Antimicrobial resistance I

Question 1

Mode-of-action

Answer 1

• Cell wall synthesis
• DNA, RNA & protein synthesis
• Folic acid metabolism

Question 2

Classes + representatives + mode-of-action

Question 3

Why is the cell wall a good target for antibiotics?

Answer 3

Human cells don’t have a cell wall

Question 4

What do all the B-lactams have in common structure-wise?

Answer 4

Ringstructure B-lactam

Question 5

What are the members of the beta-lactam family?

Answer 5

• Penicillins
• Cephalosporins
• Carbapenems
• Monobactams

Question 6

What can be said about the structure of the bacterial cell wall of gram-negative bacteria?

Answer 6

Gram-negative bacteria have a very thin layer of peptidoglycan + membrane in- AND out of their cell wall

Question 7

On what structure do beta-lactams work?

Answer 7

Peptidoglycan

Answer 8

• Sugar layer of NAM and NAG (sugar chains)
• Connected via peptide bridges

Question 9

The strength of the peptidoglycan network depends on …

Answer 9

It’s compactness, which itself depends on the length of the polysaccharide chains, the number of tetrapeptide bridges and on any hydrogen bonds that may form.

Question 10

Key enzymes involved in the the peptidoglycan synthesis

Answer 10

Cytoplasm: smaller parts are made –>

Cell surface stage

Question 11

What are the Penicillin Binding Proteins?

Answer 11

• Transglycosylases
• Transpeptidase
• Carboxypeptidases

Question 12

Where are the Penicillin Binding Proteins anchored?

Answer 12

In cytoplasmic membrane

Question 13

Why do beta-lactams kill bacterial cells?

Answer 13

11 min

Question 14

Explain the fragile dynamic balance between synthesis and hydrolysis of PG

Question 15

Lytic enzymes or autolysins

Answer 15

• Glycosidases
• N-acetyl-muramyl-L-alanine amidases
• Endopeptidases

Question 16

On what does the bactericidal effect depend?

Answer 16

lytic enzymes, involved in
breaking down and rearranging PG

Question 17

Beta-lactams work especially on active bacteria

Question 18

Differences in activity among the various β-lactams depends on..

Answer 18

Penetration of the Gram-negative cell
Lability to periplasmic β-lactamases
Affinity to the PBPs

Question 19

Mechanisms of resistance to β-lactam antibiotics (3)

Answer 19

• Impaired permeability of outer membrane
• Mutated PBPs with changed affinity
• Enzymatic hydrolysis of the β-lactam ring

Question 20

Penetration of β-lactams into Gram-negative bacteria

Answer 20

• Passage via porins
• Physicochemical factors influencing penetration

Question 21

What is a porin and what is critical for the activity of B-lactams

Answer 21

-A porin is a transmembrane protein

Speed of diffusion of β-lactams through the porins is critical for their activity

Question 22

Physicochemical factors influencing penetration (3)

Answer 22

-hydrophobicity
-the size of the molecule
-charge

Question 23

Where can the B-lactamase come from?

Answer 23

• Chromosome
• Plasmid

Question 24

What can the expression patterns of B-lactamases orginating from the chromosome?

Answer 24

• Inducible
• Constitutive

Question 25

Example of inducible / phenotype

Answer 25

cephalosporinase

Question 26

Example of constitutive /phenotype for chromosome and plasmids

Answer 26

penicillinase

Question 27

What can the expression patterns of B-lactamases orginating from plasmids?

Answer 27

Constitutive

Question 28

If the enzyme is only effective against penicillin, you can use the other categories

Question 29

Extended spectrum beta-lactamases?

Answer 29

22min

Question 30

SHV-1

Question 31

Why are aminoglycosides suitable for use in humans?

Answer 31

Difference in ribosomal subunits between humans and bacteria

Question 32

Derivatives of micin and mycin

Question 33

Mechanism of aminoglycoside Action

Answer 33

Energy-independent phase Energy-dependent phase Binding to the 30S ribosomal subunit !! (most important for exam)

Question 34

Energy-independent phase

Answer 34

electrostatic binding to the outer membrane

Question 35

Energy-dependent phase

Answer 35

transport into the cytoplasm by PMF (transmembrane electrical potential)

Question 36

Binding to the 30S ribosomal subunit !! (most important for exam)

Answer 36

inhibition of protein synthesis misreading of the codons

Question 37

What does PMF mean?

Question 38

Mechanisms of resistance to aminoglycosides

Answer 38

Aminoglycoside-modifying enzymes (most important!!) Alteration in uptake Change in ribosomal binding sites (methyltransferases)

Question 39

Name the three categories of aminoglycoside-modifying enzymes

Answer 39

AAC: acetyltransferases ANT: adenyltransferases APH: phosphotransferase

Question 40

AAC: acetyltransferases

Answer 40

acetyl CoA-dependent acetylation of an amino group

Question 41

ANT: adenyltransferases

Answer 41

ATP-dependent adenylation of an hydroxyl group

Question 42

APH: phosphotransferase

Answer 42

ATP-dependent phosphorylation of an hydroxyl group

Question 43

DNA: guinolones, why very powerful and widely used?

Answer 43

Many of these can be taken as tablets and are still sufficiently absorbed and bactericidal --> perfect penetration of tissue

Question 44

Uptake of quinolones into the bacterium

Question 45

Mechanism of action of quinolones

Question 46

Role of topoisomerases

Answer 46

- Regulate the super-coiling of DNA. - Cuts dsDNA to initiate replication.

Question 47

Mechanisms of resistance (chromosomally-encoded) quinolones

Answer 47

- Decreased target-affinity - Decreased accumulation

Question 48

Decreased target-affinity

Answer 48

Mutations in DNA-gyrase and topoisomerase IV - Mutations in ‘quinolone resistance-determinating region (QRDR)’

Question 49

Decreased accumulation

Answer 49

- Decreased porine-expression (low-level resistance) - Hyper-expression of natural efflux

Question 50

Mechanisms of resistance (Plasmid-mediated resistance) quinolones

Answer 50

- qnrA - Aminoglycoside acetyltransferase - Quinolone efflux pumps

Question 51

How does qnrA work?

Answer 51

Binds to DNA gyrase and topoisomerase IV, leading to inability for quinolones to bind

Question 52

Patient being hospitalized abroad have a higher chance of bringing MDROs

Question 53

Prevalence of MDROs

Answer 53

Africa West-Pacific Southern Asia

Question 54

Study protocol

Answer 54

Healthy travelers included via travel clinics 2001 travelers 215 household members Sample kit directly before and after travel Fecal swabs Follow up for 12 months 1, 3, 6 and 12 months after return

Question 55

Risk factors MDRO acquisition

Answer 55

Antibiotic use during travel Traveller’s diarrhoea Meal at street food stalls

Question 56

Protective factors MDRO acquisition

Answer 56

Daily hand washing before meals Beach holidays

Question 57

Leading risk factors for acquisition of MDR-E are

Answer 57

Travel to Southern Asia Antibiotic use during travel Traveller’s diarrhoea

Question 58

Hospitals: unknown carriage could lead to? (3)

Answer 58

- Difficulty treating infections - Hospitalization without the appropriate infection prevention and control measures - Spread to other patients, healthcare personnel and the hospital environment

Question 59

Which division can be made in-hospital (nosocomial) transmission?

Answer 59

- Direct transmission - Indirect transmission

Question 60

How is direct transmission established in the hospital?

Answer 60

Patient-to-patient, patient-to-healthcare personnel

Question 61

How is indirect transmission established in the hospital?

Answer 61

Hospital environment, medical devices

Question 62

What is the current MDRO screening strategy?

Answer 62

Universal risk assessment with risk-based screening