L58 & 60 Antimicrobial resistance Flashcards

1
Q

Name groups of antibiotics that act on the cell wall of a bacteria. (2)

A
  1. beta-lactams (e.g. penicillins, cephalosporins)

2. glycopeptides (e.g. vancomycin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name the group of antibiotics that disrups the outer membrane of a bacteria and cause leakage of intracellular contents and bacterial death.

A

Polymyxins (e.g. Colistin. Polymyxin B..)

Daptomycin: Cytoplasmic membrane (not imp)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Name the groups of antibiotics that act on ribosomes of a bacteria (3).

A
  1. Aminoglycosides (e.g. gentamicin, amikacin, streptomycin)
  2. Tetracyclines (e.g. doxycycline, tigecycline…)
  3. Macrolides (e.g. erythromycin, clarithromycin, azithromycin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name the groups of antibiotics that act on chromones of a bacteria (2).

A
  1. Quinolones (e.g. ciprofloxacin, levofloxacin, moxifloxacin…)
  2. Co-trimoxazole (Septra® (containing Sulfamethoxazole, Trimethoprim)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Mechanism of action of beta lactams?

A

Transpeptidase (penicillin binding protein)on bacterial wall binds to beta lactams instead of D-Ala-D-Ala residual
> inhibit transpeptidation to peptidoglycan
> inhibit cell wall synthesis

*Beta lactams mimic D-ala-D-ala residue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the 4 mechanisms of beta-lactams resistance? Describe how they work. (8)

A
  1. Decreased permeability
    - presence of lower permeatbility outer-membrane in GN, - loss of porin channels in outer membrane > beta lactams cannot enter
  2. Efflux pump
    - reverse transporting system
    - active ejection of Abx
    - chromosomal mediated
  3. Modification of target site
    - PCN-binding protein (=transpeptidase) alteration
    - decreased binding affinity for beta-lactams
    - MRSA (methicillin resistance in S.aureus) - mecA gene codes for a different PBP.
  4. Enzymatic activation (to destroy beta-lactam structure)
    - beta-lactamase > break beta lactams
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is MRSA?

A

(methicillin resistance in S.aureus) - mecA gene codes for a different PBP = modification of target site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Give an example of beta-lactam resistance due to presence of a low permeability outer-membrane in GN.

A

Pseudomonas aeruginosa: intrinsic resistance to many beta-lactams

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Give example of beta-lactamase production - enzymatic inactivation in beta-lactams resistance. (2)

A
  1. Cefotaxime&raquo_space;> CTX (enzyme) in ESBL (extended spectrum beta-lactamase)
  2. Carbapenem&raquo_space;> NDM-1 in NDM (New Delhi Metallo-beta-lactamase-1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mechanism of action of glycopeptides? e.g. Vancomycin?

A
  • binds to D-ala-D-alanine tail to prevent cell wall formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Mechanism of glycopeptide resistance?

A
  • Alternation of target that vancomycin inhibits,

e. .g VanA and VanB enterococci are transferable, vancomycin resistant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where does Polymycin binds to?

A

LPS (lipopolysaccarides) and phospholipids in the outer cell membrane of GN bacteria.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

There is minimal resistance to polymicin nowadays, and is still useful. Briefly describe one of the resistance of polymicin.

A

Mobile Colistin Resistant 1 (MCR-1)
- produce phosphoethanolamine (pEtN) to neutralize -ve charge of LPS > making it +ve to polymycin thus polymycin is not attracted to it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mechanism of Tetracyclines (e.g. doxycycline, tigecycline) and resistance mechanism? (3)

A

Tetracyclines
- reversible binding to 30S subunit > prevent tRNA binding

Resistance:

  • From ribosome protection proteins
  • Efflux pump
  • Enzymatic modification
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mechanism of aminoglycosides (e.g. gentamicin, amikacin, streptomycin) (2) and resistance mechanism? (2)

A

Aminocglycosides (30S subunit)

  • mis-read mRNA
  • Incomplete /absent protein synthsis

Resistance:

  • Aminoglycoside modifying enzymes (AME) (~ beta lactamase)
  • mutation of ribosomal gene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mechanism of Linezolid (2) and resistance mechanism (1)?

A

Linezolid:

  • protein synthesis inhibitor
  • block initiation of protein synthesis (50S subunit)

Resistance
- mutation of 23S subunit

17
Q

Mechanism of macrolides (2) (e.g. erythromycin, clarithromycin, azithromycin) and resistance mechanism (1)?

A

Macrolides

  • block chain elongation by blocking transpeptidation and translocation reactions,
  • block formation of 50S protein too

Resistance:
- erm - a resistant gene causing Erythromycin ribosome methylation

18
Q

Cotrimoxazole (Septrin - Trimethoprim/Sulfamethoxazole) - Mechanism of action? (1)
Resistance mechanism? (3)

A

MOA: inhibit folate synthesis

Resistance
Mutations in synthase gene!&raquo_space;>
1. reduced permeability
2. increased efflux

19
Q

Fluoroquinolones (e.g. ciprofloxacin, levofloxacin, moxifloxacin…)
MOA (1)
Resistance mechanism? (1)

A

MOA:
Inhibit DNA synthesis by inhibitng DNA gyase and toposomerase IV

Resistance
* Point mutation in QRDR (quinolone resistant determining region (gyrA, parC)

20
Q

Aquisition of antimicrobial resistance can be divided into chromosomal resistance and extrachronosomal resistance.
For chromosomal resistance, it can be spontaneous or induced. Give examples for each.

A
  • Spontaneous: rare, except rifampicin (point mutation in rpoB gene)
  • Induced: AmpC beta-lactamase induced by cephalosporins > resistance
21
Q

For extrachromosal resistance, it can either be vertical gene transfer (during clonal expansion), or horizontal.

Resistance genes are carried on ____________, list 4 examples.

A

Mobile genetic elements
1. Plasmid
(auto-replicating DNA sequeces with functional genes) (most common)

  1. Transposons
    (“jumping genes”, mobile from plasmid-to-plasmid, plasmid-to-chromosome…> cut-and-paste/copy-and-paste)
  2. Insertion sequences
    (disrupt genome sequences, inserts into chromosome)
  3. Bacteriophages
22
Q

Other than carrying resistance genes on mobile genetic elements, they can be transferred to others via? (4)

A
  1. Transformation
    - transfer free DNA segments from dying bacteria
  2. Transduction
    - transfer of genes by bacteriophge
  3. Conjugation
    - transfer of genes by physical content
  4. Transposition
    - specialised DNA seuences that possess transposases to “jump” from 1 location to other
23
Q

Infection control is crucial in controlling antimicrobial resistance. List examples.

A
  • Hand hygiene
  • Rational antibiotic use (narrow spectrum, aquedate dose and duration, compliance, education…)
  • Active surveillence in high risk groups
  • Patient isolation and/or decontamination
24
Q

Clavulanate, Sulbactam, Tazobactam are all?

A

beta-lactamse inhibitors

25
Q

Multidrug resistance organisms (MDRO) are those which are resistant to 3 or more of the 8 classes of Abx
(BL/BLI, anti-pseudomonal cephalosporins, carbapenems, aztreonam, FQ, AG, tigecycline, polymyxin E).

How about Extensive drug resistance (XDR)
and Pandrug resistance (PDR)?

A

Extensive drug resistance (XDR): susceptible to 2 or less classes;

Pandrug resistance (PDR): diminished susceptibility to all classes.