Anti-microbial Therapies 1- Prokaryotes And Eukaryotes (12)

Question 1

What are beta-lactams?

Answer 1

• group of antibiotics
• e.g. penicillin and methicillin
• interfere w/ synthesis of peptidoglycan component of bacterial cell wall
• bind to penicillin-binding proteins (PBPs)–> enzymes involved in peptidoglycan synthesis

Question 2

What is an antibiotic?

Answer 2

an antimicrobial agent produced by a microorganism that kills or inhibits other microorganisms

Question 3

What is an anti-microbial?

Answer 3

chemical that selectively kills or inhibits microbes (bacteria, fungi, viruses)

Question 4

What is minimal inhibitory concentration (MIC)?

Answer 4

the lowest conc. of AB needed to inhibit bacterial growth

Question 5

Why does routine use of antibiotics lead to resistance?

Answer 5

it provides a selective pressure for the acquisition and maintenance of resistance genes (N.B. natural selection–> resistant mutants outcompete others)

Question 6

What are the downsides of antibiotic resistance?

Answer 6

• increased time to find effective therapy
• need additional approaches e.g. surgical drainage
• newer drugs= expensive
• need to use more toxic drugs e.g. vancomycin
• need to use less effective 2nd choice ABs

Question 7

What are the major AB resistant bacterial pathogens?

Answer 7

Gram -ve
- Pseudomonas aeruginosa
- E.coli
- Salmonella spp.
- Acinetobacter abumannii
- Neisseria gonorrhoeae
Gram +ve
Staphylococcus aureus
Streprococcus pneumoniae
- Clostridium difficile
- Enterococcus spp
- Mycobacterium tuberculosis

Question 8

What is an aminoglycoside?

Answer 8

• e.g. gentamicin, streptomycin
• bactericidal
• target protein synthesis, RNA proofreading and cause damage to cell membrane
• v toxic, but inc. use due to resistance to other ABs

Question 9

What is rifampicin?

Answer 9

• bactericidal
• targets RNA polymerase
• spontaneous resistance is frequent
• secretions turn red–> affects compliance

Question 10

What is vancomycin?

Answer 10

• bactericidal
• targets bacterial cell wall: lipid 2 component of biosynthesis and D-ala residues in wall crosslinking
• v toxic, but inc. use due to resistance to other ABs

Question 11

What is linezolid?

Answer 11

• bacteriostatic
• gram +ve spectrum
• inhibits protein synthesis

Question 12

What is daptomycin?

Answer 12

• bactericidal
• targets bacterial cell membrane
• gram +ve
• toxicity limits dose

Question 13

What allows safe targeting and selective toxicity?

Answer 13

the large number of differences between mammals and bacteria

e.g. peptidoglycan biosynthesis, different molecules for protein synthesis etc…

Question 14

What are the 4 mechanisms of antibiotic resistance?

Answer 14

• altered target site structure e.g. MRSA encodes an alternative PBP (2a) w/ low affinity for beta-lactams
• inactivation of AB e.g. beta-lactamase
• altered metabolism e.g. inc. production of enzyme substrate can outcompete AB inhibitor
• decreased drug accumulation by pumping AB out of bacterial cell, so drug doesn’t reach effective conc.

Question 15

What are macrolides?

Answer 15

• e.g. erythromycin, azithromycin
• gram +ve and -ve infections
• targets protein synthesis through 50S ribosomal subunit

Question 16

What are quinolones?

Answer 16

• synthetic, broad spectrum, bactericidal

- target DNA gyrase in gram -ve and topoisomerase in gram +ve

Question 17

What are sources of antibiotic resistance genes?

Answer 17

• plasmids–> circular DNA, often carry multiple AB resistance genes–> if one is needed, bacterium keeps all
• transposons–> integrate into chromosomal DNA–> allow transfer of genes from plasmid to chromosome and vice versa
• naked DNA released from dead bacteria

Question 18

By what mechanisms can AB resistance genes be shared between bacteria?

Answer 18

• transformation: uptake of extracellular DNA
• conjugation: pilus-mediated DNA transfer
• transduction: phage-mediated DNA transfer

Question 19

What are some non-genetic mechanisms of resistance?

Answer 19

• biofilm
• hiding intracellularly
• slow growth
• spores e.g. C.difficile
• persisters (don’t replicate)

Question 20

What are other reasons for AB treatment failure?

Answer 20

• inappropriate choice for organism
• poor penetration of AB into target site
• inappropriate dose
• inappropriate administration
• presence of AB resistance within commensal flora (normal bacteria)

Question 21

What are some hospital-acquired infections?

Answer 21

• MRSA
• VISA
• Clostridium difficile
• VRE
• ESBL/NDM-1
• P.aeruginosa
• Acineterbacter baumannii
• Stenotrophomonas maltophilia

Question 22

What are risk factors for HAI?

Answer 22

• high number of ill people (immunosuppression)
• crowded wards
• presence of pathogens
• broken skin
• indwelling devices e.g. intubation
• AB therapy may suppress normal flora (so no competition)
• transmission by staff (contact w/ multiple patients)

Question 23

How do we address AB resistance?

Answer 23

• prescribing strategies: tighter controls, temporary withdrawal of certain classes
• reduce use of broad-spectrum ABs
• quicker identification of infections caused by resistant strains
• combination therapy
• knowledge of local strains/resistance patterns

Question 24

How do we overcome resistance?

Answer 24

• modification of existing medications

- combinations of AB and inhibitor e.g. e.g. beta-lactamase inhibitors