. Disruption of cell wall synthesis
2. Effects on cell membrane integrity
3. Inhibition of protein synthesis
4. Interference with nucleic acid metabolism
5. Inhibition of enzymes that synthesise folic acid

Question 3

Which antibiotics work on the cell wall?

Answer 3

Beta lactase
Bacitracin

Question 4

Which antibiotics work on cell membrane?

Answer 4

Ampho B
Nystatin
Colistin
Clotrimazole
Ketoconazole

Question 5

Which antibiotics work on nucleic acids?

Answer 5

Quinolones
Rifampin
Flucytosine

Question 6

Which antibiotics work on antimetabolites?

Answer 6

Sulfonamides
Trimethoprim
Ethambutol
Isoniazid

Question 7

Which antibiotics work on protein synthesis?

Answer 7

Tetracyclines
Aminoglycosides
Erythromycin
Chloramphenicol

Question 8

What is the value of mechanism of resistance data?

Answer 8

1. Local epidemiology
2. Antibiotic therapy selection
3. Outbreak detection
4. Unusual AST detection and troubleshooting
5. Design of new drugs

Question 9

What are the kinds of mechanisms of resistance?

Answer 9

1. Antibiotic modification
2. Target modification
3. Target access restriction
4. Efflux pumps

Question 10

Give examples of chromosomal beta lactamases

Answer 10

SHV (klebs pneumonia- ampicillin)
AmpC (e. cloacae)

Question 11

Give examples of plasmid mediated beta lactamases

Answer 11

Penicillinases
Cephalosporinase
Carbapenemase

Question 12

Which gene is common in ESBLs?

Answer 12

CTX - M

Question 13

Name weak ampC inducers

Answer 13

Piptaz
Cefepim

Question 14

Give examples of oxacillinases

Answer 14

OXA-48 (enterobacterales)
OXA-23 (a.baumanii)

Question 15

Which antibiotic is useful in OXA-23s?

Answer 15

Sulbactam-durlobactam

Question 16

Which carbapenemase groups is durlobactam effective against?

Answer 16

A, C, D

Question 17

Name the MBLs

Answer 17

NDM
VIM
IMP

Question 18

Which antibiotic is used in MBLs?

Answer 18

Aztreonam (not stable against ESBLs)

Question 19

Which carbapenemase class are MBLs?

Answer 19

B

Question 20

Which class is varbobactam/relebactam effective against?

Answer 20

Class A

Question 21

Which class does KPC belong to?

Answer 21

Class A

Question 22

What is the most important of the 4 amino glycoside resistance mechanisms and why?

Answer 22

Aminoglycoside modifying enzymes (AMEs)
Frequency and level of resistance

Question 23

In which organisms are altered PBPs more common?

Answer 23

Gram positive

Question 24

Which gene in staph aureus codes for PBP2A to confer cloxacilin resistance?

Answer 24

mecA

Question 25

What is the resistance mechanism in VREs?

Answer 25

Altered cell wall precursors

Question 26

What is the usual mechanism of aciba resistance to colistin?

Answer 26

Chromosomal
Altered lipopolysaccharide with reduced cell membrane negative charge

Question 27

What is the usual mechanism of enterobacterale resistance to colistin?

Answer 27

Plasmid
mcr genes which code enzymes to cause modified lipid A in LPS

Question 28

In which organism is porin loss an important mechanism?

Answer 28

Pseudomonas aeruginosa

Question 29

What is the MOA of cefiderocol?

Answer 29

Enters bacterial cells using active iron transporters

Question 30

What is the usual resistance mechanism to tigecycline?

Answer 30

1. Efflux pump
2. Ribosome modification

Question 31

Which enzyme is modified in s.aureus to confer quinolone resistance?

Answer 31

Topoisomerase IV

Question 32

Which enzyme is modified in p. aeruginosa to confer quinolone resistance?

Answer 32

DNA gyrase