Quinolone Antimicrobial Agents

Question 1

First generation quinolones

• activity
• when are they useful

Answer 1

Activity against Gram-(–) bacteria
They have limited activity vs. Gram-(+) bacteria.

They do not achieve useful systemic concentrations and are only useful for treatment of lower urinary tract infections.

Question 2

What are the first generation quinolones?

Answer 2

Oxolinic acid

Nalidixic acid

Question 3

Second generation quinolones

• structure
• spectrum of activity/potency
• examples of activity of these
  
  • –Norfloxacin and levofloxacin
  • –Ciprofloxacin

Answer 3

Have a fluorine substituent at C-6 and a heterocyclic ring (usually piperazine) at C-7.

They have a broader spectrum of bactericidal activity and are more potent.

Norfloxacin and levofloxacin show a 40-100 fold increase in potency over nalidixic acid against most Gram-(–) species including Pseudomonas sp

Ciprofloxacin is the most potent fluoroquinolone for Gram-(–) organisms.

These drugs have extended activity against Gram-(+) organisms and Mycoplasma.

Question 4

What are the second generation quinolones?

Answer 4

Norfloxacin
Ciprofloxacin
Levofloxacin

Question 5

Review of action of DNA topoisomerases and gyrase

Answer 5

Gyrases and topoisomerases untangle the DNA during replication by cutting one (topoisomerase I) or two (topoisomerase II) strands, and then allowing strand passage through the break or allowing the DNA to twist

The topoisomerases and gyrases cleave DNA by carrying out a nucleophilic attack on a phosphodiester linkage