Antibiotic Resistance

Question 1

What is 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

How would you treat intermediate resistance?

Answer 2

increase of the standard dose

Question 3

What is the therapeutic index?

Answer 3

the difference between the dose necessary for treatment and the dose that causes harm

Question 4

What is intrinsic resistance?

Answer 4

When all strains of a species are naturally resistant

Question 5

What is MIC and MBC?

Answer 5

• MIC: minimum inhibitory concentration is the lowest concentration of an antibiotic that completely inhibits growth of bacterium
• MBC: minimum bactericidal concentration is the lowest dose that completely kills a bacterium (always higher than MIC)

Question 6

What is antibiotic breakpoint?

Answer 6

• concentration chosen for laboratory testing that will differentiate sensitive from resistant populations of bacteria
• varies for each species

Question 7

Why are antibiotic breakpoints used?

Answer 7

• to simplify testing

- to allow labs to test only one concentration rather than having to determine the MIC

Question 8

What defines antibiotic breakpoint?

Answer 8

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

Question 9

What are some examples of intrinsically resistant bacteria?

Answer 9

• streptococci are resistant to aminoglycosides (MIC > conc. that causes toxicity)
• pseudomonas spp. are resistant to B-lactams (produces B-lactamases)
• mycoplasma spp. resistant to all B-lactam antibiotics (has no effect as they do not have peptidolglycan)

Question 10

What is acquired resistance?

Answer 10

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

Question 11

What are the resistance mechanisms?

Answer 11

• enzymatic inactivation
• enzymatic addition
• impermeability
• efflux
• alternative pathway
• altered target

Question 12

What are examples of bacteria that become resistant by enzyme inactivation and their mechanism?

Answer 12

• hydrolyses it which inactivates it

- eg. B-lactamases, cephalosporins, and expanded spectrum B-lactamases

Question 13

What are examples of bacteria that become resistant by enzyme addition and their mechanism?

Answer 13

• adds adenylases/phosphorylases/acetylases which inactivates it
• eg. aminoglycosides

Question 14

What are examples of bacteria that become resistant by efflux pumps?

Answer 14

• tetracyclines
• quinolones
• macrolides
• can contribute to organisms gaining a higher level of resistance

Question 15

What are examples of bacteria that become resistant by alternative pathways and their mechanism?

Answer 15

• flucloxacillin

- precursors are converted to peptidoglycan through a Mec A product instead of through penicillin binding proteins

Question 16

What are examples of bacteria that become resistant by an altered binding site?

Answer 16

• rifampicin
• fluoroquinolones
• sulphonamides

Question 17

Describe the evolution of quinolone resistance

Answer 17

• 2 genes involved GyrA and parC
• point mutations change affinity of proteins for DNA
• mutation in one gene encodes low resistance
• mutation in both genes encodes high level resistance

Question 18

What are the resistance transmission mechanisms?

Answer 18

• transformation (altered gene with altered affinity for product eg. penicillin/S.pneumoniae)
• conjugation (plasmids shared between bacteria, can encode resistance determinants eg. B-lactamases)
• transposons (small segments of DNA that encode their own transmission that can collect resistance determinants eg. erythromycin in S.pyogenes)

Question 19

What is a superbug and examples?

Answer 19

• organism that has gained resistance to a critical antibiotic
• organism that has gained resistance to multiple antibiotics
• eg. MRSA/GISA/VRE

Question 20

What are the carbapenemases and their active sites?

Answer 20

• KPC (serine)
• NDM (zinc)
• Oxa-48 group (serine)

Question 21

Describe how carbapenemases cause resistance and the bacteria it is active against

Answer 21

• by transmission of plasmid (conjugation)
• KPC: cephalosporins/aztreonam/carbapenems
• NDM: cephalosporin/BL/BLI/carbapenems
• Oxa-48: 1-3rd generation cephalosporins, variable against 4th/BL/BLI/carbapenems

Question 22

When do we worry about resistant bacteria?

Answer 22

• when consequences of infection are severe and organism is common (MRSA)
• when organism is naturally resistant to many antibiotics (Ps.aeruginosa)
• when the infection is in a site where it is difficult to get high concentrations of antibiotic (pneumococcal meningitis)

Question 23

How is bacterial resistance addressed?

Answer 23

• optimise treatment of bacterial disease
• better diagnostics/diagnosis
• focused treatment
• appropriate length of courses

Question 24

How are resistant bugs treated?

Answer 24

• culture
• susceptibility testing
• use most bactericidal drug available
• consider use of combinations