3- Antibiotic Resistance Flashcards Preview

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Flashcards in 3- Antibiotic Resistance Deck (22)
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1
Q

What is the Minimal Inhibitory Concentration (MIC)

A

= the lowest concentration of the

antibiotic required to inhibit growth

2
Q

What is the breakpoint?

A

Breakpoint = an estimate of the reasonable concentration that might be achieved clinically
Any organism that can grow at a concentration of the breakpoint or
greater than the breakpoint is resistant

3
Q

•Give some gram negative MAJOR ANTIBIOTIC RESISTANT BACTERIAL PATHOGENS

A
Pseudomonas aeruginosa
E. coli (ESBL)
Klebsiella spp. (NDM-1)
Salmonella spp. (MDR) 
Acinetobacter baumannii (MDRAB) 
Neisseria gonorrhoeae
4
Q

Give some grampositive MAJOR ANTIBIOTIC RESISTANT BACTERIAL PATHOGENS

A
Staphylococcus aureus (MRSA, VISA) Streptococcus pneumoniae
Clostridium difficile
Enterococcus spp (VRE)
Mycobacterium tuberculosis (MDRTB, XDRTB)
5
Q

How do beta lactams work?

A

Interfere with synthesis of the PEPTIDOGLYCAN component of the bacterial cell wall
• Examples: Penicillin and methicillin
• Binds to Penicillin Binding Proteins (PBP) - they catalyse a number of steps in a large peptidoglycan synthesis
• The beta-lactam ring is similar in structure to a precursor of peptidoglycan - interferes with the biosynthetic pathway of peptidoglycan
NOTE: MRSA has a different PBP (PBP2a) which doesn’t bind with high affinity to beta-lactams

6
Q

How does tetracycline work?

A
Bacteriostatic
• Inhibits PROTEIN SYNTHESIS
• Binds to the 16S component of the
30S ribosomal subunit thus
preventing charged aminoacyl tRNAs from binding to the mRNA/ribosome complex
• Prevents elongation of the polypeptide
7
Q

How does chloramphenicol work?

A

Bacteriostatic
• Inhibits PROTEIN SYNTHESIS
• Binds to 50S subunit and blocks peptidyl transfer step
• Often used topically due to toxicity

8
Q

How do quinolones work?

A

Targets DNA gyrase (in Gram NEGATIVE) and topoisomerase (in Gram POSITIVE)
• DNA gyrase and topoisomerase is responsible for unravelling DNA

9
Q

How do sulphonamides work?

A

Bacteriostatic
• Used to treat UTI, Reproductive Tract Infection (RTI) and bacteraemia
• Interferes with the folate pathway

10
Q

How do aminoglycocides work?

A

• Bactericidal
• EXAMPLES: Gentamycin, Streptomycin
• Affect PROTEIN SYNTHESIS
• Affects RNA PROOFREADING which leads to misfolded proteins
• Some of these proteins are incorporated into the membrane and allow leakage
so the cells rupture.
• Has toxicity issues

11
Q

How do macrolides work?

A

EXAMPLE: Erythromycin
• Gram POSITIVE infections
Targets 50S ribosomal subunit preventing aminoacyl transfer
• Causes truncation of polypeptides

12
Q

What are the mechanisms of antibiotic resistance?

A

Altered Target Site
• Inactivation of Antibiotic
• Altered Metabolism
• Decreased Drug Accumulation

13
Q

Describe altered target site

A

Can arise from acquisition of an alternative gene or a gene that encodes a target-modifying enzyme
• You can acquire a gene, which performs the same function but has a different structure and hence is not susceptible to the AB.
• EXAMPLE: MRSA acquired a gene, which produces an alternative penicillin binding protein - it performs the same function but has lower affinity to beta- lactams so methicillin is ineffective.
• Streptococcus pneumoniae is resistant to erythromycin because it has acquired a gene which encodes an enzyme that methylates the AB target site in the 50S ribosomal subunit - this changes its structure so erythromycin can no longer act

14
Q

Describe inactivation of an antibiotic

A

Acquire gene for an enzyme which breaks down the antibiotic
• EXAMPLES: beta-lactamase (bla) and chloramphenicol acetyl-transferase (cat)
• ESBL and NDM-1 are examples of broad spectrum beta-lactamases

15
Q

Describe altered metabolism

A

Re-engineer the metabolic pathways so you bypass the step that the antibiotic interferes with.
• Increased production of enzyme substrate can be used to outcompete antibiotic inhibitor
EXAMPLE: increased production of PABA confers resistance to sulphonamides

16
Q

Describe decreased drug accumulation

A

Reduced permeability of AB into bacterial cell
• Increase EFFLUX of AB out of cell or reduce penetrance
• Drug does not reach sufficient concentration to be effective

17
Q

What are 3 Sources of AB resistance genes:

A

Plasmids Transposons Naked DNA

18
Q

Why also might an antibiotic not work?

A

Inappropriate choice of organism
• Poor penetration of AB into target site
• Inappropriate dose
Inappropriate administration
• Presence of AB resistance within commensal flora e.g. secretion of beta-lactamase

19
Q

What are risk factors for HAI?

A

High number of ill people! (immunosuppression)
Crowded wards
Presence of pathogens
Broken skin – surgical wound/IV catheter Indwelling devices - intubation
AB therapy may suppress normal flora
Transmission by staff – contact with multiple patients

20
Q

How can AB resistance be addressed?

A

Tighter controls on prescription
• Reduce use of broad spectrum antibiotics
• Quicker identification of infections caused by resistant strains
• Combination therapy
• Knowledge of local strains/resistance patterns

21
Q

How do different AB become resistant

A

Sulfonamide resistance is conferred by blocking uptake/decreasing influx.
Tetracycline resistance is mediated by efflux/membrane pumps.
Penicillin resistance works via drug inactivation (beta-lactamase) or altered target site (alternative penicillin-binding proteins as found in MRSA).
Metronidazole resistance is associated with with target amplification.
Quinolone by target site modification

22
Q

What are transposons

A

Transposons are sequences of DNA that can move around to different parts of a cell’s genome, carrying with them resistance genes.