L58 & 60 Antimicrobial resistance Flashcards
(25 cards)
Name groups of antibiotics that act on the cell wall of a bacteria. (2)
- beta-lactams (e.g. penicillins, cephalosporins)
2. glycopeptides (e.g. vancomycin)
Name the group of antibiotics that disrups the outer membrane of a bacteria and cause leakage of intracellular contents and bacterial death.
Polymyxins (e.g. Colistin. Polymyxin B..)
Daptomycin: Cytoplasmic membrane (not imp)
Name the groups of antibiotics that act on ribosomes of a bacteria (3).
- Aminoglycosides (e.g. gentamicin, amikacin, streptomycin)
- Tetracyclines (e.g. doxycycline, tigecycline…)
- Macrolides (e.g. erythromycin, clarithromycin, azithromycin)
Name the groups of antibiotics that act on chromones of a bacteria (2).
- Quinolones (e.g. ciprofloxacin, levofloxacin, moxifloxacin…)
- Co-trimoxazole (Septra® (containing Sulfamethoxazole, Trimethoprim)
Mechanism of action of beta lactams?
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
What are the 4 mechanisms of beta-lactams resistance? Describe how they work. (8)
- Decreased permeability
- presence of lower permeatbility outer-membrane in GN, - loss of porin channels in outer membrane > beta lactams cannot enter - Efflux pump
- reverse transporting system
- active ejection of Abx
- chromosomal mediated - 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. - Enzymatic activation (to destroy beta-lactam structure)
- beta-lactamase > break beta lactams
What is MRSA?
(methicillin resistance in S.aureus) - mecA gene codes for a different PBP = modification of target site
Give an example of beta-lactam resistance due to presence of a low permeability outer-membrane in GN.
Pseudomonas aeruginosa: intrinsic resistance to many beta-lactams
Give example of beta-lactamase production - enzymatic inactivation in beta-lactams resistance. (2)
- Cefotaxime»_space;> CTX (enzyme) in ESBL (extended spectrum beta-lactamase)
- Carbapenem»_space;> NDM-1 in NDM (New Delhi Metallo-beta-lactamase-1)
Mechanism of action of glycopeptides? e.g. Vancomycin?
- binds to D-ala-D-alanine tail to prevent cell wall formation
Mechanism of glycopeptide resistance?
- Alternation of target that vancomycin inhibits,
e. .g VanA and VanB enterococci are transferable, vancomycin resistant.
Where does Polymycin binds to?
LPS (lipopolysaccarides) and phospholipids in the outer cell membrane of GN bacteria.
There is minimal resistance to polymicin nowadays, and is still useful. Briefly describe one of the resistance of polymicin.
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
Mechanism of Tetracyclines (e.g. doxycycline, tigecycline) and resistance mechanism? (3)
Tetracyclines
- reversible binding to 30S subunit > prevent tRNA binding
Resistance:
- From ribosome protection proteins
- Efflux pump
- Enzymatic modification
Mechanism of aminoglycosides (e.g. gentamicin, amikacin, streptomycin) (2) and resistance mechanism? (2)
Aminocglycosides (30S subunit)
- mis-read mRNA
- Incomplete /absent protein synthsis
Resistance:
- Aminoglycoside modifying enzymes (AME) (~ beta lactamase)
- mutation of ribosomal gene
Mechanism of Linezolid (2) and resistance mechanism (1)?
Linezolid:
- protein synthesis inhibitor
- block initiation of protein synthesis (50S subunit)
Resistance
- mutation of 23S subunit
Mechanism of macrolides (2) (e.g. erythromycin, clarithromycin, azithromycin) and resistance mechanism (1)?
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
Cotrimoxazole (Septrin - Trimethoprim/Sulfamethoxazole) - Mechanism of action? (1)
Resistance mechanism? (3)
MOA: inhibit folate synthesis
Resistance
Mutations in synthase gene!»_space;>
1. reduced permeability
2. increased efflux
Fluoroquinolones (e.g. ciprofloxacin, levofloxacin, moxifloxacin…)
MOA (1)
Resistance mechanism? (1)
MOA:
Inhibit DNA synthesis by inhibitng DNA gyase and toposomerase IV
Resistance
* Point mutation in QRDR (quinolone resistant determining region (gyrA, parC)
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.
- Spontaneous: rare, except rifampicin (point mutation in rpoB gene)
- Induced: AmpC beta-lactamase induced by cephalosporins > resistance
For extrachromosal resistance, it can either be vertical gene transfer (during clonal expansion), or horizontal.
Resistance genes are carried on ____________, list 4 examples.
Mobile genetic elements
1. Plasmid
(auto-replicating DNA sequeces with functional genes) (most common)
- Transposons
(“jumping genes”, mobile from plasmid-to-plasmid, plasmid-to-chromosome…> cut-and-paste/copy-and-paste) - Insertion sequences
(disrupt genome sequences, inserts into chromosome) - Bacteriophages
Other than carrying resistance genes on mobile genetic elements, they can be transferred to others via? (4)
- Transformation
- transfer free DNA segments from dying bacteria - Transduction
- transfer of genes by bacteriophge - Conjugation
- transfer of genes by physical content - Transposition
- specialised DNA seuences that possess transposases to “jump” from 1 location to other
Infection control is crucial in controlling antimicrobial resistance. List examples.
- Hand hygiene
- Rational antibiotic use (narrow spectrum, aquedate dose and duration, compliance, education…)
- Active surveillence in high risk groups
- Patient isolation and/or decontamination
Clavulanate, Sulbactam, Tazobactam are all?
beta-lactamse inhibitors
