Hospital acquired infection and antibiotic resistance

Question 1

What is the breakpoint?

Answer 1

The concentration of antibiotic that can be achieved in a clinical setting If the bacteria can divide at a concentration at or higher than the breakpoint, it is deemed resistant

Question 2

Name some major antibiotic resistant Gram-negative bacterial pathogens.

Answer 2

• Pseudomonas aeruginosa
• E.coli
• Klebsiella
• Salmonella
• Acinetobacter baumanii
• Neisseria gonorrheae

Question 3

Name some major antibiotic resistant Gram-positive bacterial pathogens.

Answer 3

-Staphylococcus aureus (MRSA) -Streptococcus pneumoniae -Clostridium dificile -Enterococcus spp. -Mycobacterium tuberculosis

Question 4

Name 7 types of antibiotic.

Answer 4

Beta-lactams Aminoglycosides Chloramphenicol Tetracycline Quinolones Sulphonamides Macrolides

Question 5

How do beta-lactams work?

Give some examples

Answer 5

Penicillin and Methicillin
-Interferes with synthesis of the peptidoglycan componenet of the bacterial cell wall, by binding to penicillin binding proteins- which catalyses a number of steps in peptidoglycan synthesis.

They have a beta-lactam ring that is a similar shape to a precursor of peptidoglycan in the bacterial cell wall and hence interferes with the synthesis of the cell wall

CELL WALL

Question 6

How do aminoglycosides work? Give some examples.

Answer 6

Gentamicin and streptomycin.

• Bactericidal: kills bacteria
• Affects protein synthesis.
• affects RNA proofreading which leasd to misfolded protein Some of these proteins get incorporated into the membrane and cause leakage so cells rupture

Question 7

How does Rifampicin work?

Answer 7

• bactericidal
• targets subunit of RNA polymerase
• makes secretions go orange/red: affects compliance

Question 8

How does vancomycin work?

Answer 8

bactericidal
-targets Lipid II component of cell wall biosynthesis, and wall crosslinking via D-ala residues

CELL WALL

Question 9

How does Linezolid work?

Answer 9

• bacteriostatic
• inhibits the initiation of protein synthesis by binding to 50S rRNA subunit.
• gram-positive spectrum of activity

Question 10

How does daptomycin work?

Answer 10

• bactericidal
• targets bacterial cell membrane
• gram positive specturm
• toxicity limits dose

Question 11

How does tetracycline work?

Answer 11

• bacteriostatic ( stops bacteria growing)
• Prevents charged amino-acyl tRNAs from binding to the mRNA/ribosome complex, so prevents elongation
• binds to 30S subunit

PROTEIN SYNTHESIS

Question 12

How does chloramphenicol work?

Answer 12

Inhibits the peptidyl transfer step Binds to the 50S subunit

PROTEIN SYNTHESIS

Question 13

How do quinolones work?

Answer 13

Quinolones inhibit the functioning of DNA gyrase (Gram-negative) and topoisomerase (Gram-positive) hence hampering the unravelling of DNA during replication

DNA REPLICATION

Question 14

How do macrolides work? Give an example.

Answer 14

Erythromycin.
Only Gram-positive infections and some gram-negative Targets the 50S ribosomal subunit and prevents the aminoacyl transfer, causes truncation

PROTEIN SYNTHESIS

Question 15

How do sulphonamides work?

Answer 15

Bacteriostatic

Inhibits the folate pathway

Question 16

What are the four main mechanisms of antibiotic resistance?

Answer 16

Altered target site: acquire a gene that has same function but different structure
Inactivation of antibiotic :
gene codes for enzyme that kills antibiotic
Altered metabolism: to bypass the step that the antibiotic interferes with/ produce lots of enzymes to out-compete the AB
Decreased drug accumulation: reduce permeability of AB into bacterial cell, so drug doesn’t reach concentration to be effective

Question 17

What are the sources of antibiotic resistence genes?

Answer 17

-Plasmids: Lots of circular DNA, often carry multiple AB resistence genes, selection for one maintains resistence to all
-Transposons: integrate into chromosomal DNA. Allow transfer of genes from plasmid to chromosome
+vice versa
-Naked DNA. DNA from dead bacteria released into environment
-horizontal gene transfer allows rapid spread.
-Transformation (uptake of extracellular DNA)
-Conjugation ( DNA trasfer via pilus)
-Transduction ( DNA transfer using a virus as a vector to non offspring bacterium)

Question 18

What are non-genetic mechanisms of resistence?

Answer 18

• biofilm
• intraceulluar location
• slow growth
• spores
• persisters

Question 19

Summarise some of the main approaches used to prevent the emergence of drug-resistant bacteria and nosocomial infections

Answer 19

Better prescribing practices. Infection control. Combination therapy. Narrow vs broad spectrum antibiotic therapy

Question 20

when does antibiotic resistance emerge/

Answer 20

resistance typically emerges soon after the arrival of a new antibiotic.