14. Quinolones and fluoroquinolones

Question 1

What is the MOA of Quinolones + Fluoroquinolones?

Answer 1

1. They inhibit topoisomerase II and IV → bactericidal + long post-abx effect.
2. Have concentration-dependent effect.
3. Resistance is common, so also given for long duration, thus considered “concentration and time dependent”.

Question 2

List the Quinolones.

Answer 2

1. Nalidixic acid (0th generation).

Question 3

What are the indications for quinolones and fluoroquinolones?

Answer 3

1. UTI - earlier gens if uncomplicated; cipro and levo for Pseudomonas, etc.
2. Pyelonephritis - also cipro + levo
3. Osteomyelitis - later gens with good bone penetration (Salmonella)
4. Prostatitis - good penetration
5. GI infections - Shigella, Salmonella, E. coli, Campylobacter
6. IC infections - Mycoplasma, Legionella, etc.; 3rd/4th gen “respiratory fluoroquinolones”
7. 2nd line anti-TBC - cipro and levo

Question 4

What are the possible side effects of quinolones and fluoroquinolones therapy?

Answer 4

Well-tolerated

1. GI, CNS (headache, or worse in pre-existing neurologic disease)
2. Tendon rupture - use ↑ risk of achilles rupture; especially in elderly or w/ corticosteroids
3. Cartilage damage - not recommended in children less than 10.
4. Photosensitivity
5. (Prolonged QT → TdP)

Question 5

What spectrum does Moxifloxacin cover?

Answer 5

It has a similar spectrum to levo, with even better Staph, incl. MRSA and anaerobes (B. frag) can be a monotherapy for polymicrobial infection!

Question 6

What spectrum does Levofloxacin cover?

Answer 6

Still good Gram -, less Pseudo, stronger for Staph, Strep + IC (Mycoplasma, Legionella, Mycobacterium, etc.)

Question 7

What is the resistance mechanism behind resistance to quinolones and fluoroquinolones in bacteria?

Answer 7

Resistance is by binding site alteration.

Question 8

What spectrum does Ofloxacin + Ciprofloxacin cover?

Answer 8

Stronger Gram - plus Pseudomonas (esp. cipro!), Staph and ICs (and weak Strep)

Question 9

What spectrum does Pefloxacin cover?

Answer 9

Good for Gram - , mild effect for other previous + Staph.

Question 10

How are the 2nd generation fluoroquinolones pharmacokinetics?

Answer 10

1. 2nd gen onward = better distribution → IC, bone, etc. (but not CNS!)
2. Metabolized in liver
3. Excreted in bile + kidney. Ofloxacin only eliminated by kidney. (↓ dose in renal disease).

Question 11

What spectrum does Norfloxacin cover?

Answer 11

Stronger Gram - effect plus Serratia, Enterobacter, Acinetobacter (weakly) + weak Pseudomonas effect.

Question 12

What interactions do quinolones and fluoroquinolones have?

Answer 12

CYP inhibition - mainly affects xanthine derivative metabolism, like caffeine (→ tachycardia).

Question 13

What are the indications for fluoroquinolones?

Answer 13

5 generations: quinolones → fluoroquinolones

• 1st gen: for GI + simple UTI
• 2nd gen: more commonly used in UTI
• 3rd and 4th gen: are called respiratory fluoroquinolones

Question 14

What are the kinetics like for quinolones and fluoroquinolones?

Answer 14

1. All can be oral (and parenteral admin is possible from 2nd gen onward)
2. Are chelators (Ca, Mg, Fe alter absorption), but less so than tetracyclines, so should not be taken with milk or antacids.

Question 15

What are the differences in generations of Fluoroquinolones?

Answer 15

Improved kinetics + spectrum as generations progress.

Question 16

What spectrum does Quinolones cover?

Answer 16

Gram-negative:

1. E. coli
2. H. flu
3. Salmonella
4. Shigella
5. Klebs

Question 17

List the Fluoroquinolones in order of generations.

Answer 17

1. Norfloxacin (1st gen)
2. Pefloxacin (2nd gen)
3. Ofloxacin + Ciprofloxacin (2nd gen)
4. Levofloxacin (3rd gen , “respiratory fluoroquinolones”)
5. Moxifloxacin (4th gen, “respiratory fluoroquinolones”)

Question 18

What are the indications for Norfloxacin?

Answer 18

Quinolones and 1st gen fluoroquinolones only for GI and UTI, don’t reach therapeutic levels elsewhere.