antibiotic resistance Flashcards

1
Q

define resistance

A

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

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2
Q

define intermediate resistance

A

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

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3
Q

define therapeutic index

A

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

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4
Q

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

A

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

Lowest concentration of an antibiotic that completely kills a bacterium.

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5
Q

What is the MBC of bacteriostatic drugs ?

A

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

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6
Q

Define antibiotic breakpoint.

What factors might change the antibiotic breakpoint.

A

-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.

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7
Q

what 3 factors will determine the breakpoint of the antibiotic?

A
  • the distribution of the MICs of the target bacteria
  • achievable therapeutic concentration in tissue
  • maximum achievable concentration
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8
Q

what is streptococci resistant to and why?

A

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

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9
Q

what is pseudomonas spp. naturally resistant to and why?

A

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

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10
Q

what is mycoplasma spp. naturally resistant to and why?

A

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

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11
Q

what is enterobaceriaciae naturally resistant to and why?

A

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

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12
Q

define acquired resistance?

A

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

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13
Q

what are the 6 main mechanisms of resistance?

A

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

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14
Q

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

A

Beta lacatamases
Expanded spectrum beta lactamases

Beta lactams (including cephalosporins) are effected by this.

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15
Q

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

A

aminoglycosides

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16
Q

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

A

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.

17
Q

Describe the process of alternative pathway.

Identify an antibiotic affected by this mechanism of resistance.

A

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

Meticillin (with MRSA)

18
Q

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

A

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

Rifampicin, fluoroquinolones, sulphonamides are all affected.

19
Q

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

A

binding and inhibiting DNA gyros to inhibit DNA supercoil

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

20
Q

In general, how does resistance arise ? Give examples

A

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

For instance rifampicin, DNA gyrases.

21
Q

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

A

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.

22
Q

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

A

gemifloxacin

23
Q

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

A

Transformation (e.g. penicillin)

Conjugation (e.g. B-lactamases)

Transposons (e.g. erythromicin)

24
Q

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

A

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

25
Q

Describe the process of conjugation for transmission of resistance.

A
  • 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.
26
Q

Describe the process of transposons for the transmission of resistance.

A
  • transposons= small segments of dna that encode their own transmission
  • any bacteria have these mobile genetic elements
  • allows genome plasticity
  • may collect resistance determinants.
27
Q

Define the term superbug.

A

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

28
Q

an example of a superbug? ?

A

MRSA- resistant to methicillin

29
Q

To what extent are most bacteria susceptible to Carbapenams ?

A

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.

30
Q

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

A

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

31
Q

How do we address the problem of antibiotic resistance

A

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

32
Q

What is the treatment for resistant bugs ?

A

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