Fluoroquinolones Flashcards
What are Fluoroquinolones?
- The most recent class of antibiotic drugs (1989)
- Unique mechanism of action
- Tend to have long half-lives and excellent oral bioavailability, making them convenient to take → the reason this second-line class has been heavily used first-line
- was second line because bacteria developed resistance and had adverse side effects
- Generic names end in “-floxacin”
- Example: Ciprofloxacin
Fluoroquinolone mechanism of action
- When bacteria replicate and/or undergo transcription, they must relax/cleave their chromosomal DNA so that recoiling and reading of genes can occur
- Topoisomerases (including DNA gyrase) re-attach the cleaved ends during supercoiling
- Fluoroquinolones inhibit this re-attachment → chromosomes become fragmented → leads to cell death
- damages DNA = bactericidal drugs
What is ciprofloxacin? spectrum of activity and what is it effective against?
- Used to treat respiratory infections, soft tissue/bone infections, typhoid, anthrax
- Spectrum of activity: Similar to gentamicin (an AG)
- Effective against Gram negative (have protective LPS layer so they are harder to treat - good we have another drug that can do it) aerobes, some Gram positive aerobes (including Staph), and atypical bacteria
- Ciprofloxacin is ineffective against anaerobes
Pharmacokinetics of fluoroquinolones
- Oral bioavailability approaches 100% → absorbed quickly from GIT which doesn’t cause GI issues
- Long half-lives
- Ciprofloxacin ~4 h → really good only have to administer once a day
- Moxifloxacin~10h - Concentrate in lung
- Renal excretion
- resistance to fluoroquinolones also causes resistance to other drugs
Adverse effects of fluoroquinolones
- Cartilage damage: Severe in young animals & humans
(humans are less sensitive to this effect than dogs, rabbits, etc.)
- In general, avoid if <18y old, pregnant, nursing - Tendon rupture: Rupture or tendonitis may occur in adults (e.g., Achilles tendon rupture)
- Cause a reduction of the seizure threshold like beta-lactams
- Other CNS effects also possible, e.g., headache, dizziness - Phototoxicity: Avoid excessive sunlight exposure
Fluoroquinolones resistance
- Main mechanism: Mutations in bacterial chromosomal genes
coding for DNA gyrases/topoisomerases that inhibit FQ binding - Some mutations confer resistance to one drug, some confer
resistance to all fluoroquinolones - FYI: Other mechanisms of resistance are plasmid-encoded (ie. Efflux pumps, gyrase protection proteins) and can confer resistance to other non-FQ drugs…
- These genes are often contained on the same plasmids that carry beta-lactamases and sometimes many other resistance genes
Acquired resistance to the tetracyclines is most commonly mediated by a plasmid-encoded:
a) Penicillinase
b) Transpeptidase
c) Altered version of dihydropteroate synthetase
d) Efflux pump
e) Ribosomal protection protein
a) Penicillinase - resistance to penicillin
b) Transpeptidase - builds peptidoglycan layer
c) Altered version of dihydropteroate synthetase - sulfonamides
d) Efflux pump ✓
e) Ribosomal protection protein
Which of the following statements most accurately describes the GENERAL spectrum of activity of penicillin G?
a) Most Gram-positive aerobes + most anaerobic bacteria
b) Most Gram-positive aerobes + most anaerobic bacteria plus many medically important Gram-negative aerobes
c) Most atypical bacteria
d) Most Gram-negative aerobes + mycoplasma but no anaerobic bacteria
a) Most Gram-positive aerobes + most anaerobic bacteria ✓
b) Most Gram-positive aerobes + most anaerobic bacteria plus many medically important Gram-negative aerobes - amoxycillin and 1st gen cephalosporins
c) Most atypical bacteria - tetracyclines
d) Most Gram-negative aerobes + mycoplasma but no anaerobic bacteria - aminoglycosides
Which of the following drugs would be most effective in the treatment of an anaerobic bacterial infection?
a) Tetracycline
b) TMS (Trimethoprim-sulfamethoxazole)
c) Penicillin G
d) Gentamicin
a) Tetracycline - gram + and gram -
b) TMS (Trimethoprim-sulfamethoxazole) - atypical
c) Penicillin G ✓
d) Gentamicin - aminoglycosides
A dehydrated patient is LEAST likely to sustain significant renal damage from the administration of:
a) TMS
b) Gentamicin
c) Cephalexin
d) Oxytetracycline
a) TMS - given to dehydrated patient can cause significant damage
b) Gentamicin - AG - renal damage
c) Cephalexin ✓
d) Oxytetracycline - tetracyclines also cause renal damage
You have made a diagnosis of Chlamydial conjunctivitis in an otherwise-healthy 4-year- old male castrated cat.
Which of the following antimicrobials would be most appropriate for the topical treatment of this infection?
a) Gentamicin b) Tetracycline c) Amoxicillin d) Enrofloxacin e) Cephalexin
a) Gentamicin - aminoglycoside
b) Tetracycline ✓
c) Amoxicillin - beta-lactam
d) Enrofloxacin - beta-lactam - second line treatment
e) Cephalexin - beta-lactam
