Choice of and Resistance to Antibiotics

Question 1

Describe and give examples of Intrinsic resistance to antibiotics

Answer 1

• Intrinsic  innate ability to resist activity of a particular antimicrobial agent through inherent structural or functional characteristics allowing tolerance to the drug e.g. poor membrane permeability, differences in and lack of targets

Question 2

Describe and give examples of Acquired resistance to antibiotics

Answer 2

• Acquired  when a microorganism obtains the ability to resist the activity of a drug and acquisition allows drug alteration, target alteration, bypass mechanism or efflux systems e.g. mutations that lead to loss of genes, modification of current ones and modification of expression levels

Question 3

Name four antibiotic resistance genes that bacteria can acquire

Answer 3

 Beta-lactamases (Breaks structure)
 Aminoglycoside modifying enzymes (Add modifications)
 Target site modifying enzymes (add modifications)
Efflux systems (new gene or upregulation of existing gene allows removal of drug from the cell so that it cannot reach an effective concentration

Question 4

Name and describe the two bacterial genetic resistance mechanisms

Answer 4

• Change in genetic makeup  New genes, loss of genes modification of gene function and modification of promotors
• Transferrable acquired Resistance  Tends to be based on plasmid genetic transfer

Question 5

Discuss how bacterial antibiotic resistance can be propogated in an environment

Answer 5

• Selective pressure will lead to development of resistant populations from resistant individuals
• Some genes may be closely linked so get co-selected in the absence of one other drug

Question 6

Describe MDR

Answer 6

• MDR (Multi Drug Resistance)  Acquired non susceptibly to at least one agent in three or more categories

Question 7

Describe XDR

Answer 7

• XDR (Extensively Drug Resistant)  Acquired non susceptibility to at least one agent in all but two or fewer antimicrobial categories

Question 8

Describe PDR

Answer 8

• PDR (Pan Drug Resistant) Acquired non susceptibility to all agents in all microbial categories

Question 9

Describe the role of plasmids in antibiotic resiatance

Answer 9

• Plasmids allow transfer of resistance between closely related bacteria and transfers of complex collections of genes to express resistances

Question 10

Describe prophylactic treatment and its effectiveness

Answer 10

Prophylactic Treatment - Use of antibiotics in the attempt to prevent an infection
Advantage is minimal if therapy commenced later than 3 hours after contamination , disadvantages include toxicity, encouragement of resistance, residues in food animals, cost

Question 11

Describe how you would select an antibiotic

Answer 11

• Form definitive diagnosis
• Perform gram staining to determine target/bacterial group
• Ideally perform sensitivity test (if haent before treatment mandatory to do this if initial treatment fails)

Question 12

In what circumstances is combination therapy useful and what are its risks

Answer 12

• Only in certain circumstances (mixed infections, severe conditions with unknown aetiology, life threatening cases, treating unusual pathogens)
• Drugs may be antagonistic or become problematic due to different pharmacokinetic factors
• Increased cost and risk of toxicity

Question 13

Which drugs do not work well for combination therapy?

Answer 13

Bacteriostatic and bacteriocidal drugs in combination.

Question 14

Describe adjunctive treatment

Answer 14

Adjunctive Treatment  Application of other supportive therapy e.g. fluid, surgery, drugs to improve effectiveness e.g. modify urine pH)

Question 15

What tests can be used to ascertain the MIC of a bacterial sample

Answer 15

Dilution and E-strip diffusion tests

Question 16

Define MIC

Answer 16

• MIC (Minimum Inhibitory Concentration)  Minimum Concentration of the antibiotic which will inhibit the growth of a bacteria

Question 17

Define MBC

Answer 17

• MBC (Minimum Bacterial Concentration)  Lowest concentration which will kill a bacterial strain (definition of killing being 99%)

Question 18

Describe quality control aspects for disk diffusion tests

Answer 18

Agar too thin/too thick
Too heavy inoculum
Mixed culture

Question 19

Describe distribution of resistance

Answer 19

• Most likely to get a clear separation between susceptible and resistance
• Some resistances can be stripwise with a number of grades e.g. sequential mutation to target ribosome can lead to further resistance

Question 20

Describe Break point assays

Answer 20

• Distinct from sensitivity tests
• Relies of the distinct separation of resistance and susceptibility
• Antibiotics in plates
• Number of strains tested on plates
• Control plate with no antibiotic