antibiotic resistance

Question 1

What do bacteriostatic antibiotics do?

Answer 1

Inhibit bacterial growth by inhibiting protein syntheses, DNA replication and metabolism
Also reduce exotoxin production and endotoxin surge less likely from gram -ve bacteria

Question 2

What do bactericidal antibiotics do?

Answer 2

Inhibit cell wall synthesis causing death of bacteria

Question 3

When are bactericidal antibiotics very useful?

Answer 3

Poor tissue penetration (e.g. Endocarditis)
Difficult to treat infections (e.g. TB)
Need to eradicate infection quickly (e.g. meningitis)

Question 4

What is required for a bacteriostatic antibiotics to work?

Answer 4

Minimum inhibitory concentration (MIC) MIC:MBC ratio >4

Question 5

What is required for bactericidal antibiotics to work?

Answer 5

Minimum bactericidal concentration (MBC)

Question 6

What does concentration dependent killing depend on?

Answer 6

The height of concentration above the minimum inhibitory concentration (MIC)
Peak concentration/MIC ratio

Question 7

What does time dependent killing depend on?

Answer 7

On time the concentration stays above the minimum inhibitory concentration for
t>MIC

Question 8

Give an example of an antibiotic group that uses concentration dependent killing

Answer 8

Aminoglycosides

quinolones

Question 9

Give 2 examples of a antibiotic groups that uses time dependent killing

Answer 9

Beta lactams
Macrolides
clindamycin

Question 10

Name 4 mechanisms of antibiotic resistance

Answer 10

1. target site mutation
2. Destroy or inactivate antibiotic
3. Prevent antibiotic access
4. Remove antibiotic from bacteria

Question 11

how does target site mutation cause antibiotic resistance?

Answer 11

Changes molecular configuration at antibiotic binding site or masks it

Flucloxacillin is no longer able to bind to PBP of Staphylococci in MRSA

Question 12

Give 2 examples of the destroy/inactivate antibiotic mechanism of antibiotic resistance

Answer 12

1. Beta lactamase hydrolyses beta lactam ring so it can no longer bind to PBP
2. Staph producing penicillinase so penicillin but flucloxacillin is inactivated

Question 13

how does removal of antibiotic cause antibiotic resistance?

Answer 13

Export pumps remove the antibiotic so the level of antibiotic is reduced

1. S. aureus and S. pneumoniae resistant to fluoroquinolones
2. Enterobacteriaceae resistance to tetracyclines

Question 14

By what 2 ways can antibiotic resistance develop?

Answer 14

1. Intrinsic (naturally resistant)

2. Acquired

Question 15

Give 3 examples of intrinsic antibiotic resistance development

Answer 15

1. Gram -ve outer membrane can’t be penetrated by vancomycin
2. Enterococci PBP are not effectively bound by cephalosporins
3. Aerobic bacteria enable to reduce metronidazole to its active form

Question 16

what are the 2 ways that acquired antibiotic resistance can occur?

Answer 16

1. Spontaneous mutation

2. Horizontal gene transfer

Question 17

How can acquired spontaneous mutation antibiotic resistance come about?

Answer 17

1. New nucleotide base pair
2. Change in aa sequence
3. Change to enzymes to cell structure
4. Reduced affinity or activity of antibiotic
   Cause altered enzyme function leading to reduced antibiotic effect

Question 18

Give and briefly explain the 3 types of horizontal gene transfer antibiotic resistance

Answer 18

1. Conjugation - sharing of extra-chromosomal DNA plasmids (‘bacteria sex’)
2. Transduction - insertion of DNA by bacteriophages
3. Transformation - bacteria takes up free DNA

Question 19

Name 2 important gram +ve antibiotic resistant organisms

Answer 19

1. Methicillin resistant Staphylococcus Aureus (MRSA)

2. Vancomycin Resistant Enterococci (VRE)

Question 20

How has MRSA gained antibiotic resistance?

Answer 20

1. Staphylococcal cassette chromosome med (SSCmec) contains resistance gene mecA
2. Encode penicillin-binding protein 2a (PBP2a) that does not bind to penicillin
3. Confers resistance to beta lactam antibiotics as well as Methicillin

Question 21

How has vancomycin-resistant enterococci (VRE) gained antibiotic resistance?

Answer 21

Plasmid mediated acquisition of gene encoding altered aa on peptide chain preventing vancomycin binding
Promoted by cephalosporin use

Question 22

Name 3 important gram -ve antibiotic resistant types

Answer 22

1. b-lactamase enzymes hydrolysing penicillins
2. Extended spectrum beta lactamase (ESBL)
3. AmpC b-lactamase resistance

Question 23

Give 3 examples of b-lactamase enzymes hydrolysing penicillins

Answer 23

TEM-1 in E. coli, H. influenzae and N. gonorrhoea

SHV-1 in K. pneumoniae

CTX_M cephalosporinase in enterbacteriaceae

Question 24

What, typically, are b-lactamase enzymes hydrolysing penicillins sill sensitive to?

Answer 24

Extended spectrum beta lactamase (ESBL) inhibitors due to a further mutation at active site

Question 25

What can extended spectrum beta lactamase inhibitors destroy or inactivate?

Answer 25

Penicillin
Amoxycillin
Cephalosporins
Combination antibiotics

Question 26

What can carbapenemases be produced by?

Answer 26

Carbapenemase reistant enterobacteria (CRE)

Question 27

Explain the preventing antibiotic access mechanism of antibiotic resistance

Answer 27

Modify membrane channels - size, number and selectivity

Question 28

Give 2 definitions of antibiotic

Answer 28

Agents produced by microorganism that kill or inhibit the growth of other microorganisms in high dilution

Question 29

What do antimicrobials include?

Answer 29

Antifungal 
Antibacterial 
Antihelminthic
Antiprotozoal
Antiviral