antibiotic resistance

Question 1

define resistance

Answer 1

when a previously susceptible organism is no longer inhibited by an antibiotic at levels that can be safely achieved clinically

Question 2

define intermediate resistance

Answer 2

this is resistance that can be treated with an increase from the standard dose

Question 3

define therapeutic index

Answer 3

Difference between dose necessary for treatment, and minimum dose causing harm.

Question 4

Define minimum inhibitor concentration (MIC) + minimum bactericidal concentration (MBC).

Answer 4

Lowest concentration of an antibiotic that completely inhibits the growth of a bacterium.

Lowest concentration of an antibiotic that completely kills a bacterium.

Question 5

What is the MBC of bacteriostatic drugs ?

Answer 5

They do not have one (they do not kill the bacteria)

Question 6

Define antibiotic breakpoint.

What factors might change the antibiotic breakpoint.

Answer 6

-The antibiotic break point is the Concentration chosen for laboratory tests which will differentiate sensitive from resistant populations of bacteria (makes it easier for labs, allows them to test only one concentration rather than having to determine the MIC)

-The breakpoint of a given antibiotic will be different for different species because they will have different intrinsic resistance/susceptibility.

Question 7

what 3 factors will determine the breakpoint of the antibiotic?

Answer 7

• the distribution of the MICs of the target bacteria
• achievable therapeutic concentration in tissue
• maximum achievable concentration

Question 8

what is streptococci resistant to and why?

Answer 8

Streptococci are naturally resistant to aminoglycosides because their MIC is higher than the toxic concentration

Question 9

what is pseudomonas spp. naturally resistant to and why?

Answer 9

Pseudomonas spp. normally resistant to beta-lactams because intrinsic beta lactamases, although these can be overcome by design

Question 10

what is mycoplasma spp. naturally resistant to and why?

Answer 10

resistant to all beta lactams because the cell has has no peptidoglycan which beta lactams act against

Question 11

what is enterobaceriaciae naturally resistant to and why?

Answer 11

Enterobacteriacae are all resistant to metronidazole because they are facultative anaerobes, so normally grow in aerobic conditions

Question 12

define acquired resistance?

Answer 12

this occurs when a previously susceptible strain or species develops an increase in the MIC that takes it beyond the therapeutic range.

Question 13

what are the 6 main mechanisms of resistance?

Answer 13

1) enzymatic inactivation
2) enzymatic addition
3) impermeability
4) efflux
5) alternative pathways
6) altered target

Question 14

Identify an enzyme responsible for the process of enzymatic inactivation by destruction.

Answer 14

Beta lacatamases
Expanded spectrum beta lactamases

Beta lactams (including cephalosporins) are effected by this.

Question 15

what class of antibiotics affected by the process of enzymatic inactivation by addition.

Answer 15

aminoglycosides

Question 16

Describe the process of efflux. Identify an antibiotic affected by the process by efflux.

Answer 16

somebacteria will have efflux pumps which will extrude the toxic substance from the inside the bacteria (in this case the toxic substance is the antibiotic)
Mechanism of resistance which may have a role in organisms gaining higher levels of resistance.

Affects tetracyclines, quinolones, macrolides.

Question 17

Describe the process of alternative pathway.

Identify an antibiotic affected by this mechanism of resistance.

Answer 17

Some bacteria may bypass the route acted upon by the antibiotic and result in the same product via another pathway.

Meticillin (with MRSA)

Question 18

Describe the process of altering target.
Identify an antibiotic affected by this mechanism of resistance.

Answer 18

Alterations in the binding site of the target molecule result in an inability for the antibiotic to bind.

Rifampicin, fluoroquinolones, sulphonamides are all affected.

Question 19

What is the mechanism of action of fluoroquinolones.
How can their activity be reduced ?

Answer 19

binding and inhibiting DNA gyros to inhibit DNA supercoil

reduced binding to DNA by DNA gyros, results in resistance to quinolones.

Question 20

In general, how does resistance arise ? Give examples

Answer 20

Resistance arises through mutations in critical chromosomal genes (which are involved with the target of the antibiotic).

For instance rifampicin, DNA gyrases.

Question 21

Describe the evolution of resistance in quinolones (including the genes involved).

Answer 21

Two genes involved: gyrA and parC
Point mutations in these genes result in changes in the affinity of the proteins for DNA
Mutation in one gene encodes low level resistance where as in both it encodes high level resistance.

Question 22

Identify the most active fluoroquinolone against 1st and 2nd step mutants.

Answer 22

gemifloxacin

Question 23

Identify the main mechanisms of resistance transmission.
Give an example of antibiotic affected by each.

Answer 23

Transformation (e.g. penicillin)

Conjugation (e.g. B-lactamases)

Transposons (e.g. erythromicin)

Question 24

Describe the process of transformation for transmission of resistance.
Identify an antibiotic and pathogen for which this applies.

Answer 24

Bacterium takes up naked DNA from its environment into its own nucleus (through homologous recombination, forming mosaic gene).
If the naked DNA has a resistance gene mutation, the organism becomes resistant.

Neisseria gonorrhea and penicillin

Question 25

Describe the process of conjugation for transmission of resistance.

Answer 25

• one bacterium acts as the donor of the genetic material and another acts as the recipient
• donor bacteria transfers genetic material to the recipient in the form of a plasmid
• this genetic material can encode virulence, metabolic functions and resistance determinants.

Question 26

Describe the process of transposons for the transmission of resistance.

Answer 26

• transposons= small segments of dna that encode their own transmission
• any bacteria have these mobile genetic elements
• allows genome plasticity
• may collect resistance determinants.

Question 27

Define the term superbug.

Answer 27

Organism that has gained resistance to a critical antibiotic or organism that has gained resistance to multiple antibiotics.

Question 28

an example of a superbug? ?

Answer 28

MRSA- resistant to methicillin

Question 29

To what extent are most bacteria susceptible to Carbapenams ?

Answer 29

Most bacteria ARE susceptible to Carbapenams BUT new resistant stains (especially Enterobacteriaceae) containing following enzymes: Klebsiella Pneumoniae carbapenamase (KPC) or New Delhi metallo-betalactamase (NDM) or Oxa-48 carbapenemase.

Question 30

Why do we worry about resistance in some organisms and not others?

Answer 30

1) When the consequences of infection are severe and the organism is common

2) When the organism is naturally resistant to many antibiotics

3) When the infection is in a site where it is difficult to get high concentrations of antibiotic

Question 31

How do we address the problem of antibiotic resistance

Answer 31

-Optimise the treatment of bacterial disease
-Better diagnosis
-Focused treatment
-Appropriate length of courses

Question 32

What is the treatment for resistant bugs ?

Answer 32

-Culture + susceptibility testing
-Use most bactericidal drug available
-Consider use of combinations